Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.

PubMed

Garjani, Alireza; Andalib, Sina; Biabani, Sajjad; Soraya, Hamid; Doustar, Yousef; Garjani, Afagh; Maleki-Dizaji, Nasrin

2011-09-01

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration. Copyright © 2011 Elsevier B.V. All rights reserved.

Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

PubMed

Robinson, Reeder; Franceschini, Stefano; Fedkenheuer, Michael; Rodriguez, Pedro J; Ellerbrock, Jacob; Romero, Elvira; Echandi, Maria Paulina; Martin Del Campo, Julia S; Sobrado, Pablo

2014-04-01

Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the KD values, as no major changes on the kcat or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP⁺ in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

PubMed

Ghanbarzadeh, S; Garjani, A; Ziaee, M; Khorrami, A

2014-09-01

Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

PubMed Central

Sun, Jiao; Wang, Fan; Sui, Yue; She, Zhennan; Zhai, Wenjun; Wang, Chunling; Deng, Yihui

2012-01-01

In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold. PMID:23166438

Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency

PubMed Central

Pierrel, Fabien

2017-01-01

Coenzyme Q is a lipid that participates to important physiological functions. Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q10 supplementation of patients is the classical treatment but it shows limited efficacy in some cases. The molecular understanding of the coenzyme Q biosynthetic pathway allowed the design of experiments to bypass deficient biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide the defective chemical group and can reactivate endogenous coenzyme Q biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and mouse models of primary coenzyme Q deficiency. This mini review presents how the chemical properties of various analogs of 4-hydroxybenzoic acid dictate the effect of the molecules on CoQ biosynthesis and how the reactivation of endogenous coenzyme Q biosynthesis may achieve better results than exogenous CoQ10 supplementation. PMID:28690551

Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency.

PubMed

Pierrel, Fabien

2017-01-01

Coenzyme Q is a lipid that participates to important physiological functions. Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q 10 supplementation of patients is the classical treatment but it shows limited efficacy in some cases. The molecular understanding of the coenzyme Q biosynthetic pathway allowed the design of experiments to bypass deficient biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide the defective chemical group and can reactivate endogenous coenzyme Q biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and mouse models of primary coenzyme Q deficiency. This mini review presents how the chemical properties of various analogs of 4-hydroxybenzoic acid dictate the effect of the molecules on CoQ biosynthesis and how the reactivation of endogenous coenzyme Q biosynthesis may achieve better results than exogenous CoQ 10 supplementation.

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

PubMed

Salles, João Eduardo; Moisés, Valdir A; Almeida, Dirceu R; Chacra, Antonio R; Moisés, Regina S

2006-04-01

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Requirement for Coenzyme Q in Plasma Membrane Electron Transport

NASA Astrophysics Data System (ADS)

Sun, I. L.; Sun, E. E.; Crane, F. L.; Morre, D. J.; Lindgren, A.; Low, H.

1992-12-01

Coenzyme Q is required in the electron transport system of rat hepatocyte and human erythrocyte plasma membranes. Extraction of coenzyme Q from the membrane decreases NADH dehydrogenase and NADH:oxygen oxidoreductase activity. Addition of coenzyme Q to the extracted membrane restores the activity. Partial restoration of activity is also found with α-tocopherylquinone, but not with vitamin K_1. Analogs of coenzyme Q inhibit NADH dehydrogenase and oxidase activity and the inhibition is reversed by added coenzyme Q. Ferricyanide reduction by transmembrane electron transport from HeLa cells is inhibited by coenzyme Q analogs and restored with added coenzyme Q10. Reduction of external ferricyanide and diferric transferrin by HeLa cells is accompanied by proton release from the cells. Inhibition of the reduction by coenzyme Q analogs also inhibits the proton release, and coenzyme Q10 restores the proton release activity. Trans-plasma membrane electron transport stimulates growth of serum-deficient cells, and added coenzyme Q10 increases growth of HeLa (human adenocarcinoma) and BALB/3T3 (mouse fibroblast) cells. The evidence is consistent with a function for coenzyme Q in a trans-plasma membrane electron transport system which influences cell growth.

Dexpanthenol enemas in ulcerative colitis: a pilot study.

PubMed

Loftus, E V; Tremaine, W J; Nelson, R A; Shoemaker, J D; Sandborn, W J; Phillips, S F; Hasan, Y

1997-07-01

To test the hypothesis that topical administration of pantothenic acid, a precursor of coenzyme A, might result in increased tissue levels of coenzyme A, improvement of fatty acid oxidation, and amelioration of ulcerative colitis. In an open-label pilot study, three patients with active left-sided ulcerative colitis received nightly enemas that contained 1,000 mg of dexpanthenol for 4 weeks. Before and after the study, patients submitted stool specimens for short-chain fatty acid analysis and urine collections for measurement of pantothenic acid and dicarboxylic acids; they also underwent flexible sigmoidoscopy for procurement of biopsy specimens for histologic examination and measurement of colonic coenzyme A activity. A clinical disease activity index and histologic disease activity index were used to assess response. Despite increases in urinary pantothenic acid, no significant changes were found in colonic tissue coenzyme A concentrations, fecal short-chain fatty acid concentrations, or urinary dicarboxylic acid concentrations. Moreover, no significant changes in clinical or histologic disease activity were noted. Although stool frequency and rectal bleeding remained unchanged, all patients noted increased abdominal cramping, and one patient had an increased extent of disease. Topically administered dexpanthenol seems to be absorbed, but at the dose used in this study, it did not influence concentrations of colonic coenzyme A activity, fecal short-chain fatty acids, or clinical response in patients with active left-sided ulcerative colitis.

Improved Xylitol Production from D-Arabitol by Enhancing the Coenzyme Regeneration Efficiency of the Pentose Phosphate Pathway in Gluconobacter oxydans.

PubMed

Li, Sha; Zhang, Jinliang; Xu, Hong; Feng, Xiaohai

2016-02-10

Gluconobacter oxydans is used to produce xylitol from D-arabitol. This study aims to improve xylitol production by increasing the coenzyme regeneration efficiency of the pentose phosphate pathway in G. oxydans. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were overexpressed in G. oxydans. Real-time PCR and enzyme activity assays revealed that G6PDH/6PGDH activity and coenzyme regeneration efficiency increased in the recombinant G. oxydans strains. Approximately 29.3 g/L xylitol was obtained, with a yield of 73.2%, from 40 g/L d-arabitol in the batch biotransformation with the G. oxydans PZ strain. Moreover, the xylitol productivity (0.62 g/L/h) was 3.26-fold of the wild type strain (0.19 g/L/h). In repetitive batch biotransformation, the G. oxydans PZ cells were used for five cycles without incurring a significant loss in productivity. These results indicate that the recombinant G. oxydans PZ strain is economically feasible for xylitol production in industrial bioconversion.

The structure of Medicago truncatula δ 1-pyrroline-5-carboxylate reductase provides new insights into regulation of proline biosynthesis in plants

DOE PAGES

Ruszkowski, Milosz; Nocek, Boguslaw; Forlani, Giuseppe; ...

2015-10-30

The two pathways for proline biosynthesis in higher plants share the last step, the conversion of δ 1-pyrroline-5-carboxylate (P5C) to L-proline, which is catalyzed by P5C reductase (P5CR, EC 1.5.1.2) with the use of NAD(P)H as a coenzyme. There is increasing amount of evidence to suggest a complex regulation of P5CR activity at the post-translational level, yet the molecular basis of these mechanisms is unknown. Here we report the three-dimensional structure of the P5CR enzyme from the model legume Medicago truncatula (Mt). The crystal structures of unliganded MtP5CR decamer, and its complexes with the products NAD +, NADP +, andmore » L-proline were refined using x-ray diffraction data (at 1.7, 1.85, 1.95, and 2.1 Å resolution, respectively). Based on the presented structural data, the coenzyme preference for NADPH over NADH was explained, and NADPH is suggested to be the only coenzyme used by MtP5CR in vivo. Moreover, the insensitivity of MtP5CR to feed-back inhibition by proline, revealed by enzymatic analysis, was correlated with structural features. Additionally, a mechanism for the modulation of enzyme activity by chloride anions is discussed, as well as the rationale for the possible development of effective enzyme inhibitors.« less

Longevity of major coenzymes allows minimal de novo synthesis in microorganisms.

PubMed

Hartl, Johannes; Kiefer, Patrick; Meyer, Fabian; Vorholt, Julia A

2017-05-15

Coenzymes are vital for cellular metabolism and act on the full spectrum of enzymatic reactions. Intrinsic chemical reactivity, enzyme promiscuity and high flux through their catalytic cycles make coenzymes prone to damage. To counteract such compromising factors and ensure stable levels of functional coenzymes, cells use a complex interplay between de novo synthesis, salvage, repair and degradation. However, the relative contribution of these factors is currently unknown, as is the overall stability of coenzymes in the cell. Here, we use dynamic 13 C-labelling experiments to determine the half-life of major coenzymes of Escherichia coli. We find that coenzymes such as pyridoxal 5-phosphate, flavins, nicotinamide adenine dinucleotide (phosphate) and coenzyme A are remarkably stable in vivo and allow biosynthesis close to the minimal necessary rate. In consequence, they are essentially produced to compensate for dilution by growth and passed on over generations of cells. Exceptions are antioxidants, which are short-lived, suggesting an inherent requirement for increased renewal. Although the growth-driven turnover of stable coenzymes is apparently subject to highly efficient end-product homeostasis, we exemplify that coenzyme pools are propagated in excess in relation to actual growth requirements. Additional testing of Bacillus subtilis and Saccharomyces cerevisiae suggests that coenzyme longevity is a conserved feature in biology.

Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model.

PubMed

El-Ganainy, Samar O; El-Mallah, Ahmed; Abdallah, Dina; Khattab, Mahmoud M; Mohy El-Din, Mahmoud M; El-Khatib, Aiman S

2016-06-01

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Profiling Redox and Energy Coenzymes in Whole Blood, Tissue and Cells Using NMR Spectroscopy.

PubMed

Gowda, G A Nagana

2018-05-14

Coenzymes of cellular redox reactions and cellular energy, as well as antioxidants mediate biochemical reactions fundamental to the functioning of all living cells. Conventional analysis methods lack the opportunity to evaluate these important redox and energy coenzymes and antioxidants in a single step. Major coenzymes include redox coenzymes: NAD⁺ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), NADP⁺ (oxidized nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate); energy coenzymes: ATP (adenosine triphosphate), ADP (adenosine diphosphate) and AMP (adenosine monophosphate); and antioxidants: GSSG (oxidized glutathione) and GSH (reduced glutathione). We show here that a simple ¹H NMR experiment can measure these coenzymes and antioxidants in tissue and whole blood apart from a vast pool of other metabolites. In addition, focused on the goal of identification of coenzymes in subcellular fractions, we demonstrate analysis of coenzymes in the cytoplasm using breast cancer cells. Owing to their unstable nature, or low concentrations, most of the coenzymes either evade detection or lose their integrity when established sample preparation and analysis methods are used. To overcome this challenge, here we describe the development of new methods to detect these molecules without affecting the integrity of other metabolites. We used an array of 1D and 2D NMR methods, chemical shift databases, pH measurements and spiking with authentic compounds to establish the identity of peaks for the coenzymes and antioxidants in NMR spectra. Interestingly, while none of the coenzymes and antioxidants were detected in plasma, they were abundant in whole blood. Considering that the coenzymes and antioxidants represent a sensitive measure of human health and risk for numerous diseases, the presented NMR methods to measure them in one step potentially open new opportunities in the metabolomics field.

Fine tuning of coenzyme specificity in family 2 aldo-keto reductases revealed by crystal structures of the Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD + and NADP +

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leitgeb, Stefan; Petschacher, Barbara; Wilson, David K.

2005-01-11

Aldo-keto reductases of family 2 employ single site replacement Lys → Arg to switch their cosubstrate preference from NADPH to NADH. X-ray crystal structures of Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD + and NADP + were determined at a resolution of 2.4 and 2.3 Å, respectively. Due to steric conflicts in the NADP +-bound form, the arginine side chain must rotate away from the position of the original lysine side chain, thereby disrupting a network of direct and water-mediated interactions between Glu-227, Lys-274 and the cofactor 2'-phosphate and 3'-hydroxy groups. Because anchoring contactsmore » of its Glu-227 are lost, the coenzyme-enfolding loop that becomes ordered upon binding of NAD(P) + in the wild-type remains partly disordered in the NADP +-bound mutant. The results delineate a catalytic reaction profile for the mutant in comparison to wild-type.« less

Coenzyme preference of Streptococcus pyogenes δ1-pyrroline-5-carboxylate reductase: evidence supporting NADPH as the physiological electron donor.

PubMed

Petrollino, Davide; Forlani, Giuseppe

2012-07-01

The streptococcal enzyme that catalyzes the last step in proline biosynthesis was heterologously expressed and the recombinant protein was purified to electrophoretic homogeneity and characterized thoroughly. As for δ1-pyrroline-5-carboxylate reductases from other sources, it was able to use either NADH or NADPH as the electron donor in vitro. However, with NADH the activity was markedly inhibited by physiological levels of NADP+. Results also strengthen the possibility that an unusual ordered substrate binding occurs, in which the dinucleotide binds last.

The production of coenzyme Q10 in microorganisms.

PubMed

Cluis, Corinne P; Pinel, Dominic; Martin, Vincent J

2012-01-01

Coenzyme Q10 has emerged as a valuable molecule for pharmaceutical and cosmetic applications. Therefore, research into producing and optimizing coenzyme Q10 via microbial fermentation is ongoing. There are two major paths being explored for maximizing production of this molecule to commercially advantageous levels. The first entails using microbes that naturally produce coenzyme Q10 as fermentation biocatalysts and optimizing the fermentation parameters in order to reach industrial levels of production. However, the natural coenzyme Q10-producing microbes tend to be intractable for industrial fermentation settings. The second path to coenzyme Q10 production being explored is to engineer Escherichia coli with the ability to biosynthesize this molecule in order to take advantage of its more favourable fermentation characteristics and the well-understood array of genetic tools available for this bacteria. Although many studies have attempted to over-produce coenzyme Q10 in E. coli through genetic engineering, production titres still remain below those of the natural coenzyme Q10-producing microorganisms. Current research is providing the knowledge needed to alleviate the bottlenecks involved in producing coenzyme Q10 from an E. coli strain platform and the fermentation parameters that could dramatically increase production titres from natural microbial producers. Synthesizing the lessons learned from both approaches may be the key towards a more cost-effective coenzyme Q10 industry.

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy.

PubMed

Cooper, J M; Korlipara, L V P; Hart, P E; Bradley, J L; Schapira, A H V

2008-12-01

A pilot study of high dose coenzyme Q(10) (CoQ(10))/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. Fifty FRDA patients were randomly divided into high or low dose CoQ(10)/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. At baseline serum CoQ(10) and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ(10) and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ(10) levels. A high proportion of FRDA patients have a decreased serum CoQ(10) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy. Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chloroplast 2010: A Database for Large-Scale Phenotypic Screening of Arabidopsis Mutants1[W][OA

PubMed Central

Lu, Yan; Savage, Linda J.; Larson, Matthew D.; Wilkerson, Curtis G.; Last, Robert L.

2011-01-01

Large-scale phenotypic screening presents challenges and opportunities not encountered in typical forward or reverse genetics projects. We describe a modular database and laboratory information management system that was implemented in support of the Chloroplast 2010 Project, an Arabidopsis (Arabidopsis thaliana) reverse genetics phenotypic screen of more than 5,000 mutants (http://bioinfo.bch.msu.edu/2010_LIMS; www.plastid.msu.edu). The software and laboratory work environment were designed to minimize operator error and detect systematic process errors. The database uses Ruby on Rails and Flash technologies to present complex quantitative and qualitative data and pedigree information in a flexible user interface. Examples are presented where the database was used to find opportunities for process changes that improved data quality. We also describe the use of the data-analysis tools to discover mutants defective in enzymes of leucine catabolism (heteromeric mitochondrial 3-methylcrotonyl-coenzyme A carboxylase [At1g03090 and At4g34030] and putative hydroxymethylglutaryl-coenzyme A lyase [At2g26800]) based upon a syndrome of pleiotropic seed amino acid phenotypes that resembles previously described isovaleryl coenzyme A dehydrogenase (At3g45300) mutants. In vitro assay results support the computational annotation of At2g26800 as hydroxymethylglutaryl-coenzyme A lyase. PMID:21224340

Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes.

PubMed

Knaus, Tanja; Paul, Caroline E; Levy, Colin W; de Vries, Simon; Mutti, Francesco G; Hollmann, Frank; Scrutton, Nigel S

2016-01-27

The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread exploitation. Stoichiometric use of natural coenzymes is not viable economically, and the instability of these molecules hinders catalytic processes that employ coenzyme recycling. Here, we investigate the efficiency of man-made synthetic biomimetics of the natural coenzymes NAD(P)H in redox biocatalysis. Extensive studies with a range of oxidoreductases belonging to the "ene" reductase family show that these biomimetics are excellent analogues of the natural coenzymes, revealed also in crystal structures of the ene reductase XenA with selected biomimetics. In selected cases, these biomimetics outperform the natural coenzymes. "Better-than-Nature" biomimetics should find widespread application in fine and specialty chemicals production by harnessing the power of high stereo-, regio-, and chemoselective redox biocatalysts and enabling reactions under mild conditions at low cost.

ANTAGONISTIC EFFECTS OF 6-MERCAPTOPURINE AND COENZYME A ON MITOCHONDRIA AND MITOSIS IN TISSUE CULTURE

PubMed Central

Biesele, John J.

1955-01-01

The partial mitotic inhibition caused by 6-mercaptopurine in tissue cultures of Crocker mouse sarcoma 180 and embryonic mouse skin is blocked by co-enzyme A. 6-Mercaptopurine and coenzyme A also have opposite effects on mitochondrial morphology. Mitochondria in cells treated with 6-mercaptopurine become thin and fragmented. Coenzyme A blocks this effect, and alone coenzyme A makes for longer and thicker mitochondria. 6-Mercaptopurine inhibits lipogenesis in embryo skin fibroblasts, and this inhibition is partly counteracted by coenzyme A, which by itself makes for a greater accumulation of lipid droplets in the cytoplasm. It is suggested that at least one part of the action by which 6-mercaptopurine decreases mitotic incidence in tissue cultures may be an interference on the part of 6-mercaptopurine, acting as an antimetabolite of coenzyme A, in mitochondrial function related to cell division. PMID:14381434

Combination Therapy with Glucan and Coenzyme Q10 in Murine Experimental Autoimmune Disease and Cancer.

PubMed

Vetvicka, Vaclav; Vetvickova, Jana

2018-06-01

Coenzyme Q 10 is a well-accepted anti-oxidant agent known to play a protective role in various physiological and disease processes. Recently, Coenzyme Q 10 is gaining attention as a substance with significant anti-inflammatory properties. β-Glucan is the most studied immunomodulator with significant synergetic effects with numerous bioactive molecules. We aimed to evaluate the possible synergistic effects of simultaneous use of coenzyme Q 10 with the well-established immune modulator, β-glucan, on immune reactions and cancer development. Coenzyme Q 10 and β-glucan were used, both in vivo and in vitro, and their effects were evaluated using phagocytosis and cytokine secretion. Our study confirmed the strong anti-inflammatory effects of coenzyme Q 10 and showed that these effects were further potentiated with the addition of β-glucan. The anticancer effects of coenzyme Q 10 were less pronounced, but stronger, with the addition of β-glucan. There is significant synergy between coenzyme Q 10 and β-glucan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study.

PubMed

Kędziora-Kornatowska, Kornelia; Czuczejko, Jolanta; Motyl, Jadwiga; Szewczyk-Golec, Karolina; Kozakiewicz, Mariusz; Pawluk, Hanna; Kędziora, Józef; Błaszczak, Robert; Banach, Maciej; Rysz, Jacek

2010-08-30

An increase in oxidative stress is strongly documented in hypertensive patients. In blood vessels, oxidative stress increases the production of superoxide anion (O(2) (•-)) that reacts with nitric oxide (NO) and impairs the ability of endothelium to relax. Many reports indicate a beneficial effect of coenzyme Q10 (CoQ) in hypertension. Coenzyme Q10 therapy may lower O(2) (•-) and thus decrease the complications associated with hypertension. The aim of our study was to evaluate the effects of CoQ supplementation on antioxidative enzyme activities and lipid peroxidation in elderly hypertensive patients. We determined the activities of superoxide dismutase (SOD-1) and glutathione peroxidase (GSH-Px) and the concentration of malondialdehyde (MDA) in erythrocytes of 27 elderly (mean age 72.5 ±6.1 year) hypertensive patients treated with indapamide at baseline and after 12 weeks of CoQ supplementation (60 mg twice a day) in comparison with 30 healthy elderly volunteers (mean age 76.8 ±8.5 year). Decrease of SOD-1 (p < 0.001) and insignificant reduction of GSH-Px activities and increase of MDA (p < 0.001) level were observed in hypertensive patients in comparison to healthy volunteers before supplementation. Coenzyme Q10 administration resulted in a significant increase only in SOD-1 activity (p < 0.001). The present study indicates that CoQ improves the most important component of the antioxidant defence system - SOD-1, which is responsible for O(2) (•-) scavenging. Coenzyme Q10 may be used as an additional therapeutic agent for prophylaxis and treatment of hypertension in elderly patients.

Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

PubMed

Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

2017-11-21

Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

PubMed Central

González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

2015-01-01

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

76 FR 42729 - Certain Coenzyme Q10 Products and Methods of Making Same; Notice of Institution of Investigation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-790] Certain Coenzyme Q10 Products and Methods of... United States after importation of certain coenzyme Q10 products and methods of making same by reason of... after importation of certain coenzyme Q10 products and methods of making same that infringe one or more...

Artificial Enzymes with Thiazolium and Imidazolium Coenzyme Mimics

PubMed Central

Zhao, Huanyu; Foss, Frank W.; Breslow, Ronald

2009-01-01

Hydrophobic thiazolium and imidazolium coenzyme mimics in the presence of modified-polyethylenimine enzyme mimics catalyze the benzoin condensation 2300–3300 times faster than the coenzyme mimics alone. Polycationic enzyme mimics provide not only a hydrophobic binding domain for coenzyme and substrate, but also electrostatic stabilization of anionic species that arise along the reaction pathway of the benzoin condensation. PMID:18763766

Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes

PubMed Central

2016-01-01

The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread exploitation. Stoichiometric use of natural coenzymes is not viable economically, and the instability of these molecules hinders catalytic processes that employ coenzyme recycling. Here, we investigate the efficiency of man-made synthetic biomimetics of the natural coenzymes NAD(P)H in redox biocatalysis. Extensive studies with a range of oxidoreductases belonging to the “ene” reductase family show that these biomimetics are excellent analogues of the natural coenzymes, revealed also in crystal structures of the ene reductase XenA with selected biomimetics. In selected cases, these biomimetics outperform the natural coenzymes. “Better-than-Nature” biomimetics should find widespread application in fine and specialty chemicals production by harnessing the power of high stereo-, regio-, and chemoselective redox biocatalysts and enabling reactions under mild conditions at low cost. PMID:26727612

An acyl-CoA synthetase in Mycobacterium tuberculosis involved in triacylglycerol accumulation during dormancy.

PubMed

Daniel, Jaiyanth; Sirakova, Tatiana; Kolattukudy, Pappachan

2014-01-01

Latent infection with dormant Mycobacterium tuberculosis is one of the major reasons behind the emergence of drug-resistant strains of the pathogen worldwide. In its dormant state, the pathogen accumulates lipid droplets containing triacylglycerol synthesized from fatty acids derived from host lipids. In this study, we show that Rv1206 (FACL6), which is annotated as an acyl-CoA synthetase and resembles eukaryotic fatty acid transport proteins, is able to stimulate fatty acid uptake in E. coli cells. We show that purified FACL6 displays acyl-coenzyme A synthetase activity with a preference towards oleic acid, which is one of the predominant fatty acids in host lipids. Our results indicate that the expression of FACL6 protein in Mycobacterium tuberculosis is significantly increased during in vitro dormancy. The facl6-deficient Mycobacterium tuberculosis mutant displayed a diminished ability to synthesize acyl-coenzyme A in cell-free extracts. Furthermore, during in vitro dormancy, the mutant synthesized lower levels of intracellular triacylglycerol from exogenous fatty acids. Complementation partially restored the lost function. Our results suggest that FACL6 modulates triacylglycerol accumulation as the pathogen enters dormancy by activating fatty acids.

Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis

PubMed Central

Mkrtchyan, Garik; Aleshin, Vasily; Parkhomenko, Yulia; Kaehne, Thilo; Luigi Di Salvo, Martino; Parroni, Alessia; Contestabile, Roberto; Vovk, Andrey; Bettendorff, Lucien; Bunik, Victoria

2015-01-01

Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism through the action of the coenzyme thiamin diphosphate (ThDP). However, positive effects, including improved cognition, of high thiamin doses in neurodegeneration may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here, we determine protein partners and metabolic pathways where thiamin acts beyond its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal kinase were identified as abundant proteins binding to thiamin- or thiazolium-modified sorbents. Kinetic studies, supported by structural analysis, revealed allosteric regulation of these proteins by thiamin and/or its derivatives. Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate shuttle may impact on malate/citrate exchange, responsible for exporting acetyl residues from mitochondria. Indeed, bioinformatic analyses found an association between thiamin- and thiazolium-binding proteins and the term acetylation. Our interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA production, but also an allosteric regulator of acetyl-CoA metabolism including regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover, thiamin action in neurodegeneration may also involve neurodegeneration-related 14-3-3, DJ-1 and β-amyloid precursor proteins identified among the thiamin- and/or thiazolium-binding proteins. PMID:26212886

Pyridine Nucleotide Complexes with Bacillus anthracis Coenzyme A-Disulfide Reductase: A Structural Analysis of Dual NAD(P)H Specificity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallen,J.; Paige, C.; Mallett, T.

2008-01-01

We have recently reported that CoASH is the major low-molecular weight thiol in Bacillus anthracis, and we have now characterized the kinetic and redox properties of the B. anthracis coenzyme A-disulfide reductase (CoADR, BACoADR) and determined the crystal structure at 2.30 Angstroms resolution. While the Staphylococcus aureus and Borrelia burgdorferi CoADRs exhibit strong preferences for NADPH and NADH, respectively, B. anthracis CoADR can use either pyridine nucleotide equally well. Sequence elements within the respective NAD(P)H-binding motifs correctly reflect the preferences for S. aureus and Bo. burgdorferi CoADRs, but leave questions as to how BACoADR can interact with both pyridine nucleotides.more » The structures of the NADH and NADPH complexes at ca. 2.3 Angstroms resolution reveal that a loop consisting of residues Glu180-Thr187 becomes ordered and changes conformation on NAD(P)H binding. NADH and NADPH interact with nearly identical conformations of this loop; the latter interaction, however, involves a novel binding mode in which the 2'-phosphate of NADPH points out toward solvent. In addition, the NAD(P)H-reduced BACoADR structures provide the first view of the reduced form (Cys42-SH/CoASH) of the Cys42-SSCoA redox center. The Cys42-SH side chain adopts a new conformation in which the conserved Tyr367'-OH and Tyr425'-OH interact with the nascent thiol(ate) on the flavin si-face. Kinetic data with Y367F, Y425F, and Y367, 425F BACoADR mutants indicate that Tyr425' is the primary proton donor in catalysis, with Tyr367' functioning as a cryptic alternate donor in the absence of Tyr425'.« less

Self-Incorporation of Coenzymes by Ribozymes

NASA Technical Reports Server (NTRS)

Breaker, Ronald R.; Joyce, Gerald F.

1995-01-01

RNA molecules that are assembled from the four standard nucleotides contain a limited number of chemical functional groups, a characteristic that is generally thought to restrict the potential for catalysis by ribozymes. Although polypeptides carry a wider range of functional groups, many contemporary protein-based enzymes employ coenzymes to augment their capabilities. The coenzymes possess additional chemical moieties that can participate directly in catalysis and thereby enhance catalytic function. In this work, we demonstrate a mechanism by which ribozymes can supplement their limited repertoire of functional groups through RNAcatalyzed incorporation of various coenzymes and coenzyme analogues. The group I ribozyme of Tetrahymena thermophila normally mediates a phosphoester transfer reaction that results in the covalent attachment of guanosine to the ribozyme. Here, a shortened version of the ribozyme is shown to catalyze the self-incorporation of coenzymes and coenzyme analogues, such as NAD+ and dephosphorylated CoA-SH. Similar ribozyme activities may have played an important role in the "RNA world," when RNA enzymes are thought to have maintained a complex metabolism in the absence of proteins and would have benefited from the inclusion of additional functional groups.

From Arylamine N-Acetyltransferase to Folate-Dependent Acetyl CoA Hydrolase: Impact of Folic Acid on the Activity of (HUMAN)NAT1 and Its Homologue (MOUSE)NAT2

PubMed Central

Laurieri, Nicola; Dairou, Julien; Egleton, James E.; Stanley, Lesley A.; Russell, Angela J.; Dupret, Jean-Marie; Sim, Edith; Rodrigues-Lima, Fernando

2014-01-01

Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2) can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH 3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH 3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme’s active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the developmental role of these enzymes and for improving chemotherapeutic approaches to pathological conditions including estrogen receptor-positive breast cancer. PMID:24823794

Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

PubMed

Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

2015-04-01

Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. © 2015 Royal Australasian College of Physicians.

Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

PubMed

Caso, Giuseppe; Kelly, Patricia; McNurlan, Margaret A; Lawson, William E

2007-05-15

Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. In contrast, no changes in pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

Coenzyme Q10 (PDQ®)—Health Professional Version

Cancer.gov

Coenzyme Q10 is a dietary supplement, and use of it as a treatment for cancer in humans has been investigated in only a limited manner. Get detailed information about Coenzyme Q10 use in cancer in this summary for clinicians.

A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency.

PubMed

Boitier, E; Degoul, F; Desguerre, I; Charpentier, C; François, D; Ponsot, G; Diry, M; Rustin, P; Marsac, C

1998-01-01

We report severe coenzyme Q10 deficiency of muscle in a 4-year-old boy presenting with progressive muscle weakness, seizures, cerebellar syndrome, and a raised cerebro-spinal fluid lactate concentration. State-3 respiratory rates of muscle mitochondria with glutamate, pyruvate, palmitoylcarnitine, and succinate as respiratory substrates were markedly reduced, whereas ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine were oxidized normally. The activities of complexes I, II, III and IV of the electron transport chain were normal, but the activities of complexes I+III and II+III, both systems requiring coenzyme Q10 as an electron carrier, were dramatically decreased. These results suggested a defect in the mitochondrial coenzyme Q10 content. This was confirmed by the direct assessment of coenzyme Q10 level by high-performance liquid chromatography in patient's muscle homogenate and isolated mitochondria, revealing levels of 16% and 6% of the control values, respectively. We did not find any impairment of the respiratory chain either in a lymphoblastoid cell line or in skin cultured fibroblasts from the patient, suggesting that the coenzyme Q10 depletion was tissue-specific. This is a new case of a muscle deficiency of mitochondrial coenzyme Q in a patient suffering from an encephalomyopathy.

[Effect of procaine and procaine metabolites on coenzyme A and acetyl coenzyme A concentration in various tissues of the rat].

PubMed

Kietzmann, M; Kaemmerer, K

1989-01-01

In rats treated with procaine hydrochloride, diethylaminoethanol, monoethylaminoethanol, ethanolamine, as well as a combination of procaine hydrochloride and haematoporphyrine the ratio of acetyl coenzyme A and coenzyme A clearly was enhanced in the liver and to a minor extent in the cerebellum. In the tissue of cerebral cortex, heart, muscle and duodenum no corresponding effects were demonstrated. These findings, showing a further intermediary effect of orally administered procaine, can be interpreted as an influence in intermediary energy utilisation.

[The isozymes of stearil-coenzymeA-desaturase and insulin activity in the light of phylogenetic theory of pathology. Oleic fatty acid and realization of biologic functions of trophology and locomotion].

PubMed

2013-11-01

The formation of function of isozymes of stearil-coenzymeA-desaturases occured at the different stages of phylogeny under realization of biologic function of trophology (stearil-coenzymeA-desaturase 1) and biologic function of locomotion, insulin system (stearil-coenzymeA-desaturase 2) billions years later. The stearil-coenzymeA-desaturase 1 transforms in C 18:1 oleic fatty acid only exogenous C 16:0 palmitinic saturated fatty acid. The stearil-coenzymeA-desaturase 2 transforms only endogenic palmitinic saturated fatty acid, synthesized form glucose. The biologic role of insulin is in energy support of biologic function of locomotion. Insulin through expressing stearil-coenzymeA-desaturase 2 transforms energetically non-optimal palmitinic variation of metabolism of substrates into highly effective oleic variation for cells' groundwork of energy (saturated fatty acid and mono fatty acid). The surplus of palmitinic saturated fatty acid in food is enabled in pathogenesis of resistance to insulin and derangement of synthesis of hormone by beta-cells of islets. The resistance to insulin and diabetes mellitus are primarily the derangement of metabolism of saturated fatty acids with mono fatty acids, energy problems of organism and only afterwards the derangement of metabolism of carbohydrates. It is desirable to restrict food intake of exogenous palmitinic saturated fatty acid. The reasons are low expression of independent of insulin stearil-coenzymeA-desaturase 2, marked lipotoxicity of polar form of palmitinic saturated fatty acid and synthesis of non-optimal palmitinic triglycerides instead of physiologic and more energetically more effective oleic triglycerides.

Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

PubMed

Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

2009-02-27

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

Pantoic acid can by synthesized in good prebiotic yield from isobutyraldehyde or alpha-ketoisovaleric acid + H2CO + HCN. Isobutyraldehyde is the Strecker precursor to valine and alpha-ketoisovaleric acid is the valine transamination product. Mg2+ and Ca2+ as well as several transition metals are catalysts for the alpha-ketoisovaleric acid reaction. Pantothenic acid is produced from pantoyl lactone (easily formed from pantoic acid) and the relatively high concentrations of beta-alanine that would be formed on drying prebiotic amino acid mixtures. There is no selectivity for this reaction over glycine, alanine, or gamma-amino butyric acid. The components of coenzyme A are discussed in terms of ease of prebiotic formation and stability and are shown to be plausible choices, but many other compounds are possible. The gamma-OH of pantoic acid needs to be capped to prevent decomposition of pantothenic acid. These results suggest that coenzyme A function was important in the earliest metabolic pathways and that the coenzyme A precursor contained most of the components of the present coenzyme.

LC/MS/MS analysis of α-tocopherol and coenzyme Q10 content in lyophilized royal jelly, beebread and drone homogenate.

PubMed

Hryniewicka, Marta; Karpinska, Agnieszka; Kijewska, Marta; Turkowicz, Monika Joanna; Karpinska, Joanna

2016-11-01

This study shows the results of application liquid chromatography-tandem mass spectrometry (LC/MS/MS) for assay of the content of α-tocopherol and coenzyme Q 10 in bee products of animal origin, i.e. royal jelly, beebread and drone homogenate. The biological matrix was removed using extraction with n-hexane. It was found that drone homogenate is a rich source of coenzyme Q 10 . It contains only 8 ± 1 µg/g of α-tocopherol and 20 ± 2 µg/g of coenzyme Q 10 . The contents of assayed compounds in royal jelly were 16 ± 3 and 8 ± 0.2 µg/g of α-tocopherol and coenzyme Q 10 , respectively. Beebread appeared to be the richest of α-tocopherol. Its level was 80 ± 30 µg/g, while the level of coenzyme Q 10 was only 11.5 ± 0.3 µg/g. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins.

PubMed

Chapidze, G; Kapanadze, S; Dolidze, N; Bachutashvili, Z; Latsabidze, N

2005-01-01

The goal of the present research was to assess the efficacy of combination treatment with antioxidant coenzyme Q10 and simvastatin as well as coenzyme Q10 without statin therapy in order to prevent coronary atherosclerosis. 42 outpatients were divided into 2 groups: receiving coenzyme Q10 (Hasco-Lek, Poland) 60mg daily and its combination with simvastatin (zocor, vasilip) 10mg daily for an 8-week period. The treatment with coenzyme Q10 demonstrated its potential independent role in positive modification of oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio, platelet aggregability. Taking into consideration the obtained results the study supports the use of coenzyme Q10 in combination with statins. Suggested attractive approach may result in complete correction of dislipidemia, reverse of endothelial dysfunction, reduce degree of oxidative stress and platelet aggregability. Consequently such a combination may be beneficial in preventing of further development of atherosclerosis in native coronary arteries as well as in bypass grafts in all coronary heart disease patients with or without myocardial revascularization.

Prebiotic syntheses of vitamin coenzymes: I. Cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M)

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

The reaction of NH3 and SO3(2-) with ethylene sulfide is shown to be a prebiotic synthesis of cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M). A similar reaction with ethylene imine would give cysteamine and taurine. Ethylene oxide would react with NH3 and N(CH3)3 to give the phospholipid components ethanolamine and choline. The prebiotic sources of ethylene sulfide, ethylene imine and ethylene oxide are discussed. Cysteamine itself is not a suitable thioester for metabolic processes because of acyl transfer to the amino group, but this can be prevented by using an amide of cysteamine. The use of cysteamine in coenzyme A may have been due to its prebiotic abundance. The facile prebiotic synthesis of both cysteamine and coenzyme M suggests that they were involved in very early metabolic pathways.

High degree of efficacy in the treatment of cyclic vomiting syndrome with combined co-enzyme Q10, L-carnitine and amitriptyline, a case series

PubMed Central

2011-01-01

Background Cyclic vomiting syndrome (CVS), defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling and historically difficult-to-treat condition associated with migraine headache and mitochondrial dysfunction. Limited data suggests that the anti-migraine therapies amitriptyline and cyproheptadine, and the mitochondrial-targeted cofactors co-enzyme Q10 and L-carnitine, have efficacy in episode prophylaxis. Methods A retrospective chart review of 42 patients seen by one clinician that met established CVS diagnostic criteria revealed 30 cases with available outcome data. Participants were treated on a loose protocol consisting of fasting avoidance, co-enzyme Q10 and L-carnitine, with the addition of amitriptyline (or cyproheptadine in those < 5 years) in refractory cases. Blood level monitoring of the therapeutic agents featured prominently in management. Results Vomiting episodes resolved in 23 cases, and improved by > 75% and > 50% in three and one additional case respectively. Among the three treatment failures, two could not tolerate amitriptyline (as was also the case in the child with only > 50% efficacy) and one had multiple congenital gastrointestinal anomalies. Excluding the latter case, substantial efficacy (> 75% response) was 26/29 at the start of treatment, and 26/26 in those able to tolerate the regiment, including high dosages of amitriptyline. Conclusion Our data suggest that a protocol consisting of mitochondrial-targeted cofactors (co-enzyme Q10 and L-carnitine) plus amitriptyline (or possibly cyproheptadine in preschoolers) coupled with blood level monitoring is highly effective in the prevention of vomiting episodes. PMID:21846334

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study.

PubMed

Tuncer, Ahmet Ali; Bozkurt, Mehmet Fatih; Koken, Tulay; Dogan, Nurhan; Pektaş, Mine Kanat; Baskin Embleton, Didem

2016-01-01

Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

PubMed

Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

PubMed

Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

1993-01-01

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.

Elucidation of the biosynthesis of the methane catalyst coenzyme F430

PubMed Central

Moore, Simon J.; Sowa, Sven T.; Schuchardt, Christopher; Deery, Evelyne; Lawrence, Andrew D.; Ramos, José Vazquez; Billig, Susan; Birkemeyer, Claudia; Chivers, Peter T.; Howard, Mark J.; Rigby, Stephen E. J.; Layer, Gunhild; Warren, Martin J.

2017-01-01

Summary Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilisation of methane through anaerobic methane oxidation. The enzyme employs an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a novel methyl radical/Ni(II)-thiolate intermediate. However, the biosynthesis of coenzyme F430 from the common primogenitor uroporphyrinoge III, incorporating 11 steric centres into the macrocycle, has remained poorly understood although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamisation and carbocyclic ring formation. We have now identified the proteins that catalyse coenzyme F430 biosynthesis from sirohydrochlorin, termed CfbA-E, and shown their activity. The research completes our understanding of how nature is able to construct its repertoire of tetrapyrrole-based life pigments, permitting the development of recombinant systems to utilise these metalloprosthetic groups more widely. PMID:28225763

[Effect of phlebodium decumanum and coenzyme Q10 on sports performance in professional volleyball players].

PubMed

García Verazaluce, Juan José; Vargas Corzo, María Del Carmen; Aguilar Cordero, María José; Ocaña Peinado, Francisco; Sarmiento Ramírez, Álvaro; Guisado Barrilao, Rafael

2014-10-03

Physical training programmes are based on provoking transitory states of fatigue in order to induce super compensation by the biological systems involved in the activity, in order to improve the athlete's medium-long term performance. The administration of nutritional supplements with antioxidant and immunomodulatory properties, such as Phlebodium decumanum and coenzyme Q10, can be a very advantageous means of achieving recovery from the inflammation and tissue damage caused by the stress of prolonged, intense exercise. An experimental, longitudinal, double- blind experiment was conducted, with three randomised groups obtained from a sample of 30 male volleyball players (aged 22-32 years) at the University of Granada, with a high level of training (17 hours a week during the 6 months preceding the study). The effects were then evaluated of a month-long physical training programme, common to all the study groups, associated with the simultaneous administration of the following nutritional supplements: Phlebodium decumanum (4 capsules of 400 mg/capsule, daily), Experimental Group 1; Phlebodium decumanum (same dose and schedule as Group 1) plus coenzyme Q10 (4 capsules of 30 mg/ capsule, daily), Experimental Group 2; a placebo substance, Control Group. The following dependent blood variables were examined to assess the effects of the intervention on the basal immune and endocrine-metabolic profile: cortisol and interleukin-6, both related to the axis of exercise-induced stress; and lactic acid and ammonium, related essentially to the anaerobic metabolism of energy. All the study groups presented favourable adaptive changes with respect to the endocrine-metabolic and immune profile, as reflected by a significant decrease in the post-test concentrations of cortisol, interleukin 6, lactic acid and ammonium, compared to the values recorded before the physical activity with/without nutritional supplement, per protocol. The groups that achieved the most favourable profile were those which had received nutritional supplementation, rather than the placebo, and among the former, those which had received the double- strength supplement with Phlebodium decumanum plus coenzyme Q10. The intake of Phlebodium decumanum plus coenzyme Q10 for 4 weeks produced protective effects on the endocrine-metabolic and immune profile, which we attribute to the immunomodulatory and antioxidant properties of these substances, which are highly beneficial not only in terms of delaying fatigue and improving athletic performance, but also in reducing the risk of injuries associated with high intensity exercise. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Cloning, Baeyer-Villiger Biooxidations, and Structures of the Camphor Pathway 2-Oxo-Δ3-4,5,5-Trimethylcyclopentenylacetyl-Coenzyme A Monooxygenase of Pseudomonas putida ATCC 17453

PubMed Central

Leisch, Hannes; Shi, Rong; Grosse, Stephan; Morley, Krista; Bergeron, Hélène; Cygler, Miroslaw; Iwaki, Hiroaki; Hasegawa, Yoshie

2012-01-01

A dimeric Baeyer-Villiger monooxygenase (BVMO) catalyzing the lactonization of 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A (CoA), a key intermediate in the metabolism of camphor by Pseudomonas putida ATCC 17453, had been initially characterized in 1983 by Ougham and coworkers (H. J. Ougham, D. G. Taylor, and P. W. Trudgill, J. Bacteriol. 153:140–152, 1983). Here we cloned and overexpressed the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase (OTEMO) in Escherichia coli and determined its three-dimensional structure with bound flavin adenine dinucleotide (FAD) at a 1.95-Å resolution as well as with bound FAD and NADP+ at a 2.0-Å resolution. OTEMO represents the first homodimeric type 1 BVMO structure bound to FAD/NADP+. A comparison of several crystal forms of OTEMO bound to FAD and NADP+ revealed a conformational plasticity of several loop regions, some of which have been implicated in contributing to the substrate specificity profile of structurally related BVMOs. Substrate specificity studies confirmed that the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetic acid coenzyme A ester is preferred over the free acid. However, the catalytic efficiency (kcat/Km) favors 2-n-hexyl cyclopentanone (4.3 × 105 M−1 s−1) as a substrate, although its affinity (Km = 32 μM) was lower than that of the CoA-activated substrate (Km = 18 μM). In whole-cell biotransformation experiments, OTEMO showed a unique enantiocomplementarity to the action of the prototypical cyclohexanone monooxygenase (CHMO) and appeared to be particularly useful for the oxidation of 4-substituted cyclohexanones. Overall, this work extends our understanding of the molecular structure and mechanistic complexity of the type 1 family of BVMOs and expands the catalytic repertoire of one of its original members. PMID:22267661

Coenzyme Q10 (PDQ®)—Patient Version

Cancer.gov

Coenzyme Q10 is naturally made by the body and can be taken as a pill or injection. Studies have shown it to help protect the heart from damaging side effects of doxorubicin and to stimulate the immune system in cancer patients. Read about the results of clinical trials in cancer patients using coenzyme Q10 in this expert-reviewed summary.

Production of a Brassica napus low-molecular mass acyl-coenzyme A-binding protein in Arabidopsis alters the acyl-coenzyme A pool and acyl composition of oil in seeds

USDA-ARS?s Scientific Manuscript database

Low-molecular mass (10 kD) cytosolic acyl-coenzyme A-binding protein (ACBP) has a substantial influence over fatty acid (FA) composition in oilseeds, possibly via an effect on the partitioning of acyl groups between elongation and desaturation pathways. Previously, we demonstrated that the expressio...

Coenzyme Q10 for heart failure.

PubMed

Madmani, Mohammed E; Yusuf Solaiman, Ahmad; Tamr Agha, Khalil; Madmani, Yasser; Shahrour, Yasser; Essali, Adib; Kadro, Waleed

2014-06-02

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted. To review the safety and efficacy of coenzyme Q10 in heart failure. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase. Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers. We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution. No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.

The Effect of Coenzyme Q10 Supplementation on Circulating Levels of Novel Adipokine Adipolin/CTRP12 in Overweight and Obese Patients with Type 2 Diabetes.

PubMed

Mehrdadi, P; Kolahdouz Mohammadi, R; Alipoor, E; Eshraghian, M R; Esteghamati, A; Hosseinzadeh-Attar, M J

2017-03-01

Background: Adipolin, the novel adipokine that is proposed to be reduced in diabetes, obesity and inflammation, may improve glycemic control. It is known that coenzyme Q10 could improve insulin sensitivity. The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients. Material & Methods: Sixty four patients with type 2 diabetes and 25

The chaperone role of the pyridoxal 5'-phosphate and its implications for rare diseases involving B6-dependent enzymes.

PubMed

Cellini, Barbara; Montioli, Riccardo; Oppici, Elisa; Astegno, Alessandra; Voltattorni, Carla Borri

2014-02-01

The biologically active form of the B6 vitamers is pyridoxal 5'-phosphate (PLP), which plays a coenzymatic role in several distinct enzymatic activities ranging from the synthesis, interconversion and degradation of amino acids to the replenishment of one-carbon units, synthesis and degradation of biogenic amines, synthesis of tetrapyrrolic compounds and metabolism of amino-sugars. In the catalytic process of PLP-dependent enzymes, the substrate amino acid forms a Schiff base with PLP and the electrophilicity of the PLP pyridine ring plays important roles in the subsequent catalytic steps. While the essential role of PLP in the acquisition of biological activity of many proteins is long recognized, the finding that some PLP-enzymes require the coenzyme for refolding in vitro points to an additional role of PLP as a chaperone in the folding process. Mutations in the genes encoding PLP-enzymes are causative of several rare inherited diseases. Patients affected by some of these diseases (AADC deficiency, cystathionuria, homocystinuria, gyrate atrophy, primary hyperoxaluria type 1, xanthurenic aciduria, X-linked sideroblastic anaemia) can benefit, although at different degrees, from the administration of pyridoxine, a PLP precursor. The effect of the coenzyme is not limited to mutations that affect the enzyme-coenzyme interaction, but also to those that cause folding defects, reinforcing the idea that PLP could play a chaperone role and improve the folding efficiency of misfolded variants. In this review, recent biochemical and cell biology studies highlighting the chaperoning activity of the coenzyme on folding-defective variants of PLP-enzymes associated with rare diseases are presented and discussed. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Inborn errors of ketogenesis and ketone body utilization.

PubMed

Sass, Jörn Oliver

2012-01-01

Ketone bodies acetoacetate and 3-hydroxy-n-butyric acid are metabolites derived from fatty acids and ketogenic amino acids such as leucine. They are mainly produced in the liver via reactions catalyzed by the ketogenic enzymes mitochondrial 3-hydroxy-3-methylglutary-coenzyme A synthase and 3-hydroxy-3-methylglutary-coenzyme A lyase. After prolonged starvation, ketone bodies can provide up to two-thirds of the brain's energy requirements. The rate-limiting enzyme of ketone body utilization (ketolysis) is succinyl-coenzyme A:3-oxoacid coenzyme A transferase. The subsequent step of ketolysis is catalyzed by 2-methylactoacetyl-coenzyme A thiolase, which is also involved in isoleucine catabolism. Inborn errors of metabolism affecting those four enzymes are presented and discussed in the context of differential diagnoses. While disorders of ketogenesis can present with hypoketotic hypoglycemia, inborn errors of ketolysis are characterized by metabolic decompensations with ketoacidosis. If those diseases are considered early and appropriate treatment is initiated without delay, patients with inborn errors of ketone body metabolism often have a good clinical outcome.

Redox Specificity of 2-Hydroxyacid-Coupled NAD+/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics

PubMed Central

Durani, Susheel

2013-01-01

With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD+-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD+ (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. PMID:24391777

NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells.

PubMed

Takahashi, Takayuki; Okuno, Masaaki; Okamoto, Tadashi; Kishi, Takeo

2008-01-01

We purified an NADPH-dependent coenzyme Q reductase (NADPH-CoQ reductase) in rat liver cytosol and compared its enzymatic properties with those of the other CoQ10 reductases such as NADPH: quinone acceptor oxidoreductase 1 (NQO1), lipoamide dehydrogenase, thioredoxine reductase and glutathione reductase. NADPH-CoQ reductase was the only enzyme that preferred NADPH to NADH as an electron donor and was also different from the other CoQ10 reductases in the sensitivities to its inhibitors and stimulators. Especially, Zn2+ was the most powerful inhibitor for NADPH-CoQ reductase, but CoQ10 reduction by the other CoQ10 reductases could not be inhibited by Zn2+. Furthermore, the reduction of the CoQ9 incorporated into HeLa cells was also inhibited by Zn2+ in the presence of pyrithione, a zinc ionophore. Moreover, NQO1 gene silencing in HeLa cells by transfection of a small interfering RNA resulted in lowering of both the NQO1 protein level and the NQO1 activity by about 75%. However, this transfection did not affect the NADPH-CoQ reductase activity and the reduction of CoQ9 incorporated into the cells. These results suggest that the NADPH-CoQ reductase located in cytosol may be the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells.

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

PubMed

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis.

PubMed

Peel, Margaret M; Cooke, Marie; Lewis-Peel, Helen J; Lea, Rodney A; Moyle, Wendy

2015-12-01

To determine if coenzyme Q(10) alleviates fatigue in the late-onset sequelae of poliomyelitis. Parallel-group, randomized, placebo-controlled trial. Coenzyme Q(10) has been shown to boost muscle energy metabolism in post-polio subjects but it does not promote muscle strength, endurance or function in polio survivors with post-poliomyelitis syndrome. However, the collective increased energy metabolism might contribute to a reduction in post-polio fatigue. Polio survivors from the Australian post-polio networks in Queensland and New South Wales who attribute a moderate to high level of fatigue to their diagnosed late-onset sequelae of poliomyelitis. Those with fatigue-associated comorbidities of diabetes, anaemia, hypothyroidism and fibromyalgia were excluded. Participants were assigned (1:1), with stratification of those who use energy-saving mobility aids, to receive 100 mg coenzyme Q(10) or matching placebo daily for 60 days. Participants and investigators were blinded to group allocation. Fatigue was assessed by the Multidimensional Assessment of Fatigue as the primary outcome and the Fatigue Severity Scale as secondary outcome. Of 103 participants, 54 were assigned to receive coenzyme Q(10) and 49 to receive the placebo. The difference in the mean score reductions between the two groups was not statistically significant for either fatigue measure. Oral supplementation with coenzyme Q(10) was safe and well-tolerated. A daily dose of 100 mg coenzyme Q(10) for 60 days does not alleviate the fatigue of the late-onset sequelae of poliomyelitis. The registration number for the clinical trial is ACTRN 12612000552886. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microtubular conductometric biosensor for ethanol detection.

PubMed

Ajay, A K; Srivastava, Divesh N

2007-09-30

A conductometric sensor using microtubules of polyaniline as transducer cum immobilization matrix is reported, capable of detecting ethanol in liquid phase. Enzyme ADH (alcohol dehydrogenase) and its coenzyme NAD+ have been used to improve the selectivity of the sensor. The sensor concept is based on the protonation of the polyaniline by the hydrogen ion produced in the enzyme-catalyzed reaction, leading to changes in the electrical conductance of the polyaniline. The sensor works well on the physiological pH, can detect ethanol as low as 0.02% (v/v) (0.092 M) and has a linear trend at par healthcare guidelines. The sensor responses were measured in various permutation and combination of enzyme and coenzyme concentrations and site of immobilization. The sensor shows minor interference with other functional groups and alcohols. The possible causes for such interference have been discussed.

Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem.

PubMed

Zozina, Vladlena I; Covantev, Serghei; Goroshko, Olga A; Krasnykh, Liudmila M; Kukes, Vladimir G

2018-04-15

The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses.

PubMed

Arany, Istvan; Carter, Anthony; Hall, Samuel; Fulop, Tibor; Dixit, Mehul

2017-02-01

Chronic nicotine exposure (via smoking, E-cigarettes) increases oxidative stress in the kidney that sensitizes it to additional injury in experimental models and in the renal patient. The pro-apoptotic p66 shc protein-via serine36 phosphorylation that facilitates its mitochondrial translocation and therein cytochrome c binding-generates oxidative stress that leads to injury of renal proximal tubule cells during chronic nicotine exposure. Coenzyme Q10-a clinically safe antioxidant-has been used against nicotine/smoke extract-associated oxidative stress in various non-renal cells. This study explored the anti-oxidant/anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E). We studied the anti-oxidant effect of 10 µM Coenzyme Q10 using various mutants of the p66shc gene and also determined the induction of selected anti-oxidant entities (antioxidant response element, promoter of the manganese superoxide dismutase gene) in reporter luciferase assay during oxidative stress induced by 200 µM nicotine. Our studies revealed that Coenzyme Q10 strongly inhibits nicotine-mediated production of reactive oxygen species and consequent apoptosis that requires serine36 phosphorylation but not mitochondrial translocation/cytochrome c binding of p66 shc . While both nicotine and Coenzyme Q10 stimulates the p66shc promoter, only nicotine exposure results in mitochondrial translocation of p66 shc . In contrast, the Coenzyme Q10-stimulated and non-mitochondrial p66 shc activates the anti-oxidant manganese superoxide dismutase promoter via the antioxidant response elements and hence, rescues cells from nicotine-induced oxidative stress and consequent apoptosis.

Neutron study of B 12 coenzyme at 15 K

NASA Astrophysics Data System (ADS)

Bouquiere, J. P.

1992-06-01

This high resolution and low temperature study, at 15 K, of the vitamin B 12 coenzyme ( C72H100N18O17PCo) was undertaken to confirm and clarify the water networks identified at 279 K by Savage [1]. Details of the data collection and refinement of the low temperature structure are described, a comparison of the coenzyme molecule structures at 15 and 279 K is made, and that of solvent structures outlined.

Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis.

PubMed

Evans, Joanna C; Trujillo, Carolina; Wang, Zhe; Eoh, Hyungjin; Ehrt, Sabine; Schnappinger, Dirk; Boshoff, Helena I M; Rhee, Kyu Y; Barry, Clifton E; Mizrahi, Valerie

2016-12-09

Mycobacterium tuberculosis relies on its own ability to biosynthesize coenzyme A to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the essential pantothenate and coenzyme A biosynthesis pathways have attracted attention as targets for tuberculosis drug development. To identify the optimal step for coenzyme A pathway disruption in M. tuberculosis, we constructed and characterized a panel of conditional knockdown mutants in coenzyme A pathway genes. Here, we report that silencing of coaBC was bactericidal in vitro, whereas silencing of panB, panC, or coaE was bacteriostatic over the same time course. Silencing of coaBC was likewise bactericidal in vivo, whether initiated at infection or during either the acute or chronic stages of infection, confirming that CoaBC is required for M. tuberculosis to grow and persist in mice and arguing against significant CoaBC bypass via transport and assimilation of host-derived pantetheine in this animal model. These results provide convincing genetic validation of CoaBC as a new bactericidal drug target.

In vitro methanol production from methyl coenzyme M using the Methanosarcina barkeri MtaABC protein complex.

PubMed

Dong, Ming; Gonzalez, Tara D; Klems, Meghan M; Steinberg, Lisa M; Chen, Wilfred; Papoutsakis, Eleftherios T; Bahnson, Brian J

2017-09-01

Methanol:coenzyme M methyltransferase is an enzyme complex composed of three subunits, MtaA, MtaB, and MtaC, found in methanogenic archaea and is needed for their growth on methanol ultimately producing methane. MtaABC catalyzes the energetically favorable methyl transfer from methanol to coenzyme M to form methyl coenzyme M. Here we demonstrate that this important reaction for possible production of methanol from the anaerobic oxidation of methane can be reversed in vitro. To this effect, we have expressed and purified the Methanosarcina barkeri MtaABC enzyme, and developed an in vitro functional assay that demonstrates MtaABC can catalyze the energetically unfavorable (ΔG° = 27 kJ/mol) reverse reaction starting from methyl coenzyme M and generating methanol as a product. Demonstration of an in vitro ability of MtaABC to produce methanol may ultimately enable the anaerobic oxidation of methane to produce methanol and from methanol alternative fuel or fuel-precursor molecules. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1243-1249, 2017. © 2017 American Institute of Chemical Engineers.

Effects of various vitamins and coenzymes Q on reactions involving alpha-hydroxyl-containing radicals.

PubMed

Shadyro, Oleg I; Sosnovskaya, Anna A; Edimecheva, Irina P; Grintsevich, Ivan B; Lagutin, Petr Yu; Alekseev, Aleksei V; Kazem, Kamel

2005-07-01

Effects of vitamins B, C, E, K and P, as well as coenzymes Q, on formation of final products of radiation-induced free-radical transformations of ethanol, ethylene glycol, alpha-methylglycoside and glucose in aqueous solutions were studied. Based on the obtained results, it can be concluded that there are substances among vitamins and coenzymes that effectively interact with alpha-hydroxyl-containing radicals. In the presence of these substances, recombination reactions of alpha-hydroxyalkyl radicals and fragmentation of alpha-hydroxy-beta-substituted organic radicals are suppressed. It has been established that the observed effects are due to the ability of the vitamins and coenzymes under study to either oxidize alpha-hydroxyl-containing radicals yielding the respective carbonyl compounds or reduce them into the initial molecules.

Hepatic Concentration and Distribution of Coenzyme A and Carnitine during a Streptococcus pneumoniae Infection in the Rat: Possible Implications on Fatty Acid Metabolism and Ketogenesis

DTIC Science & Technology

1981-01-09

subcellular distribution of carnitine and coenzyme A (CoA). Compared to fasted control ILJ rats, fasted-infected rats have a decreased ketogenic capacity...decreased ketogenic capacity that is associated with an accumulation of total hepatic carnitine and a decrease in total hepatic coenzyme A. The...cholesterol. IiA .Ii INTRODUCTION Rats infected with Streptococcus pneumoniae have a decreased hep-tic ketogenic capacity which is associated with an

Thermodynamics of various F420 coenzyme models as sources of electrons, hydride ions, hydrogen atoms and protons in acetonitrile.

PubMed

Xia, Ke; Shen, Guang-Bin; Zhu, Xiao-Qing

2015-06-14

32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3 and N10) in the core structure (XFH(-)) were designed and synthesized and the thermodynamic driving forces (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the 32 XFH(-) releasing hydride ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32 XFH˙ releasing protons and hydrogen atoms and the thermodynamic driving forces of XF(-)˙ releasing electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The effects of the methyl group at N1, N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were examined; the results show that seating arrangements of the methyl group and the negative charge have remarkably different effects on the thermodynamic properties of the F420 coenzyme models and their related reaction intermediates. The effects of the substituents at C7 and C8 on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were also examined; the results show that the substituents at C7 and C8 have good Hammett linear free energy relationships with the six thermodynamic parameters. Meanwhile, a reasonable determination of possible reactions between members of the F420 family and NADH family in vivo was given according to a thermodynamic analysis platform constructed using the elementary step thermodynamic parameter of F420 coenzyme model 2FH(-) and NADH model MNAH releasing hydride ions in acetonitrile. The information disclosed in this work can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as a class of very important organic sources of electrons, hydride ions, hydrogen atoms and protons, but also strongly promote the fast development of the chemistry and applications of F420 coenzyme.

Medical treatment with thiamine, coenzyme Q, vitamins E and C, and carnitine improved obstructive sleep apnea in an adult case of Leigh disease.

PubMed

Mermigkis, Charalampos; Bouloukaki, Izolde; Mastorodemos, Vasileios; Plaitakis, Andreas; Alogdianakis, Vangelis; Siafakas, Nikolaos; Schiza, Sophia

2013-12-01

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

Accelerated methanogenesis from aliphatic and aromatic hydrocarbons under iron- and sulfate-reducing conditions.

PubMed

Siegert, Michael; Cichocka, Danuta; Herrmann, Steffi; Gründger, Friederike; Feisthauer, Stefan; Richnow, Hans-Hermann; Springael, Dirk; Krüger, Martin

2011-02-01

The impact of four electron acceptors on hydrocarbon-induced methanogenesis was studied. Methanogenesis from residual hydrocarbons may enhance the exploitation of oil reservoirs and may improve bioremediation. The conditions to drive the rate-limiting first hydrocarbon-oxidizing steps for the conversion of hydrocarbons into methanogenic substrates are crucial. Thus, the electron acceptors ferrihydrite, manganese dioxide, nitrate or sulfate were added to sediment microcosms acquired from two brackish water locations. Hexadecane, ethylbenzene or 1-(13)C-naphthalene were used as model hydrocarbons. Methane was released most rapidly from incubations amended with ferrihydrite and hexadecane. Ferrihydrite enhanced only hexadecane-dependent methanogenesis. The rates of methanogenesis were negatively affected by sulfate and nitrate at concentrations of more than 5 and 1 mM, respectively. Metal-reducing Geobacteraceae and potential sulfate reducers as well as Methanosarcina were present in situ and in vitro. Ferrihydrite addition triggered the growth of Methanosarcina-related methanogens. Additionally, methane was removed concomitantly by anaerobic methanotrophy. ANME-1 and -2 methyl coenzyme M reductase genes were detected, indicating anaerobic methanotrophy as an accompanying process [Correction added 16 December after online publication: 'methyl coenzyme A' changed to 'methyl coenzyme M' in this sentence]. The experiments presented here demonstrate the feasibility of enhancing methanogenic alkane degradation by ferrihydrite or sulfate addition in different geological settings. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Coenzymes, Viruses and the RNA World

NASA Astrophysics Data System (ADS)

Reyes-Prieto, F.; Hernández-Morales, R.; Jácome, R.; Becerra, A.; Lazcano, A.

2017-07-01

Bioinformatic search for homologous sequences involved in ribonucleotidyl-coenzyme biosynthesis has shown that they are absent in RNA viral genomes, indicating that RNA viruses may not be direct holdovers from an ancient RNA/protein world.

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A.

PubMed

Keefe, A D; Newton, G L; Miller, S L

1995-02-23

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

NASA Technical Reports Server (NTRS)

Keefe, A. D.; Newton, G. L.; Miller, S. L.

1995-01-01

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

Structural and Biochemical Characterization of Cinnamoyl-CoA Reductases1

PubMed Central

Walker, Alexander M.

2017-01-01

Cinnamoyl-coenzyme A reductase (CCR) catalyzes the reduction of hydroxycinnamoyl-coenzyme A (CoA) esters using NADPH to produce hydroxycinnamyl aldehyde precursors in lignin synthesis. The catalytic mechanism and substrate specificity of cinnamoyl-CoA reductases from sorghum (Sorghum bicolor), a strategic plant for bioenergy production, were deduced from crystal structures, site-directed mutagenesis, and kinetic and thermodynamic analyses. Although SbCCR1 displayed higher affinity for caffeoyl-CoA or p-coumaroyl-CoA than for feruloyl-CoA, the enzyme showed significantly higher activity for the latter substrate. Through molecular docking and comparisons between the crystal structures of the Vitis vinifera dihydroflavonol reductase and SbCCR1, residues threonine-154 and tyrosine-310 were pinpointed as being involved in binding CoA-conjugated phenylpropanoids. Threonine-154 of SbCCR1 and other CCRs likely confers strong substrate specificity for feruloyl-CoA over other cinnamoyl-CoA thioesters, and the T154Y mutation in SbCCR1 led to broader substrate specificity and faster turnover. Through data mining using our structural and biochemical information, four additional putative CCR genes were discovered from sorghum genomic data. One of these, SbCCR2, displayed greater activity toward p-coumaroyl-CoA than did SbCCR1, which could imply a role in the synthesis of defense-related lignin. Taken together, these findings provide knowledge about critical residues and substrate preference among CCRs and provide, to our knowledge, the first three-dimensional structure information for a CCR from a monocot species. PMID:27956488

Heterologous Expression of Bacterial Epoxyalkane:Coenzyme M Transferase and Inducible Coenzyme M Biosynthesis in Xanthobacter Strain Py2 and Rhodococcus rhodochrous B276

PubMed Central

Krum, Jonathan G.; Ensign, Scott A.

2000-01-01

Coenzyme M (CoM) (2-mercaptoethanesulfonic acid) biosynthesis is shown to be coordinately regulated with the expression of the enzymes of alkene and epoxide metabolism in the propylene-oxidizing bacteria Xanthobacter strain Py2 and Rhodococcus rhodochrous strain B276. These results provide the first evidence for the involvement of CoM in propylene metabolism by R. rhodochrous and demonstrate for the first time the inducible nature of eubacterial CoM biosynthesis. PMID:10762269

Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism.

PubMed

Al-Ghamdi, Mashael; Al-Ayadhi, Laila; El-Ansary, Afaf

2014-02-25

Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters. In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in biochemical markers and DNA double strand breaks.

Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism

PubMed Central

2014-01-01

Background Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. Results The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA–treated rats demonstrated in a remarkable amelioration of most of the measured parameters. Conclusion In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in biochemical markers and DNA double strand breaks. PMID:24568717

Antisense down-regulation of 4CL expression alters lignification, tree growth, and saccharification potential of field-grown poplar

Treesearch

Steven L. Voelker; Barbara Lachenbruch; Frederick C. Meinzer; Michael Jourdes; Chanyoung Ki; Ann M. Patten; Laurence B. Davin; Norman G. Lewis; Gerald A. Tuskan; Lee Gunter; Stephen R. Decker; Michael J. Selig; Robert Sykes; Michael E. Himmel; Peter Kitin; Olga Shevchenko; Steven H. Strauss

2010-01-01

Transgenic down-regulation of the Pt4CL1 gene family encoding 4-coumarate:coenzyme A ligase (4CL) has been reported as a means for reducing lignin content in cell walls and increasing overall growth rates, thereby improving feedstock quality for paper and bioethanol production. Using hybrid poplar (Populus tremula...

Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease

PubMed Central

de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D.; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; Fernández, José M. García; Sánchez-Alcázar, José A.

2015-01-01

Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N’-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD. PMID:26045184

Seasonal variation of metabolism in lizard Phrynocephalus vlangalii at high altitude.

PubMed

Liang, Shiwei; Li, Weixin; Zhang, Yang; Tang, Xiaolong; He, Jianzheng; Bai, Yucheng; Li, Dongqin; Wang, Yan; Chen, Qiang

2017-01-01

Seasonal acclimatization is important for animals to live optimally in the varying environment. Phrynocephalus vlangalii, a species of lizard endemic in China, distributes on Qinghai-Tibet Plateau ranging from 2000 to 4600m above sea level. To dissect how this lizard mediate metabolism to adapt various season, the preferred body temperature (Tb), standard metabolic rate (SMR), mitochondrial respiration rates and activities of four metabolic enzymes in this species were tested in different seasons (spring, summer, and autumn). The results showed that the preferred Tb was the lowest in spring and the highest in summer. SMR, maximal mitochondrial respiration rates in liver and skeletal muscle were the highest in spring. Similarly, higher activities of lactate dehydrogenase (LDH), citrate synthase (CS) and cytochrome c oxidase (CCO) activities of liver and skeletal muscle were observed in spring. However, β-hydroxyacyl coenzyme A dehydrogenase (HOAD) activities of liver and skeletal muscle were higher in autumn. On the whole, seasonal variation of metabolism is the highest in spring and the lowest in summer. Seasonal variation of metabolism is the opposite of preferred body temperature, this may be one of the mechanisms to adapt to the environment in P. vlangalii. Our results suggested that P. vlangalii at high altitude has certain adaptive characteristics on metabolism in different seasons. Copyright © 2016 Elsevier Inc. All rights reserved.

Coq6 Is Responsible for the C4-deamination Reaction in Coenzyme Q Biosynthesis in Saccharomyces cerevisiae*

PubMed Central

Ozeir, Mohammad; Pelosi, Ludovic; Ismail, Alexandre; Mellot-Draznieks, Caroline; Fontecave, Marc; Pierrel, Fabien

2015-01-01

The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Δcoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway. PMID:26260787

Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.

PubMed

Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

2008-07-01

Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

Mild clinical manifestation and unusual recovery upon coenzyme Q₁₀ treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.

PubMed

Chen, Zhiting; Zhao, Zhenhua; Ye, Qinyong; Chen, Ying; Pan, Xiaodong; Sun, Bin; Huang, Huapin; Zheng, An

2015-03-01

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one‑year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

76 FR 36936 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... Certain Coenzyme Q10 Products and Methods of Making Same, DN 2822; the Commission is soliciting comments... importation of certain coenzyme Q10 products and method of making same. The complaint names as respondents...

Structural and biochemical characterization of cinnamoyl-coa reductases

USDA-ARS?s Scientific Manuscript database

Cinnamoyl-coenzyme A reductase (CCR) catalyzes the reduction of hydroxycinnamoyl-coenzyme A (CoA) esters using NADPH to produce hydroxycinnamyl aldehyde precursors in lignin synthesis. The catalytic mechanism and substrate specificity of cinnamoyl-CoA reductases from sorghum (Sorghum bicolor), a str...

Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study

PubMed Central

Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

2014-01-01

Background Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Material/Methods Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. Results The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (P<0.001). In the placebo group, PSS and PIS did not change. Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (−33.1% and −40.3%, respectively) in the Q10 group compared to placebo group (both P<0.05). From baseline, no differences in liver and muscle enzymes or cholesterol values were found. Conclusions The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities. PMID:25375075

Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.

PubMed

Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

2014-11-06

Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (P<0.001). In the placebo group, PSS and PIS did not change. Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo group (both P<0.05). From baseline, no differences in liver and muscle enzymes or cholesterol values were found. The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities.

Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model.

PubMed

Kesik, Vural; Yuksel, Ramazan; Yigit, Nuri; Saldir, Mehmet; Karabacak, Ercan; Erdem, Galip; Babacan, Oguzhan; Gulgun, Mustafa; Korkmazer, Nadir; Bayrak, Ziya

2016-09-01

Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL1β), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-α level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1β levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation. © The Author(s) 2015.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

PubMed

Zaki, Moushira E; El-Bassyouni, Hala T; Tosson, Angie M S; Youness, Eman; Hussein, Jihan

Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Fermentation of 1,2-Propanediol and 1,2-Ethanediol by Some Genera of Enterobacteriaceae, Involving Coenzyme B12-Dependent Diol Dehydratase

PubMed Central

Toraya, Tetsuo; Honda, Susumu; Fukui, Saburo

1979-01-01

Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 was able to grow anaerobically on 1,2-propanediol and 1,2-ethanediol as carbon and energy sources. Whole cells of the bacterium grown anaerobically on 1,2-propanediol or on glycerol catalyzed conversion of 1,2-diols and aldehydes to the corresponding acids and alcohols. Glucose-grown cells also converted aldehydes, but not 1,2-diols, to acids and alcohols. The presence of activities of coenzyme B12-dependent diol dehydratase, alcohol dehydrogenase, coenzyme-A-dependent aldehyde dehydrogenase, phosphotransacetylase, and acetate kinase was demonstrated with crude extracts of 1,2-propanediol-grown cells. The dependence of the levels of these enzymes on growth substrates, together with cofactor requirements in in vitro conversion of these substrates, indicates that 1,2-diols are fermented to the corresponding acids and alcohols via aldehydes, acyl-coenzyme A, and acyl phosphates. This metabolic pathway for 1,2-diol fermentation was also suggested in some other genera of Enterobacteriaceae which were able to grow anaerobically on 1,2-propanediol. When the bacteria were cultivated in a 1,2-propanediol medium not supplemented with cobalt ion, the coenzyme B12-dependent conversion of 1,2-diols to aldehydes was the rate-limiting step in this fermentation. This was because the intracellular concentration of coenzyme B12 was very low in the cells grown in cobalt-deficient medium, since the apoprotein of diol dehydratase was markedly induced in the cells grown in the 1,2-propanediol medium. Better cell yields were obtained when the bacteria were grown anaerobically on 1,2-propanediol. Evidence is presented that aerobically grown cells have a different metabolic pathway for utilizing 1,2-propanediol. PMID:378959

Gene encoding acetyl-coenzyme A carboxylase

DOEpatents

Roessler, Paul G.; Ohlrogge, John B.

1996-01-01

A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives thereof which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides.

Effects of α-Glycerophosphate and of Palmityl-Coenzyme A on Lipid Synthesis in Yeast Extracts

PubMed Central

White, David; Klein, Harold P.

1966-01-01

White, David (Ames Research Center, Moffett Field, Calif.), and Harold P. Klein. Effects of α-glycerophosphate and of palmityl-coenzyme A on lipid synthesis in yeast extracts. J. Bacteriol. 91:1218–1223. 1966.—The incorporation of acetate into fatty acids, but not into nonsaponifiable lipids, was stimulated by α-glycerophosphate in a supernatant fraction of Saccharomyces cerevisiae, obtained after centrifugation at 86,000 × g for 60 min. There was a pronounced effect at concentrations below 2 mm, but at concentrations above 5 mm α-glycerophosphate was relatively less stimulatory. α-Glycerophosphate markedly increased the percentage of esterified fatty acids among the products, and the formation of both saturated and unsaturated fatty acids was stimulated. Palmityl-coenzyme A inhibited fatty acid synthesis, affecting the formation of unsaturated acids more severely than saturated acids. In the presence of sufficient α-glycerophosphate to alleviate these inhibitions, palmityl-coenzyme A still reduced the formation of certain unsaturated fatty acids. PMID:5929752

Use of Limited Proteolysis and Mutagenesis To Identify Folding Domains and Sequence Motifs Critical for Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase Activity

PubMed Central

Villa, Juan A.; Cabezas, Matilde; de la Cruz, Fernando

2014-01-01

Triacylglycerols and wax esters are synthesized as energy storage molecules by some proteobacteria and actinobacteria under stress. The enzyme responsible for neutral lipid accumulation is the bifunctional wax ester synthase/acyl-coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT). Structural modeling of WS/DGAT suggests that it can adopt an acyl-CoA-dependent acyltransferase fold with the N-terminal and C-terminal domains connected by a helical linker, an architecture demonstrated experimentally by limited proteolysis. Moreover, we found that both domains form an active complex when coexpressed as independent polypeptides. The structural prediction and sequence alignment of different WS/DGAT proteins indicated catalytically important motifs in the enzyme. Their role was probed by measuring the activities of a series of alanine scanning mutants. Our study underscores the structural understanding of this protein family and paves the way for their modification to improve the production of neutral lipids. PMID:24296496

Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

PubMed

Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

2015-01-01

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

Targeting cellular energy production in neurological disorders.

PubMed

Baker, Steven K; Tarnopolsky, Mark A

2003-10-01

The concepts of energy dysregulation and oxidative stress and their complicated interdependence have rapidly evolved to assume primary importance in understanding the pathophysiology of numerous neurological disorders. Therefore, neuroprotective strategies addressing specific bioenergetic defects hold particular promise in the treatment of these conditions (i.e., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Friedreich's ataxia, mitochondrial cytopathies and other neuromuscular diseases), all of which, to some extent, share 'the final common pathway' leading to cell death through either necrosis or apoptosis. Compounds such as creatine monohydrate and coenzyme Q(10) offer substantial neuroprotection against ischaemia, trauma, oxidative damage and neurotoxins. Miscellaneous agents, including alpha-lipoic acid, beta-OH-beta-methylbutyrate, riboflavin and nicotinamide, have also been shown to improve various metabolic parameters in brain and/or muscle. This review will highlight the biological function of each of the above mentioned compounds followed by a discussion of their utility in animal models and human neurological disease. The balance of this work will be comprised of discussions on the therapeutic applications of creatine and coenzyme Q(10).

CINRG pilot trial of coenzyme Q10 in steroid-treated Duchenne muscular dystrophy.

PubMed

Spurney, Christopher F; Rocha, Carolina Tesi; Henricson, Erik; Florence, Julaine; Mayhew, Jill; Gorni, Ksenija; Pasquali, Livia; Pestronk, Alan; Martin, Gerard R; Hu, Fengming; Nie, Lei; Connolly, Anne M; Escolar, Diana M

2011-08-01

Corticosteroid treatment slows disease progression and is the standard of care for Duchenne muscular dystrophy (DMD). Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve function in dystrophin-deficient muscle. We performed an open-label, "add-on" pilot study of CoQ10 in thirteen 5-10-year-old DMD patients on steroids. The primary outcome measure was the total quantitative muscle testing (QMT) score. Twelve of 16 children (mean age 8.03 ± 1.64 years) completed the trial. Target serum levels of CoQ10 (≥2.5 μg/ml) were shown to be subject- and administration-dependent. Nine of 12 subjects showed an increase in total QMT score. Overall, CoQ10 treatment resulted in an 8.5% increase in muscle strength (P = 0.03). Addition of CoQ10 to prednisone therapy in DMD patients resulted in an increase in muscle strength. These results warrant a larger, controlled trial of CoQ10 in DMD. Copyright © 2011 Wiley Periodicals, Inc.

Nutritional recommendations for cardiovascular disease prevention.

PubMed

Eilat-Adar, Sigal; Sinai, Tali; Yosefy, Chaim; Henkin, Yaakov

2013-09-17

Lifestyle factors, including nutrition, play an important role in the etiology of Cardiovascular Disease (CVD). This position paper, written by collaboration between the Israel Heart Association and the Israel Dietetic Association, summarizes the current, preferably latest, literature on the association of nutrition and CVD with emphasis on the level of evidence and practical recommendations. The nutritional information is divided into three main sections: dietary patterns, individual food items, and nutritional supplements. The dietary patterns reviewed include low carbohydrate diet, low-fat diet, Mediterranean diet, and the DASH diet. Foods reviewed in the second section include: whole grains and dietary fiber, vegetables and fruits, nuts, soy, dairy products, alcoholic drinks, coffee and caffeine, tea, chocolate, garlic, and eggs. Supplements reviewed in the third section include salt and sodium, omega-3 and fish oil, phytosterols, antioxidants, vitamin D, magnesium, homocysteine-reducing agents, and coenzyme Q10.

Gene encoding acetyl-coenzyme A carboxylase

DOEpatents

Roessler, P.G.; Ohlrogge, J.B.

1996-09-24

A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives are disclosed which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides. 5 figs.

In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

PubMed

Giacone, Filippo; Condorelli, Rosita A; Mongioì, Laura M; Bullara, Valentina; La Vignera, Sandro; Calogero, Aldo E

2017-05-01

Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p < 0.01). This resulted in a significantly higher (p < 0.01) number of spermatozoa with progressive motility recovered after swim-up in both normozospermic men (4.1 ± 0.9 vs. 3.3 ± 1.0 millions) and asthenozooseprmic patients (3.2 ± 0.8 vs. 1.6 ± 0.5 millions). Finally, a statistically significant lower sperm lipid peroxidation was found after incubation with zinc, D-aspartic acid, and coenzyme-Q10 (p < 0.05) in both normozospermic men (1.0 ± 0.4 % vs. 2.4 ± 0.9 %) and asthenozooseprmic patients (0.2 ± 0.1 % vs. 0.6 ± 0.2 %). No statistically significant effect was observed on sperm DNA fragmentation. This nutraceutical formulation may be indicated in vitro during the separation of the spermatozoa in the assisted reproduction techniques, during which the spermatozoa undergo an increased oxidative stress.

Genetic Analysis of Comamonas acidovorans Polyhydroxyalkanoate Synthase and Factors Affecting the Incorporation of 4-Hydroxybutyrate Monomer

PubMed Central

Sudesh, Kumar; Fukui, Toshiaki; Doi, Yoshiharu

1998-01-01

The polyhydroxyalkanoate (PHA) synthase gene of Comamonas acidovorans DS-17 (phaCCa) was cloned by using the synthase gene of Alcaligenes eutrophus as a heterologous hybridization probe. Complete sequencing of a 4.0-kbp SmaI-HindIII (SH40) subfragment revealed the presence of a 1,893-bp PHA synthase coding region which was followed by a 1,182-bp β-ketothiolase gene (phaACa). Both the translated products of these genes showed significant identity, 51.1 and 74.2%, respectively, to the primary structures of the products of the corresponding genes in A. eutrophus. The arrangement of PHA biosynthesis genes in C. acidovorans was also similar to that in A. eutrophus except that the third gene, phaB, coding for acetoacetyl-coenzyme A reductase, was not found in the region downstream of phaACa. The cloned fragment complemented a PHA-negative mutant of A. eutrophus, PHB−4, resulting in poly-3-hydroxybutyrate accumulation of up to 73% of the dry cell weight when fructose was the carbon source. The heterologous expression enabled the incorporation of 4-hydroxybutyrate (4HB) and 3-hydroxyvalerate monomers. The PHA synthase of C. acidovorans does not appear to show any preference for 4-hydroxybutyryl-coenzyme A as a substrate. This leads to the suggestion that in C. acidovorans, it is the metabolic pathway, and not the specificity of the organism’s PHA synthase, that drives the incorporation of 4HB monomers, resulting in the efficient accumulation of PHA with a high 4HB content. PMID:9726894

Phylogenetic Relationships of Butyrate-Producing Bacteria from the Human Gut

PubMed Central

Barcenilla, Adela; Pryde, Susan E.; Martin, Jennifer C.; Duncan, Sylvia H.; Stewart, Colin S.; Henderson, Colin; Flint, Harry J.

2000-01-01

Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from three healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A second isolation was performed on the same three individuals 1 year later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. The results indicate very little overlap between the predominant ribotypes of the three subjects; furthermore, the flora of each individual changed significantly between the two isolations. Complete sequences of 16S rDNAs were determined for 24 representative strains and subjected to phylogenetic analysis. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-positive bacteria as defined by M. D. Collins et al. (Int. J. Syst. Bacteriol. 44:812–826, 1994) and A. Willems et al. (Int. J. Syst. Bacteriol. 46:195–199, 1996), with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl coenzyme A-acetyl coenzyme A transferase pathway for butyrate production. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate. PMID:10742256

Coenzyme Q and Mitochondrial Disease

ERIC Educational Resources Information Center

Quinzii, Catarina M.; Hirano, Michio

2010-01-01

Coenzyme Q[subscript 10] (CoQ[subscript 10]) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ[subscript 10] is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ[subscript…

Reduced wood stiffness and strength, and altered stem form, in young antisense 4CL transgenic poplars with reduced lignin contents

Treesearch

Steven L. Voelker; Barbara Lachenbruch; Frederick C. Meinzer; Peter Kitin; Steven H. Strauss

2011-01-01

Reduced lignin content in perennial crops has been sought as a means to improve biomass processability for paper and biofuels production, but it is unclear how this could affect wood properties and tree form. Here, we studied a nontransgenic control and 14 transgenic events containing an antisense 4-coumarate:coenzyme A ligase (4CL) to discern the...

Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: a long-term follow-up study.

PubMed

Haginoya, Kazuhiro; Miyabayashi, Shigeaki; Kikuchi, Masahiro; Kojima, Akira; Yamamoto, Katsuya; Omura, Kiyoshi; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Tanaka, Soichiro; Tsuchiya, Shigeru

2009-03-15

Respiratory failure can be the direct cause of death in patients with Leigh syndrome. Unfortunately, no effective treatment strategy is available. Here, we report successful treatment of a patient with Leigh syndrome using idebenone, a derivative of coenzyme Q-10. The patient's brainstem function, especially respiratory function, improved after idebenone treatment. Idebenone may be worth trying in patients with Leigh syndrome.

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study.

PubMed

Mustafa, Hesham N; El Awdan, Sally A; Hegazy, Gehan A; Abdel Jaleel, Gehad A

2015-01-01

The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity. Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically. Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA. It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study

PubMed Central

Mustafa, Hesham N.; El Awdan, Sally A.; Hegazy, Gehan A.; Abdel Jaleel, Gehad A.

2015-01-01

Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity. Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically. Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA. Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients. PMID:26729958

Skin Antiageing and Systemic Redox Effects of Supplementation with Marine Collagen Peptides and Plant-Derived Antioxidants: A Single-Blind Case-Control Clinical Study

PubMed Central

De Luca, Chiara; Mikhal'chik, Elena V.; Suprun, Maxim V.; Papacharalambous, Michael; Truhanov, Arseniy I.; Korkina, Liudmila G.

2016-01-01

Recently, development and research of nutraceuticals based on marine collagen peptides (MCPs) have been growing due to their high homology with human collagens, safety, bioavailability through gut, and numerous bioactivities. The major concern regarding safety of MCPs intake relates to increased risk of oxidative stress connected with collagen synthesis (likewise in fibrosis) and to ROS production by MCPs-stimulated phagocytes. In this clinical-laboratory study, fish skin MCPs combined with plant-derived skin-targeting antioxidants (AO) (coenzyme Q10 + grape-skin extract + luteolin + selenium) were administered to volunteers (n = 41). Skin properties (moisture, elasticity, sebum production, and biological age) and ultrasonic markers (epidermal/dermal thickness and acoustic density) were measured thrice (2 months before treatment and before and after cessation of 2-month oral intake). The supplementation remarkably improved skin elasticity, sebum production, and dermal ultrasonic markers. Metabolic data showed significant increase of plasma hydroxyproline and ATP storage in erythrocytes. Redox parameters, GSH/coenzyme Q10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within, however, normal range of values. Conclusions. A combination of MCPs with skin-targeting AOs could be effective and safe supplement to improve skin properties without risk of oxidative damage. PMID:26904164

A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study.

PubMed

Guilbot, Angèle; Bangratz, Marie; Ait Abdellah, Samira; Lucas, Christian

2017-08-30

Feverfew (Tanacetum parthenium L.), magnesium and coenzyme Q10 are frequently used for migraine prophylaxis. Supplementation with a fixed combination of these three agents (Antemig®, PiLeJe) was investigated in an observational study. Adult patients suffering from migraine according to the criteria of the International Headache Society were enrolled by general practitioners (≥2 migraine attacks during previous month; exclusion of chronic migraine and medication overuse) and after a one-month baseline phase, supplemented with one tablet of 100 mg feverfew, 100 mg coenzyme Q10 and 112.5 mg magnesium per day for 3 months. Supplementation significantly reduced the number of days with migraine headache during third month of supplementation compared to baseline phase (1.3 days ±1.5 versus 4.9 days ±2.6, p < 0.0001; n = 68 intention to treat; primary criterion). The decrease was progressive over the period of supplementation and significant from first month (1st month: -2.5 days ±3.1, p < 0.0001; 2nd month: -3 days ±2.8, p < 0.0001). The proportion of patients with a reduction of at least 50% in the number of days with migraine headache was 75% (51/68) after 3 months, with a progressive increase over the period of supplementation (63.2% [43/68] after 1 month and 70.6% [48/68] after 2 months). The proportion of patients with anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) decreased between baseline phase and third month of supplementation from 61.9% (39/63 patients with information available) to 35% (21/60) for depression and from 52.4% (33/63) to 30% (18/60) for anxiety. An improvement of quality of life (Qualité de Vie et Migraine questionnaire) was also observed. The combination was well tolerated. Results suggest that the proprietary supplement containing feverfew, coenzyme Q10 and magnesium assessed could be beneficial and safe for the prevention of migraine in adult patients and merits further study. ClinicalTrials.gov: NCT02901756 , retrospectively registered on August 24, 2016.

Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA.

PubMed

Weichler, Maria-Teresa; Kurteva-Yaneva, Nadya; Przybylski, Denise; Schuster, Judith; Müller, Roland H; Harms, Hauke; Rohwerder, Thore

2015-07-01

The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of thioesterase II, are discussed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Heterozygous Monocarboxylate Transporter 1 (MCT1, SLC16A1) Deficiency as a Cause of Recurrent Ketoacidosis.

PubMed

Balasubramaniam, Shanti; Lewis, Barry; Greed, Lawrence; Meili, David; Flier, Annegret; Yamamoto, Raina; Bilić, Karmen; Till, Claudia; Sass, Jörn Oliver

2016-01-01

We describe two half-siblings with monocarboxylate transporter 1 (MCT1, SLC16A1) deficiency, a defect on ketone body utilization, that has only recently been identified (van Hasselt et al., N Engl J Med, 371:1900-1907, 2014) as a cause for recurrent ketoacidoses. Our index patient is a boy with non-consanguineous parents who had presented acutely with impaired consciousness and severe metabolic ketoacidosis following a 3-day history of gastroenteritis at age 5 years. A 12.5-year-old half-brother who shared the proband's mother also had a previous history of recurrent ketoacidoses. Results of mutation and enzyme activity analyses in proband samples advocated against methylacetoacetyl-coenzyme A thiolase ("beta-ketothiolase") and succinyl-coenzyme A: 3-oxoacyl coenzyme A transferase (SCOT) deficiencies. A single heterozygous c.982C>T transition in the SLC16A1 gene resulting in a stop mutation (p.Arg328Ter) was detected in both boys. It was shared by their healthy mother and by the proband's half-sister, but was absent in the proband's father. MCT1 deficiency may be more prevalent than is apparent, as clinical manifestations can occur both in individuals with bi- and monoallelic mutations. It may be an important differential diagnosis in recurrent ketoacidosis with or without hypoglycemia, particularly in the absence of any specific metabolic profiles in blood and urine. Early diagnosis may enable improved disease management. Careful identification of potential triggers of metabolic decompensations in individuals even with single heterozygous mutations in the SLC16A1 gene is indicated.

Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions

PubMed Central

Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

2008-01-01

Background and purpose: Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Experimental approach: Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Key results: Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Conclusion and implications: Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions. PMID:18587443

Menaquinone analogs inhibit growth of bacterial pathogens.

PubMed

Schlievert, Patrick M; Merriman, Joseph A; Salgado-Pabón, Wilmara; Mueller, Elizabeth A; Spaulding, Adam R; Vu, Bao G; Chuang-Smith, Olivia N; Kohler, Petra L; Kirby, John R

2013-11-01

Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.

Function of Coenzyme F420 in Aerobic Catabolism of 2,4,6-Trinitrophenol and 2,4-Dinitrophenol by Nocardioides simplex FJ2-1A

PubMed Central

Ebert, Sybille; Rieger, Paul-Gerhard; Knackmuss, Hans-Joachim

1999-01-01

2,4,6-Trinitrophenol (picric acid) and 2,4-dinitrophenol were readily biodegraded by the strain Nocardioides simplex FJ2-1A. Aerobic bacterial degradation of these π-electron-deficient aromatic compounds is initiated by hydrogenation at the aromatic ring. A two-component enzyme system was identified which catalyzes hydride transfer to picric acid and 2,4-dinitrophenol. Enzymatic activity was dependent on NADPH and coenzyme F420. The latter could be replaced by an authentic preparation of coenzyme F420 from Methanobacterium thermoautotrophicum. One of the protein components functions as a NADPH-dependent F420 reductase. A second component is a hydride transferase which transfers hydride from reduced coenzyme F420 to the aromatic system of the nitrophenols. The N-terminal sequence of the F420 reductase showed high homology with an F420-dependent NADP reductase found in archaea. In contrast, no N-terminal similarity to any known protein was found for the hydride-transferring enzyme. PMID:10217752

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Functional contribution of coenzyme specificity-determining sites of 7α-hydroxysteroid dehydrogenase from Clostridium absonum.

PubMed

Lou, Deshuai; Wang, Yue; Tan, Jun; Zhu, Liancai; Ji, Shunlin; Wang, Bochu

2017-10-01

Studies of the molecular determinants of coenzyme specificity help to reveal the structure-function relationship of enzymes, especially with regards to coenzyme specificity-determining sites (CSDSs) that usually mediate complex interactions. NADP(H)-dependent 7α-hydroxysteroid dehydrogenase from Clostridium absonum (CA 7α-HSDH), a member of the short-chain dehydrogenase/reductase superfamily (SDRs), possesses positively charged CSDSs that mainly contain T15, R16, R38, and R194, forming complicated polar interactions with the adenosine ribose C2 phosphate group of NADP(H). The R38 residue is crucial for coenzyme anchoring, but the influence of the other residues on coenzyme utilization is still not clear. Hence, we performed alanine scanning mutagenesis and molecular dynamic (MD) simulations. The results suggest that the natural CSDSs have the greatest NADP(H)-binding affinity, but not the best activity (k cat ) toward NADP + . Compared with the wild type and other mutants, the mutant R194A showed the highest catalytic efficiency (k cat /K m ), which was more than three-times that of the wild type. MD simulation and kinetics analysis suggested that the importance of the CSDSs of CA 7α-HSDH should be in accordance with the following order R38>T15>R16>R194, and S39 may have a supporting role in NADP(H) anchoring for mutants R16A/T194A and T15A/R16A/T194A. Copyright © 2017. Published by Elsevier Ltd.

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

PubMed Central

Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

2017-01-01

Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed. PMID:28609475

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

PubMed

Alehagen, Urban; Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

2017-01-01

Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.

Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats

PubMed Central

Cai, Charles L.; Henry, Michael M.; Chowdhury, Sara; Valencia, Gloria B.; Aranda, Jacob V.

2017-01-01

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or n-3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O2 with brief hypoxic episodes (12% O2); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only from P0 to P14. Pups were studied at P14 or placed in RA until P21 for recovery from IH (IHR). Body weight and length; organ weights; and serum antioxidants and growth factors were determined at P14 and P21. Neonatal IH resulted in sustained reductions in somatic growth, an effect that was reversed with n-3 PUFAs. Improved growth was associated with higher serum growth factors. CoQ10 decreased superoxide dismutase (SOD) and glutathione, but increased catalase, suggesting reduced oxidative stress. Further studies are needed to determine the synergistic effects of CoQ10 and n-3 PUFA co-administration for the prevention of IH-induced oxidative stress and postnatal growth deficits. PMID:29258174

Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats.

PubMed

Beharry, Kay D; Cai, Charles L; Henry, Michael M; Chowdhury, Sara; Valencia, Gloria B; Aranda, Jacob V

2017-12-16

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or n -3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O₂ with brief hypoxic episodes (12% O₂); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, n -3 PUFAs in fish oil, or olive oil only from P0 to P14. Pups were studied at P14 or placed in RA until P21 for recovery from IH (IHR). Body weight and length; organ weights; and serum antioxidants and growth factors were determined at P14 and P21. Neonatal IH resulted in sustained reductions in somatic growth, an effect that was reversed with n -3 PUFAs. Improved growth was associated with higher serum growth factors. CoQ10 decreased superoxide dismutase (SOD) and glutathione, but increased catalase, suggesting reduced oxidative stress. Further studies are needed to determine the synergistic effects of CoQ10 and n -3 PUFA co-administration for the prevention of IH-induced oxidative stress and postnatal growth deficits.

Mechanism of Rifampicin Inactivation in Nocardia farcinica

PubMed Central

Abdelwahab, Heba; Martin Del Campo, Julia S.; Dai, Yumin; Adly, Camelia; El-Sohaimy, Sohby; Sobrado, Pablo

2016-01-01

A novel mechanism of rifampicin (Rif) resistance has recently been reported in Nocardia farcinica. This new mechanism involves the activity of rifampicin monooxygenase (RifMO), a flavin-dependent monooxygenase that catalyzes the hydroxylation of Rif, which is the first step in the degradation pathway. Recombinant RifMO was overexpressed and purified for biochemical analysis. Kinetic characterization revealed that Rif binding is necessary for effective FAD reduction. RifMO exhibits only a 3-fold coenzyme preference for NADPH over NADH. RifMO catalyzes the incorporation of a single oxygen atom forming an unstable intermediate that eventually is converted to 2′-N-hydroxy-4-oxo-Rif. Stable C4a-hydroperoxyflavin was not detected by rapid kinetics methods, which is consistent with only 30% of the activated oxygen leading to product formation. These findings represent the first reported detailed biochemical characterization of a flavin-monooxygenase involved in antibiotic resistance. PMID:27706151

Nutraceuticals in Acute and Prophylactic Treatment of Migraine.

PubMed

Daniel, Oved; Mauskop, Alexander

2016-04-01

People who suffer from headaches often prefer nutraceutical treatment over traditional pharmacological approaches, due to fear of possible side effects, drug dependence, or addiction. Since treatment with nutraceuticals does not require a doctor's prescription, many patients rely on their own judgment as to when and which one to take, often without consultation or guidance from their physician. Some physicians could provide information about potential efficacy and side effects of various products, but many are not familiar with the nutraceuticals. Widespread skepticism persists among doctors about the effectiveness of these treatments. This is largely due to the lack of rigorous clinical studies. However, even when incontrovertible scientific evidence exists, many physicians remain distrustful of the evidence. The following review summarizes randomized controlled trials of some of the most commonly used non-pharmacological treatments, including magnesium, coenzyme Q10, riboflavin (vitamin B2), petasites, and feverfew (Table 1).

Nutritional Recommendations for Cardiovascular Disease Prevention

PubMed Central

Eilat-Adar, Sigal; Sinai, Tali; Yosefy, Chaim; Henkin, Yaakov

2013-01-01

Lifestyle factors, including nutrition, play an important role in the etiology of Cardiovascular Disease (CVD). This position paper, written by collaboration between the Israel Heart Association and the Israel Dietetic Association, summarizes the current, preferably latest, literature on the association of nutrition and CVD with emphasis on the level of evidence and practical recommendations. The nutritional information is divided into three main sections: dietary patterns, individual food items, and nutritional supplements. The dietary patterns reviewed include low carbohydrate diet, low-fat diet, Mediterranean diet, and the DASH diet. Foods reviewed in the second section include: whole grains and dietary fiber, vegetables and fruits, nuts, soy, dairy products, alcoholic drinks, coffee and caffeine, tea, chocolate, garlic, and eggs. Supplements reviewed in the third section include salt and sodium, omega-3 and fish oil, phytosterols, antioxidants, vitamin D, magnesium, homocysteine-reducing agents, and coenzyme Q10. PMID:24067391

Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch

USDA-ARS?s Scientific Manuscript database

Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate Coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil (RBO), and incorporated into an aqueous OSA-ST solution. High pressure homogenization (HPH) of the mixture was conducted at 170 MPa for 5-6 cycles. The resulting ...

Regulation of 4CL, encoding 4-coumarate: coenzyme A ligase, expression in kenaf under diverse stress conditions

USDA-ARS?s Scientific Manuscript database

We cloned the full length 4CL ortholog encoding 4-coumarate: coenzymeA ligase from kenaf (Hibiscus cannabiuns) using degenerate primers and RACE (rapid amplification of cDNA ends) systems. The 4CL is a key regulatory enzyme of the phenylpropanoid pathway that regulates the activation of cinnamic ac...

Hypolipidemic, anti-obesity, anti-inflammatory, anti-osteoporotic, and anti-neoplastic properties of amine carboxyboranes.

PubMed Central

Hall, I H; Chen, S Y; Rajendran, K G; Sood, A; Spielvogel, B F; Shih, J

1994-01-01

The amine-carboxyborane derivatives were shown to be effective antineoplastic/cytotoxic agents with selective activity against single-cell and solid tumors derived from murine and human leukemias, lymphomas, sarcomas, and carcinomas. The agents inhibited DNA and RNA synthesis in preference to protein synthesis in L1210 lymphoid leukemia cells. Inosine-monophosphate dehydrogenase apparently is a target site of the compounds; similar effects on phosphoribosyl-pyrophosphate amido transferase, orotidine-monophosphate decarboxylase, and both nucleoside and nucleotide kinases were observed. Deoxyribonucleotide pool levels were reduced in the cells; DNA strand scission was observed with the agents. In rodents, the amine carboxyboranes were potent hypolipidemic agents, lowering both serum cholesterol and triglyceride concentrations, in addition to lowering cholesterol content of very low-density lipoprotein and low-density lipoprotein (LDL) and elevating high-density lipoprotein (HDL) cholesterol concentrations. De novo regulatory enzymes involved in lipid synthesis were also inhibited (e.g., hypocholesterolemic 3-hydroxy-3-methyl-Coenzyme A reductase, acyl-Coenzyme A cholesterol acyltransferase, and sn-glycerol-3-phosphate acyltransferase). Concurrently, the agents modulated LDL and HDL receptor binding, internalization, and degradation, so that less cholesterol was delivered to the plaques and more broken down from esters and conducted to the liver for biliary excretion. Tissue lipids in the aorta wall of the rat were reduced and fewer atherosclerotic morphologic lesions were present in quail aortas after treatment with the agents. Cholesterol resorption from the rat intestine was reduced in the presence of drug. Genetic hyperlipidemic mice demonstrated the same types of reduction after treatment with the agents. The agents would effectively lower lipids in tissue based on the inhibition of regulatory enzymes in pigs. These findings should help improve domestic meat supplies from fowl and pigs. The amine-carboxyboranes were effective anti-inflammatory agents against septic shock, induced edema, pleurisy, and chronic arthritis at 2.5 to 8 mg/kg. Lysosomal and proteolytic enzyme activities were also inhibited. More significantly, the agents were dual inhibitors of prostaglandin cyclooxygenase and 5'-lipoxygenase activities. These compounds also affected cytokine release and white cell migration. Subsequent studies showed that the amine-carboxyboranes were potent anti-osteoporotic agents reducing calcium resorption as well as increasing calcium and proline incorporation into mouse pup calvaria and rat UMR-106 collagen. PMID:7889876

Effect of a 5-mo nutritional intervention on nutritional status and quality of life for patient with 3-hydroxyisobutyryl-coenzyme A hydrolase deficiency: A case report.

PubMed

Li, Chun-Wei; Yu, Kang; Xu, Yan; Sun, Xia-Yuan; Li, Rong-Rong; Wang, Fang

2015-01-01

3-Hydroxy-isobutyryl-coenzyme A (CoA) hydrolase (HBICH) deficiency is a rare cerebral organic aciduria caused by disturbance of valine catabolism that leads to the accumulation of toxic metabolites, methacrylyl-CoA. The major feature exhibited by a patient with HBICH deficiency includes multiple congenital malformations and abnormal neurologic findings. However, the pathophysiology of this disease remains unknown. The major treatment for HBICH deficiency involves a low-protein diet, especially restricting valine, supplemented with micronutrients and carnitine. To our knowledge, only four patients with HBICH deficiency have been reported. These patients were boys and presented with different clinical, biochemical, and genetic features than our patient. In this report, we described what was to our knowledge the first genetically confirmed girl with HBICH deficiency in China. A 5-mo nutritional intervention was given to the patient by a nutritional support team. On this regimen, the patient's symptoms were alleviated and her quality of life was improved. Copyright © 2015 Elsevier Inc. All rights reserved.

An enhanced chemoenzymatic method for loading substrates onto carrier protein domains.

PubMed

Kittilä, Tiia; Cryle, Max J

2018-06-01

Non-ribosomal peptide synthetase (NRPS) machineries produce many medically relevant peptides that cannot be easily accessed by chemical synthesis. Thus, understanding NRPS mechanism is of crucial importance to allow efficient redesign of these machineries to produce new compounds. During NRPS-mediated synthesis, substrates are covalently attached to peptidyl carrier proteins (PCPs), and studies of NRPSs are impeded by difficulties in producing PCPs loaded with substrates. Different approaches to load substrates onto PCP domains have been described, but all suffer from difficulties in either the complexity of chemical synthesis or low enzymatic efficiency. Here, we describe an enhanced chemoenzymatic loading method that combines 2 approaches into a single, highly efficient one-pot loading reaction. First, d-pantetheine and ATP are converted into dephospho-coenzyme A via the actions of 2 enzymes from coenzyme A (CoA) biosynthesis. Next, phosphoadenylates are dephosphorylated using alkaline phosphatase to allow linker attachment to PCP domain by Sfp mutant R4-4, which is inhibited by phosphoadenylates. This route does not depend on activity of the commonly problematic dephospho-CoA kinase and, therefore, offers an improved method for substrate loading onto PCP domains.

Microemulsions based on a sunflower lecithin-Tween 20 blend have high capacity for dissolving peppermint oil and stabilizing coenzyme Q10.

PubMed

Chen, Huaiqiong; Guan, Yongguang; Zhong, Qixin

2015-01-28

The objectives of the present study were to improve the capability of microemulsions to dissolve peppermint oil by blending sunflower lecithin with Tween 20 and to study the possibility of codelivering lipophilic bioactive compounds. The oil loading in microemulsions with 20% (w/w) Tween 20 increased from 3% (w/w) to 20% (w/w) upon gradual supplementation of 6% (w/w) lecithin. All microemulsions had particles of <12 nm that did not change over 70 d of storage at 21 °C. They had relatively low Newtonian viscosities and were physically and chemically stable after 50-200-fold dilution in water, resulting from similar hydrophile-lipophile-balance values of the surfactant mixture and peppermint oil. Furthermore, the microemulsions were capable of dissolving coenzyme Q10 and preventing its degradation at UV 302 nm, more significant for the microemulsion with lecithin. Therefore, natural surfactant lecithin can reduce the use of synthetic Tween 20 to dissolve peppermint oil and protect the degradation of dissolved lipophilic bioactive components in transparent products.

Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q Production.

PubMed

Veling, Mike T; Reidenbach, Andrew G; Freiberger, Elyse C; Kwiecien, Nicholas W; Hutchins, Paul D; Drahnak, Michael J; Jochem, Adam; Ulbrich, Arne; Rush, Matthew J P; Russell, Jason D; Coon, Joshua J; Pagliarini, David J

2017-12-07

Mitoproteases are becoming recognized as key regulators of diverse mitochondrial functions, although their direct substrates are often difficult to discern. Through multi-omic profiling of diverse Saccharomyces cerevisiae mitoprotease deletion strains, we predicted numerous associations between mitoproteases and distinct mitochondrial processes. These include a strong association between the mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis-a pathway essential for mitochondrial respiration. Through Edman sequencing and in vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the N terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves its stability. A single mutation to the Oct1p recognition motif in Coq5p disrupted its processing in vivo, leading to CoQ deficiency and respiratory incompetence. This work defines the Oct1p processing of Coq5p as an essential post-translational event for proper CoQ production. Additionally, our data visualization tool enables efficient exploration of mitoprotease profiles that can serve as the basis for future mechanistic investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Sphingolipid Long-Chain Base Synthesis in Plants (Characterization of Serine Palmitoyltransferase Activity in Squash Fruit Microsomes).

PubMed

Lynch, D. V.; Fairfield, S. R.

1993-12-01

The activity of serine palmitoyltransferase (palmitoyl-coenzyme A [CoA]:L-serine [Ser]-C-palmitoyltransferase [decarboxylating], EC 2.3.1.50), the enzyme catalyzing the first step in the synthesis of the long-chain base required for sphingolipid assembly, has been characterized in a plant system. Enzyme activity in a microsomal membrane fraction from summer squash fruit (Cucurbita pepo L. cv Early Prolific Straightneck) was assayed by monitoring the incorporation of L-[3H]Ser into the chloroform-soluble product, 3-ketosphinganine. Addition of NADPH to the assay system resulted in the conversion of 3-ketosphinganine to sphinganine. The apparent Km for Ser was approximately 1.8 mM. The enzyme exhibited a strong preference for palmitoyl-CoA, with optimal activity at a substrate concentration of 200 [mu]M. Pyridoxal 5[prime]-phosphate was required as a coenzyme. The pH optimum was 7.6, and the temperature optimum was 36 to 40[deg]C. Enzyme activity was greatest in the microsomal fraction obtained by differential centrifugation and was localized to the endoplasmic reticulum using marker enzymes. Two known mechanism-based inhibitors of the mammalian enzyme, L-cycloserine and [beta]-chloro-L-alanine, were effective inhibitors of enzyme activity in squash microsomes. Changes in enzyme activity with size (age) of squash fruit were observed. The results from this study suggest that the properties and catalytic mechanism of Ser palmitoyltransferase from squash are similar to those of the animal, fungal, and bacterial enzyme in most respects. The specific activity of the enzyme in squash microsomes ranged from 0.57 to 0.84 nmol min-1 mg-1 of protein, values 2- to 20-fold higher than those previously reported for preparations from animal tissues.

Oxalyl-Coenzyme A Reduction to Glyoxylate Is the Preferred Route of Oxalate Assimilation in Methylobacterium extorquens AM1

PubMed Central

Schneider, Kathrin; Skovran, Elizabeth

2012-01-01

Oxalate catabolism is conducted by phylogenetically diverse organisms, including Methylobacterium extorquens AM1. Here, we investigate the central metabolism of this alphaproteobacterium during growth on oxalate by using proteomics, mutant characterization, and 13C-labeling experiments. Our results confirm that energy conservation proceeds as previously described for M. extorquens AM1 and other characterized oxalotrophic bacteria via oxalyl-coenzyme A (oxalyl-CoA) decarboxylase and formyl-CoA transferase and subsequent oxidation to carbon dioxide via formate dehydrogenase. However, in contrast to other oxalate-degrading organisms, the assimilation of this carbon compound in M. extorquens AM1 occurs via the operation of a variant of the serine cycle as follows: oxalyl-CoA reduction to glyoxylate and conversion to glycine and its condensation with methylene-tetrahydrofolate derived from formate, resulting in the formation of C3 units. The recently discovered ethylmalonyl-CoA pathway operates during growth on oxalate but is nevertheless dispensable, indicating that oxalyl-CoA reductase is sufficient to provide the glyoxylate required for biosynthesis. Analysis of an oxalyl-CoA synthetase- and oxalyl-CoA-reductase-deficient double mutant revealed an alternative, although less efficient, strategy for oxalate assimilation via one-carbon intermediates. The alternative process consists of formate assimilation via the tetrahydrofolate pathway to fuel the serine cycle, and the ethylmalonyl-CoA pathway is used for glyoxylate regeneration. Our results support the notion that M. extorquens AM1 has a plastic central metabolism featuring multiple assimilation routes for C1 and C2 substrates, which may contribute to the rapid adaptation of this organism to new substrates and the eventual coconsumption of substrates under environmental conditions. PMID:22493020

Eighty routes to a ribonucleotide world; dispersion and stringency in the decisive selection.

PubMed

Yarus, Michael

2018-05-21

We examine the initial emergence of genetics; that is, of an inherited chemical capability. The crucial actors are ribonucleotides, occasionally meeting in a prebiotic landscape. Previous work identified six influential variables during such random ribonucleotide pooling. Geochemical pools can be in periodic danger (e.g., from tides) or constant danger (e.g., from unfavorable weather). Such pools receive Gaussian nucleotide amounts sporadically, at random times, or get varying substrates simultaneously. Pools use cross-templated RNA synthesis (5'-5' product from 5'-3' template) or para-templated (5'-5' product from 5'-5' template) synthesis. Pools can undergo mild or strong selection, and be recently initiated (early) or late in age. Considering > 80 combinations of these variables, selection calculations identify a superior route. Most likely, an early, sporadically fed, cross-templating pool in constant danger, receiving ≥ 1 mM nucleotides while under strong selection for a coenzyme-like product will host selection of the first encoded biochemical functions. Predominantly templated products emerge from a critical event, the starting bloc selection, which exploits inevitable differences among early pools. Favorable selection has a simple rationale; it is increased by product dispersion (sd/mean), by selection intensity (mild or strong), or by combining these factors as stringency, reciprocal fraction of pools selected (1/sfsel). To summarize: chance utility, acting via a preference for disperse, templated coenzyme-like dinucleotides, uses stringent starting bloc selection to quickly establish majority encoded/genetic expression. Despite its computational origin, starting bloc selection is largely independent of specialized assumptions. This ribodinucleotide route to inheritance may also have facilitated 5'-3' chemical RNA replication. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Differential Expression of Biphenyl Synthase Gene Family Members in Fire-Blight-Infected Apple ‘Holsteiner Cox’ 1[W][OA

PubMed Central

Chizzali, Cornelia; Gaid, Mariam M.; Belkheir, Asma K.; Hänsch, Robert; Richter, Klaus; Flachowsky, Henryk; Peil, Andreas; Hanke, Magda-Viola; Liu, Benye; Beerhues, Ludger

2012-01-01

Fire blight, caused by the bacterium Erwinia amylovora, is a devastating disease of apple (Malus × domestica). The phytoalexins of apple are biphenyls and dibenzofurans, whose carbon skeleton is formed by biphenyl synthase (BIS), a type III polyketide synthase. In the recently published genome sequence of apple ‘Golden Delicious’, nine BIS genes and four BIS gene fragments were detected. The nine genes fall into four subfamilies, referred to as MdBIS1 to MdBIS4. In a phylogenetic tree, the BIS amino acid sequences from apple and Sorbus aucuparia formed an individual cluster within the clade of the functionally diverse type III polyketide synthases. cDNAs encoding MdBIS1 to MdBIS4 were cloned from fire-blight-infected shoots of apple ‘Holsteiner Cox,’ heterologously expressed in Escherichia coli, and functionally analyzed. Benzoyl-coenzyme A and salicoyl-coenzyme A were the preferred starter substrates. In response to inoculation with E. amylovora, the BIS3 gene was expressed in stems of cv Holsteiner Cox, with highest transcript levels in the transition zone between necrotic and healthy tissues. The transition zone was the accumulation site of biphenyl and dibenzofuran phytoalexins. Leaves contained transcripts for BIS2 but failed to form immunodetectable amounts of BIS protein. In cell cultures of apple ‘Cox Orange,’ expression of the BIS1 to BIS3 genes was observed after the addition of an autoclaved E. amylovora suspension. Using immunofluorescence localization under a confocal laser-scanning microscope, the BIS3 protein in the transition zone of stems was detected in the parenchyma of the bark. Dot-shaped immunofluorescence was confined to the junctions between neighboring cortical parenchyma cells. PMID:22158676

Coenzyme Q10: A New Treatment for Hemorrhagic Shock

DTIC Science & Technology

2014-10-29

SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

Critical assessment of various techniques for the extraction of carotenoids and co-enzyme Q10 from the Thraustochytrid strain ONC-T18.

PubMed

Armenta, Roberto E; Burja, Adam; Radianingtyas, Helia; Barrow, Colin J

2006-12-27

A variety of techniques for extracting carotenoids from the marine Thraustochytrium sp. ONC-T18 was compared. Specifically, the organic solvents acetone, ethyl acetate, and petroleum ether were tested, along with direct and indirect ultrasonic assisted extraction (probe vs bath) methods. Techniques that used petroleum ether/acetone/water (15:75:10, v/v/v) with 3 h of agitation, or 5 min in an ultrasonic bath, produced the highest extraction yields of total carotenoids (29-30.5 microg g-1). Concentrations up to 11.5 microg g-1 of canthaxanthin and 17.5 microg g-1 of beta;-carotene were detected in extracts stored for 6 weeks. Astaxanthin and echinenone were also detected as minor compounds. Extracts with and without antioxidants showed similar carotenoid concentration profiles. However, total carotenoid concentrations were approximately 8% higher when antioxidants were used. Finally, an easy-to-perform and inexpensive method to detect co-enzymes in ONC-T18 was also developed using silica gel TLC plates. Five percent methanol in toluene as a mobile phase consistently eluted co-enzyme Q10 standards and could separate the co-enzyme fractions present in ONC-T18.

Donor-Acceptor Distance Sampling Enhances the Performance of "Better than Nature" Nicotinamide Coenzyme Biomimetics.

PubMed

Geddes, Alexander; Paul, Caroline E; Hay, Sam; Hollmann, Frank; Scrutton, Nigel S

2016-09-07

Understanding the mechanisms of enzymatic hydride transfer with nicotinamide coenzyme biomimetics (NCBs) is critical to enhancing the performance of nicotinamide coenzyme-dependent biocatalysts. Here the temperature dependence of kinetic isotope effects (KIEs) for hydride transfer between "better than nature" NCBs and several ene reductase biocatalysts is used to indicate transfer by quantum mechanical tunneling. A strong correlation between rate constants and temperature dependence of the KIE (ΔΔH(⧧)) for H/D transfer implies that faster reactions with NCBs are associated with enhanced donor-acceptor distance sampling. Our analysis provides the first mechanistic insight into how NCBs can outperform their natural counterparts and emphasizes the need to optimize donor-acceptor distance sampling to obtain high catalytic performance from H-transfer enzymes.

Small-Angle X-Ray Scattering Analysis of the Bifunctional Antibiotic Resistance Enzyme Aminoglycoside (6′) Acetyltransferase-Ie/Aminoglycoside (2″) Phosphotransferase-Ia Reveals a Rigid Solution Structure

PubMed Central

Caldwell, Shane J.

2012-01-01

Aminoglycoside (6′) acetyltransferase-Ie/aminoglycoside (2″) phosphotransferase-Ia [AAC(6′)-Ie/APH(2″)-Ia] is one of the most problematic aminoglycoside resistance factors in clinical pathogens, conferring resistance to almost every aminoglycoside antibiotic available to modern medicine. Despite 3 decades of research, our understanding of the structure of this bifunctional enzyme remains limited. We used small-angle X-ray scattering (SAXS) to model the structure of this bifunctional enzyme in solution and to study the impact of substrate binding on the enzyme. It was observed that the enzyme adopts a rigid conformation in solution, where the N-terminal AAC domain is fixed to the C-terminal APH domain and not loosely tethered. The addition of acetyl-coenzyme A, coenzyme A, GDP, guanosine 5′-[β,γ-imido]triphosphate (GMPPNP), and combinations thereof to the protein resulted in only modest changes to the radius of gyration (RG) of the enzyme, which were not consistent with any large changes in enzyme structure upon binding. These results imply some selective advantage to the bifunctional enzyme beyond coexpression as a single polypeptide, likely linked to an improvement in enzymatic properties. We propose that the rigid structure contributes to improved electrostatic steering of aminoglycoside substrates toward the two active sites, which may provide such an advantage. PMID:22290965

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial high-energy phosphate metabolism in men.

PubMed

Schocke, Michael F; Martinek, Martin; Kremser, Christian; Wolf, Christian; Steinboeck, Peter; Lechleitner, Monika; Jaschke, Werner; Pachinger, Otmar; Metzler, Bernhard

2003-01-01

We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins have a beneficial impact on the human myocardial, high-energy, phosphate metabolism. The present study included 18 male patients (mean age 49.8 +/- 10.3) with statin-treated, familiar hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6 +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/- 12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium. Furthermore, echocardiographic evaluation and stress tests were performed in all individuals. The untreated patients with FH exhibited a significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34) compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios of the treated FH patients were in the range of the healthy controls. Our study shows for the first time an-improvement of the high-energy, phosphate metabolism in the left ventricular myocardium of patients with statin-treated FH compared with untreated FH patients.

Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

PubMed

Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

2011-12-01

Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

Precision breeding for RNAi suppression of a major 4-coumarate:coenzyme A ligase gene improves cell wall saccharification from field grown sugarcane.

PubMed

Jung, Je Hyeong; Kannan, Baskaran; Dermawan, Hugo; Moxley, Geoffrey W; Altpeter, Fredy

2016-11-01

Sugarcane (Saccharum spp. hybrids) is a major feedstock for commercial bioethanol production. The recent integration of conversion technologies that utilize lignocellulosic sugarcane residues as well as sucrose from stem internodes has elevated bioethanol yields. RNAi suppression of lignin biosynthetic enzymes is a successful strategy to improve the saccharification of lignocellulosic biomass. 4-coumarate:coenzyme A ligase (4CL) is a key enzyme in the biosynthesis of phenylpropanoid metabolites, such as lignin and flavonoids. Identifying a major 4CL involved in lignin biosynthesis among multiple isoforms with functional divergence is key to manipulate lignin biosynthesis. In this study, two full length 4CL genes (Sh4CL1 and Sh4CL2) were isolated and characterized in sugarcane. Phylogenetic, expression and RNA interference (RNAi) analysis confirmed that Sh4CL1 is a major lignin biosynthetic gene. An intragenic precision breeding strategy may facilitate the regulatory approval of the genetically improved events and was used for RNAi suppression of Sh4CL1. Both, the RNAi inducing cassette and the expression cassette for the mutated ALS selection marker consisted entirely of DNA sequences from sugarcane or the sexually compatible species Sorghum bicolor. Field grown sugarcane with intragenic RNAi suppression of Sh4CL1 resulted in reduction of the total lignin content by up to 16.5 % along with altered monolignol ratios without reduction in biomass yield. Mature, field grown, intragenic sugarcane events displayed 52-76 % improved saccharification efficiency of lignocellulosic biomass compared to wild type (WT) controls. This demonstrates for the first time that an intragenic approach can add significant value to lignocellulosic feedstocks for biofuel and biochemical production.

Mechanism of α-Glycerophosphate Regulation of Acetyl-Coenzyme A Carboxylase of Saccharomyces cerevisiae

PubMed Central

Rasmussen, Roberta K.; Klein, Harold P.

1968-01-01

The mechanism proposed for the activation of animal acetyl-coenzyme A (CoA) carboxylase by α-glycerophosphate, namely, the removal of inhibitory palmityl-CoA via glyceride synthesis, is not the only possible one in the yeast system because extracts exhibiting marked stimulation of acetyl-CoA carboxylase activity by α-glyerophosphate show a lack of acyl-CoA compounds. PMID:5643049

Comparative bioavailability of two novel coenzyme Q10 preparations in humans.

PubMed

Joshi, S S; Sawant, S V; Shedge, A; Halpner, A D

2003-01-01

To determine the absorptive properties of 2 novel coenzyme Q10 preparations, a fast-melting tablet and an effervescent tablet, compared with currently available formulations. In the first trial, the absorptive properties of 4 different coenzyme Q10 preparations (fast-melting, effervescent, soft gelatin, and powder-filled hard shell) were studied in a randomized, single-dose, crossover study. Twenty-four male subjects were given a 60 mg dose of coenzyme Q10 and plasma coenzyme Q10 was measured over the next 12 hours. Pharmacokinetic properties including area under the curve (AUC), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (t 1/2) were measured. In a separate single-dose study, the absorptive characteristics of a different coenzyme Q10 soft gel (Q-Gel) were studied in 6 male subjects. Area under the curve (microg/ml x h) for the fast-melting and effervescent formulations, while marginally greater, was not significantly different when compared to the soft gelatin and powder-filled preparations, 5.4 +/- 1.04 (110%) and 5.5 +/- 0.589 (112%) versus 5.0 +/- 0.859 (102%) and 4.9 +/- 0.812 (100%), respectively. Cmax for the 2 novel formulations was also not statistically different from the soft gelatin or powder-filled preparations, 0.87 +/- 0.14 and 0.86 +/- 0.074 versus 0.70 +/- 0.010 and 0.81 +/- 0.159 (microg/ml). Tmax however, was significantly shorter for the fast-melting and effervescent formulations compared with the soft gel and powder-filled forms, 1.3 +/- 0.348 and 2.0 +/- 0.552 versus 3.7 +/- 0.702 and 4.1 +/- 0.993 (h), respectively. The results of the second trial were similar to those of the powder-filled and soft gel formulations from the first study. The novel fast-melting and effervescent formulations provide a more rapid delivery of CoQ10 to the blood while exhibiting a similar AUC compared with current formulations. The potential clinical significance of this finding should be further evaluated.

[Regulation of the expression of coenzyme Q-synthesis complex during ageing].

PubMed

Campos-Silva, Carmen; Reyes-Torres, Iván; Rivera, Maximiliano; Meza-Torres, Catherine; Hernández-Camacho, Juan Diego; Rodríguez-Bies, Elisabet; Navas, Plácido; López-Lluch, Guillermo

Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing. The messenger RNA (mRNA) of different organs, such as brain, liver, kidney and skeletal muscle from young (8 months), mature (18 months), and old (24 months) mice was extracted by using Trizol and was then analysed by real time PCR (qPCR) using specific primers for all the known components of the coenzyme Q-synthesis complex (COQ genes). Liver showed the highest age-dependent changes in mRNA levels of the different components of Q-synthesis complex, affecting the extent of the variation as well as the significance of the change. In most of the cases, mRNA levels of the different components were higher in mature animals compared to young and old animals. When mRNAs of young and old animals were compared, only minor reductions of mRNA levels were found. Kidney showed a pattern similar to that found in liver as regards the changes in expression, although with lower increases in mature animals than those observed in the liver. Brain and skeletal muscle showed low variations, with muscle being the tissue with less changes, although a pattern similar to that found in liver and kidney was found, with slight increases in mature animals. The results of this study indicate that ageing is an important factor affecting COQ gene expression, but its effect depends on the organ, and that mature animals show higher levels of mRNA than young and old animals. Taken into consideration the importance of coenzyme Q in cell metabolism and ageing, a more detailed study is needed to understand the gene regulation of the coenzyme Q-synthesis mechanisms during ageing. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Novel Lipid-Free Nanoformulation for Improving Oral Bioavailability of Coenzyme Q10

PubMed Central

Zhou, Huafeng; Liu, Guoqing; Zhang, Jing; Sun, Ning; Duan, Mingxing; Yan, Zemin; Xia, Qiang

2014-01-01

To improve the bioavailability of orally administered lipophilic coenzyme Q10 (CoQ10), we formulated a novel lipid-free nano-CoQ10 system stabilized by various surfactants. Nano-CoQ10s, composed of 2.5% (w/w) CoQ10, 1.67% (w/w) surfactant, and 41.67% (w/w) glycerol, were prepared by hot high-pressure homogenization. The resulting formulations were characterized by particle size, zeta potential, differential scanning calorimetry, and cryogenic transmission electron microscopy. We found that the mean particle size of all nano-CoQ10s ranged from 66.3 ± 1.5 nm to 92.7 ± 1.5 nm and the zeta potential ranged from −12.8 ± 1.4 mV to −41.6 ± 1.4 mV. The CoQ10 in nano-CoQ10s likely existed in a supercooled state, and nano-CoQ10s stored in a brown sealed bottle were stable for 180 days at 25°C. The bioavailability of CoQ10 was evaluated following oral administration of CoQ10 formulations in Sprague-Dawley rats. Compared to the values observed following administration of CoQ10-Suspension, nano-CoQ10 modified with various surfactants significantly increased the maximum plasma concentration and the area under the plasma concentration-time curve. Thus, the lipid-free system of a nano-CoQ10 stabilized with a surfactant may be an effective vehicle for improving oral bioavailability of CoQ10. PMID:24995328

Metal plasmon-coupled fluorescence imaging and label free coenzyme detection in cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jian, E-mail: jian@cfs.bioment.umaryland.edu; Fu, Yi; Li, Ge

2012-08-31

Highlights: Black-Right-Pointing-Pointer Metal nanoparticle for fluorescence cell imaging. Black-Right-Pointing-Pointer Non-invasive emission detection of coenzyme in cell on time-resolved confocal microscope. Black-Right-Pointing-Pointer Near-field interaction of flavin adenine dinucleotide with silver substrate. Black-Right-Pointing-Pointer Isolation of emissions by coenzymes from cellular autofluorescence on fluorescence cell imaging. -- Abstract: Flavin adenine dinucleotide (FAD) is a key metabolite in cellular energy conversion. Flavin can also bind with some enzymes in the metabolic pathway and the binding sites may be changed due to the disease progression. Thus, there is interest on studying its expression level, distribution, and redox state within the cells. FAD is naturally fluorescent,more » but it has a modest extinction coefficient and quantum yield. Hence the intrinsic emission from FAD is generally too weak to be isolated distinctly from the cellular backgrounds in fluorescence cell imaging. In this article, the metal nanostructures on the glass coverslips were used as substrates to measure FAD in cells. Particulate silver films were fabricated with an optical resonance near the absorption and the emission wavelengths of FAD which can lead to efficient coupling interactions. As a result, the emission intensity and quantum yield by FAD were greatly increased and the lifetime was dramatically shortened resulting in less interference from the longer lived cellular background. This feature may overcome the technical limits that hinder the direct observation of intrinsically fluorescent coenzymes in the cells by fluorescence microscopy. Fluorescence cell imaging on the metallic particle substrates may provide a non-invasive strategy for collecting the information of coenzymes in cells.« less

Coenzyme Q10 Ameliorates Trimethyltin Chloride Neurotoxicity in Experimental Model of Injury in Dentate Gyrus of Hippocampus: A Histopathological and Behavioral Study

PubMed Central

Sakhaie, Mohammad Hassan; Soleimani, Mansoureh; Pirhajati, Vahid; Soleimani Asl, Sara; Madjd, Zahra; Mehdizadeh, Mehdi

2016-01-01

Background Coenzyme Q10 has antioxidative and free radical scavenging effects. CoQ10 supplementation is known to have neuroprotective effects in some neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. Objectives The aim of this study was to evaluate both histopathologic and behavioral whether Coenzyme Q10 is protective against trimethyltin chloride (TMT) induced hippocampal damage. Materials and Methods This was an experimental study. Thirty-six Balb/c mice were divided into four groups, as follows: 1) control group; 2) sham group of mice that received a 100 µL intraperitoneal injection (IP) of sesame oil; 3) TMT group of mice that received a single 2.5 mg/kg/day IP injection of TMT; and 4) TMT + CoQ10 group of mice that received a 10 mg/kg IP injection of CoQ10. Body weight and Morris water maze (MWM) responses were investigated. In addition, the dentate gyrus neurons of the hippocampus were evaluated histopathologically by light and electron microscopes. Results This study revealed that the body weight scale was found to be significantly higher in the CoQ10 group (21.39 ± 2.70), compared to the TMT group (19.39 ± 2.74) (P < 0.05). In the TMT group, the animals showed body a weight loss that was significantly lower than that of the control group (22.33 ± 3.06) (P < 0.05). Our results showed that CoQ10 provided protection against MWM deficits. Furthermore, TMT impaired the ability of mice to locate the hidden platform, compared to the control group (P < 0.05). Microscopic studies showed that TMT caused histopathological changes in the dentate gyrus and increased the number of necrotic neurons (476 ± 78.51), compared to the control group (208 ± 40.84) (P < 0.001). But, CoQ10 significantly attenuated (31 9 ± 60.08) the density of necrotic neurons compared to TMT (P < 0.05). Conclusions The results of the present study indicate that Coenzyme Q10 diminished neuronal necrosis and improved learning memory. Part of its beneficial effect is due to its potential to discount oxidative stress. PMID:27781114

The Impact of Coenzyme Q[subscript10] Supplement on the Indicators of Muscle Damage in Young Male Skiing Athletes

ERIC Educational Resources Information Center

Demirci, Nevzat

2015-01-01

This study was conducted in order to know the impact of coenzyme Q[subscript 10] (CoQ[subscript 10]) supplement on the muscle damage and total oxidant (TOS) enzyme levels of young skiing athletes during exercise. 15 male athletes were used for two weeks in the study. The athletes were divided into three groups: the control group and two subject…

Purification and properties of an O-acetyl-transferase from Escherichia coli that can O-acetylate polysialic acid sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higa, H.; Varki, A.

1986-05-01

Certain strains of bacteria synthesize an outer polysialic acid (K1) capsule. Some strains of K1/sup +/ E.coli are also capable of adding O-acetyl-esters to the exocyclic hydroxyl groups of the sialic acid residues. Both the capsule and the O-acetyl modification have been correlated with differences in antigenicity and pathogenicity. The authors have developed an assay for an O-acetyl-transferase in E.coli that transfers O-(/sup 3/H)acetyl groups from (/sup 3/H)acetyl-Coenzyme A to colominic acid (fragments of the polysialic acid capsule). Using this assay, the enzyme was solubilized, and purified approx. 600-fold using a single affinity chromatography step with Procion Red-A Agarose. Themore » enzyme also binds to Coenzyme A Sepharose, and can be eluted with high salt or Coenzyme A. The partially purified enzyme has a pH optimum of 7.0 - 7.5, is unaffected by divalent cations, is inhibited by high salt concentrations, is inhibited by Coenzyme A (50% inhibition at 100 ..mu..M), and shows an apparent Km for colominic acid of 3.7 mM (sialic acid concentration). This enzyme could be involved in the O-acetyl +/- form variation seen in some strains of K1/sup +/ E.coli.« less

Coenzyme Q{sub 10} and alpha-tocopherol protect against amitriptyline toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordero, Mario D.; Dpto. Citologia e Histologia Normal y Patologica, Facultad de Medicina. Universidad de Sevilla. 41009 Sevilla; Moreno-Fernandez, Ana Maria

Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q{sub 10} and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q{sub 10},more » decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q{sub 10} and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity.« less

Simultaneous determination of vitamin B12 and its derivatives using some of multivariate calibration 1 (MVC1) techniques

NASA Astrophysics Data System (ADS)

Samadi-Maybodi, Abdolraouf; Darzi, S. K. Hassani Nejad

2008-10-01

Resolution of binary mixtures of vitamin B12, methylcobalamin and B12 coenzyme with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable (PLS1), orthogonal signal correction/partial least squares (OSC/PLS), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-vis spectra. The UV-vis spectra of the vitamin B12, methylcobalamin and B12 coenzyme were recorded in the same spectral conditions. The method of central composite design was used in the ranges of 10-80 mg L -1 for vitamin B12 and methylcobalamin and 20-130 mg L -1 for B12 coenzyme. The models refinement procedure and validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 2.26 mg L -1 for vitamin B12 with PLS1, 1.33 mg L -1 for methylcobalamin with OSC/PLS and 3.24 mg L -1 for B12 coenzyme with HLA techniques. Figures of merit such as selectivity, sensitivity, analytical sensitivity and LOD were determined for three compounds. The procedure was successfully applied to simultaneous determination of three compounds in synthetic mixtures and in a pharmaceutical formulation.

Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice.

PubMed

Pegoraro, Natháli S; Barbieri, Allanna V; Camponogara, Camila; Mattiazzi, Juliane; Brum, Evelyne S; Marchiori, Marila C L; Oliveira, Sara M; Cruz, Letícia

2017-02-01

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Defined tetra-allelic gene disruption of the 4-coumarate:coenzyme A ligase 1 (Pv4CL1) gene by CRISPR/Cas9 in switchgrass results in lignin reduction and improved sugar release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jong -Jin; Yoo, Chang Geun; Flanagan, Amy

The development of genome editing technologies offers new prospects in improving bioenergy crops like switchgrass (Panicum virgatum). Switchgrass is an outcrossing species with an allotetraploid genome (2n = 4x = 36), a complexity which forms an impediment to generating homozygous knock-out plants. Lignin, a major component of the plant cell wall and a contributor to cellulosic feedstock’s recalcitrance to decomposition, stands as a barrier to efficient biofuel production by limiting enzyme access to cell wall polymers during the fermentation process.

Defined tetra-allelic gene disruption of the 4-coumarate:coenzyme A ligase 1 (Pv4CL1) gene by CRISPR/Cas9 in switchgrass results in lignin reduction and improved sugar release

DOE PAGES

Park, Jong -Jin; Yoo, Chang Geun; Flanagan, Amy; ...

2017-11-30

The development of genome editing technologies offers new prospects in improving bioenergy crops like switchgrass (Panicum virgatum). Switchgrass is an outcrossing species with an allotetraploid genome (2n = 4x = 36), a complexity which forms an impediment to generating homozygous knock-out plants. Lignin, a major component of the plant cell wall and a contributor to cellulosic feedstock’s recalcitrance to decomposition, stands as a barrier to efficient biofuel production by limiting enzyme access to cell wall polymers during the fermentation process.

Add-ons in IVF programme – Hype or Hope?

PubMed Central

Datta, AK; Campbell, S; Deval, B; Nargund, G

2015-01-01

A series of new technologies and adjuvant therapies have been advocated in order to improve the success of IVF treatment. Dehydro-epiandrostenedione, growth hormones, Coenzyme Q 10, calcium ionosphores, immune therapy, heparin, low-dose aspirin, and vasodilators are among commonly prescribed pharmacological adjuvants. New technologies that are proposed to improve IVF outcomes include advanced sperm selection procedures, time- lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury or embryo-glue. This review looked into current evidence to justify the use of these co-interventions and whether some of them can still be offered while awaiting more robust evidence to con rm or refute their role. PMID:27729969

Biochemistry of methyl-coenzyme M reductase: the nickel metalloenzyme that catalyzes the final step in synthesis and the first step in anaerobic oxidation of the greenhouse gas methane.

PubMed

Ragsdale, Stephen W

2014-01-01

Methane, the major component of natural gas, has been in use in human civilization since ancient times as a source of fuel and light. Methanogens are responsible for synthesis of most of the methane found on Earth. The enzyme responsible for catalyzing the chemical step of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole cofactor called coenzyme F430, which can traverse the Ni(I), (II), and (III) oxidation states. MCR and methanogens are also involved in anaerobic methane oxidation. This review describes structural, kinetic, and computational studies aimed at elucidating the mechanism of MCR. Such studies are expected to impact the many ramifications of methane in our society and environment, including energy production and greenhouse gas warming.

Physiological importance of the heterodisulfide of coenzyme M and 7-mercaptoheptanoylthreonine phosphate in the reduction of carbon dioxide to methane in Methanobacterium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bobik, T.A.; Wolfe, R.S.

1988-01-01

The heterodisulfide of the two coenzymes 2-mercaptoethanesulfonic acid (coenzyme M, HS-CoM) and N-(7-mercaptoheptanoyl)threonine O/sup 3/-phosphate (HS-HTP) increased the rate of CO/sub 2/ reduction to methane by cell extracts 42-fold. The stimulation resulted from activation of the initial step of methanogenesis, the production of formylmethanofuran from methanofuran and CO/sub 2/. These results establish a role for this heterodisulfide (CoM-S-S-HTP) in the reduction of CO/sub 2/ to formylmethanofuran. Evidence indicates that CoM-S-S-HTP is the labile intermediate that accounts for the coupling of the reduction of 2-(methylthio)ethanesulfonic acid by the methylreductase to formylmethanofuran biosynthesis, the RPG effect. The heterodisulfide was found to bemore » labile in cell extracts due to enzyme-catalyzed reduction and possibly thiol-disulfide exchange.« less

Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tavintharan, S.; Ong, C.N.; Jeyaseelan, K.

2007-09-01

Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ{sub 10}). In HepG2 cells, simvastatin decreased mitochondrial CoQ{sub 10} levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ{sub 10}, reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ{sub 10} deficiency plays an important role in statin-induced hepatopathy, and that CoQ{sub 10} supplementation protectsmore » HepG2 cells from this complication.« less

Novel HPLC-UV Method for Simultaneous Determination of Fat-soluble Vitamins and Coenzyme Q10 in Medicines and Supplements.

PubMed

Temova-Rakuša, Žane; Srečnik, Eva; Roškar, Robert

2017-09-01

A precise, accurate and rapid HPLC-UV method for simultaneous determination of fat-soluble vitamins (vitamin D3, E-acetate, K1, β-carotene, A-palmitate) and coenzyme Q10 was developed and validated according to ICH guidelines. Optimal chromatographic separation of the analytes in minimal analysis time (8 min) was achieved on a Luna C18 150 × 4.6 mm column using a mixture of acetonitrile, tetrahydrofuran and water (50:45:5, v/v/v). The described reversed phase HPLC method is the first published for quantification of these five fat-soluble vitamins and coenzyme Q10 within a single chromatographic run. The method was further applied for quantification of the analytes in selected liquid and solid dosage forms, registered as nutritional supplements and prescription medicines, which confirmed its suitability for routine analysis.

Overexpression of the Squalene Epoxidase Gene Alone and in Combination with the 3-Hydroxy-3-methylglutaryl Coenzyme A Gene Increases Ganoderic Acid Production in Ganoderma lingzhi.

PubMed

Zhang, De-Huai; Jiang, Lu-Xi; Li, Na; Yu, Xuya; Zhao, Peng; Li, Tao; Xu, Jun-Wei

2017-06-14

The squalene epoxidase (SE) gene from the biosynthetic pathway of ganoderic acid (GA) was cloned and overexpressed in Ganoderma lingzhi. The strain that overexpressed the SE produced approximately 2 times more GA molecules than the wild-type (WT) strain. Moreover, SE overexpression upregulated lanosterol synthase gene expression in the biosynthetic pathway. These results indicated that SE stimulates GA accumulation. Then, the SE and 3-hydroxy-3-methylglutaryl coenzyme A (HMGR) genes were simultaneously overexpressed in G. lingzhi. Compared with the individual overexpression of SE or HMGR, the combined overexpression of the two genes further enhanced individual GA production. The overexpressing strain produced maximum GA-T, GA-S, GA-Mk, and GA-Me contents of 90.4 ± 7.5, 35.9 ± 5.4, 6.2 ± 0.5, and 61.8 ± 5.8 μg/100 mg dry weight, respectively. These values were 5.9, 4.5, 2.4, and 5.8 times higher than those produced by the WT strain. This is the first example of the successful manipulation of multiple biosynthetic genes to improve GA content in G. lingzhi.

Phylogenetic and genomic analysis of Methanomassiliicoccales in wetlands and animal intestinal tracts reveals clade-specific habitat preferences.

PubMed

Söllinger, Andrea; Schwab, Clarissa; Weinmaier, Thomas; Loy, Alexander; Tveit, Alexander T; Schleper, Christa; Urich, Tim

2016-01-01

Methanogenic Thermoplasmata of the novel order Methanomassiliicoccales were recently discovered in human and animal gastro-intestinal tracts (GITs). However, their distribution in other methanogenic environments has not been addressed systematically. Here, we surveyed Methanomassiliicoccales presence in wetland soils, a globally important source of methane emissions to the atmosphere, and in the GITs of different animals by PCR targeting their 16S rRNA and methyl:coenzyme M reductase (α-subunit) genes. We detected Methanomassiliicoccales in all 16 peat soils investigated, indicating their wide distribution in these habitats. Additionally, we detected their genes in various animal faeces. Methanomassiliicoccales were subdivided in two broad phylogenetic clades designated 'environmental' and 'GIT' clades based on differential, although non-exclusive, habitat preferences of their members. A well-supported cluster within the environmental clade comprised more than 80% of all wetland 16S rRNA gene sequences. Metagenome assembly from bovine rumen fluid enrichments resulted in two almost complete genomes of both Methanomassiliicoccales clades. Comparative genomics revealed that members of the environmental clade contain larger genomes and a higher number of genes encoding anti-oxidative enzymes than animal GIT clade representatives. This study highlights the wide distribution of Methanomassiliicoccales in wetlands, which suggests that they contribute to methane emissions from these climate-relevant ecosystems. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.

PubMed

Alehagen, Urban; Aaseth, Jan; Alexander, Jan; Johansson, Peter

2018-01-01

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. Clinicaltrials.gov NCT01443780.

Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

PubMed

Alehagen, Urban; Johansson, Peter; Aaseth, Jan; Alexander, Jan; Wågsäter, Dick

2017-01-01

Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.

[Coenzyme Q10 enhances the expression of Bcl-2 and inhibits the expressions of Bax and GSK-3β in the hippocampus of rats exposed to ischemia/reperfusion injury].

PubMed

Tian, Shuang; Wang, Di; Li, Xiaodong; Tang, Jianjie; Han, Guang; Dai, Yongyi

2013-07-01

To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05). Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Biochemical and molecular characterization of the isocitrate dehydrogenase with dual coenzyme specificity from the obligate methylotroph Methylobacillus Flagellatus.

PubMed

Romkina, Anastasia Y; Kiriukhin, Michael Y

2017-01-01

The isocitrate dehydrogenase (MfIDH) with unique double coenzyme specificity from Methylobacillus flagellatus was purified and characterized, and its gene was cloned and overexpressed in E. coli as a fused protein. This enzyme is homodimeric,-with a subunit molecular mass of 45 kDa and a specific activity of 182 U mg -1 with NAD+ and 63 U mg -1 with NADP+. The MfIDH activity was dependent on divalent cations and Mn2+ enhanced the activity the most effectively. MfIDH exhibited a cofactor-dependent pH-activity profile. The optimum pH values were 8.5 (NAD+) and 6.0 (NADP+).The Km values for NAD+ and NADP+ were 113 μM and 184 μM respectively, while the Km values for DL-isocitrate were 9.0 μM (NAD+), 8.0 μM (NADP+). The MfIDH specificity (kcat/Km) was only 5-times higher for NAD+ than for NADP+. The purified MfIDH displayed maximal activity at 60°C. Heat-inactivation studies showed that the MfIDH was remarkably thermostable, retaining full activity at 50°C and losting ca. 50% of its activity after one hour of incubation at 75°C. The enzyme was insensitive to the presence of intermediate metabolites, with the exception of 2 mM ATP, which caused 50% inhibition of NADP+-linked activity. The indispensability of the N6 amino group of NAD(P)+ in its binding to MfIDH was demonstrated. MfIDH showed high sequence similarity with bacterial NAD(P)+-dependent type I isocitrate dehydrogenases (IDHs) rather than with eukaryotic NAD+-dependent IDHs. The unique double coenzyme specificity of MfIDH potentially resulted from the Lys340, Ile341 and Ala347 residues in the coenzyme-binding site of the enzyme. The discovery of a type I IDH with double coenzyme specificity elucidates the evolution of this subfamily IDHs and may provide fundamental information for engineering enzymes with desired properties.

Evidence for co-operativity in coenzyme binding to tetrameric Sulfolobus solfataricus alcohol dehydrogenase and its structural basis: fluorescence, kinetic and structural studies of the wild-type enzyme and non-co-operative N249Y mutant.

PubMed

Giordano, Antonietta; Febbraio, Ferdinando; Russo, Consiglia; Rossi, Mosè; Raia, Carlo A

2005-06-01

The interaction of coenzyme with thermostable homotetrameric NAD(H)-dependent alcohol dehydrogenase from the thermoacidophilic sulphur-dependent crenarchaeon Sulfolobus solfataricus (SsADH) and its N249Y (Asn-249-->Tyr) mutant was studied using the high fluorescence sensitivity of its tryptophan residues Trp-95 and Trp-117 to the binding of coenzyme moieties. Fluorescence quenching studies performed at 25 degrees C show that SsADH exhibits linearity in the NAD(H) binding [the Hill coefficient (h) approximately 1) at pH 9.8 and at moderate ionic strength, in addition to positive co-operativity (h=2.0-2.4) at pH 7.8 and 6.8, and at pH 9.8 in the presence of salt. Furthermore, NADH binding is positively co-operative below 20 degrees C (h approximately 3) and negatively co-operative at 40-50 degrees C (h approximately 0.7), as determined at moderate ionic strength and pH 9.8. Steady-state kinetic measurements show that SsADH displays standard Michaelis-Menten kinetics between 35 and 45 degrees C, but exhibits positive and negative co-operativity for NADH oxidation below (h=3.3 at 20 degrees C) and above (h=0.7 at 70-80 degrees C) this range of temperatures respectively. However, N249Y SsADH displays non-co-operative behaviour in coenzyme binding under the same experimental conditions used for the wild-type enzyme. In loop 270-275 of the coenzyme domain and segments at the interface of dimer A-B, analyses of the wild-type and mutant SsADH structures identified the structural elements involved in the intersubunit communication and suggested a possible structural basis for co-operativity. This is the first report of co-operativity in a tetrameric ADH and of temperature-induced co-operativity in a thermophilic enzyme.

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

PubMed Central

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

Structural Basis of the Induced-Fit Mechanism of 1,4-Dihydroxy-2-Naphthoyl Coenzyme A Synthase from the Crotonase Fold Superfamily

PubMed Central

Li, Jie; Li, Yan; Jiang, Ming; Zhou, Jiahai; Guo, Zhihong

2013-01-01

1, 4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase fold enzyme with an implicated role of conformational changes in catalysis. We have identified these conformational changes by determining the structures of its Escherichia coli and Synechocystis sp. PCC6803 orthologues in complex with a product analog. The structural changes include the folding of an active-site loop into a β-hairpin and significant reorientation of a helix at the carboxy terminus. Interestingly, a new interface is formed between the ordered loop and the reoriented helix, both of which also form additional interactions with the coenzyme A moiety of the ligand. Site-directed mutation of the amino acid residues involved in these ligand-induced interactions significantly diminishes the enzyme activity. These results suggest a catalytically essential induced-fit that is likely initiated by the enzyme-ligand interactions at the active site. PMID:23658663

The evolution of the genetic code: Impasses and challenges.

PubMed

Kun, Ádám; Radványi, Ádám

2018-02-01

The origin of the genetic code and translation is a "notoriously difficult problem". In this survey we present a list of questions that a full theory of the genetic code needs to answer. We assess the leading hypotheses according to these criteria. The stereochemical, the coding coenzyme handle, the coevolution, the four-column theory, the error minimization and the frozen accident hypotheses are discussed. The integration of these hypotheses can account for the origin of the genetic code. But experiments are badly needed. Thus we suggest a host of experiments that could (in)validate some of the models. We focus especially on the coding coenzyme handle hypothesis (CCH). The CCH suggests that amino acids attached to RNA handles enhanced catalytic activities of ribozymes. Alternatively, amino acids without handles or with a handle consisting of a single adenine, like in contemporary coenzymes could have been employed. All three scenarios can be tested in in vitro compartmentalized systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Probing Reversible Chemistry in Coenzyme B12-Dependent Ethanolamine Ammonia Lyase with Kinetic Isotope Effects

PubMed Central

Jones, Alex R; Rentergent, Julius; Scrutton, Nigel S; Hay, Sam

2015-01-01

Coenzyme B12-dependent enzymes such as ethanolamine ammonia lyase have remarkable catalytic power and some unique properties that enable detailed analysis of the reaction chemistry and associated dynamics. By selectively deuterating the substrate (ethanolamine) and/or the β-carbon of the 5′-deoxyadenosyl moiety of the intrinsic coenzyme B12, it was possible to experimentally probe both the forward and reverse hydrogen atom transfers between the 5′-deoxyadenosyl radical and substrate during single-turnover stopped-flow measurements. These data are interpreted within the context of a kinetic model where the 5′-deoxyadenosyl radical intermediate may be quasi-stable and rearrangement of the substrate radical is essentially irreversible. Global fitting of these data allows estimation of the intrinsic rate constants associated with CoC homolysis and initial H-abstraction steps. In contrast to previous stopped-flow studies, the apparent kinetic isotope effects are found to be relatively small. PMID:25950663

Balneotherapy and coenzyme Q10 in clinical and experimental medicine.

PubMed

Gvozdjakova, Anna; Kucharska, Jarmila; Sykora, L'ubomir; Singh, Ram B

2014-01-01

Balneotherapy or Spa therapy is used in neurological, cardiovascular, musculoskeletal, dermatological and gynecological diseases, in infertility as well as in metabolic disturbances. Beneficial effects of balneotherapy at the metabolic level is not fully understood. Authors have documented enhancement of antioxidants concentrations (coenzyme Q10- CoQ(10-OX) and alpha-tocopherol) of women with gynecological diseases by treatment with natural mineral water (Spa Lucky balneotherapy, Slovakia). In an experiment with rats, drinking of Spa Lucky mineral water decreased oxidative stress and enhanced concentrations of antioxidants CoQ(9-OX), CoQ(10-OX) in the myocardium, and alpha-tocopherol in uterus, ovaries and myocardium. Drinking of Spa Lucky water by rats stimulated myocardial mitochondrial respiration and energy production, and diminished skeletal muscle mitochondrial function. Simultaneous ingestion of coenzyme Q10 with drinking spa water returned mitochondrial parameters to the values of the control group. This pilot study helps explain the role of antioxidants, oxidative stress and mitochondrial energy production in beneficial effects of Spa Lucky balneotherapy.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

PubMed Central

Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

2013-01-01

AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

Combinatorial metabolic engineering of industrial Gluconobacter oxydans DSM2343 for boosting 5-keto-D-gluconic acid accumulation.

PubMed

Yuan, Jianfeng; Wu, Mianbin; Lin, Jianping; Yang, Lirong

2016-05-17

L-(+)-tartaric acid (L-TA) is an important organic acid, which is produced from the cream of tartar or stereospecific hydrolysis of the cis-epoxysuccinate. The former method is limited by the availability of raw material and the latter is dependent on the petrochemical material. Thus, new processes for the economical preparation of L-TA from carbohydrate or renewable resource would be much more attractive. Production of 5-keto-D-gluconate (5-KGA) from glucose by Gluconobacter oxydans is the first step to produce L-TA. The aim of this work is to enhance 5-KGA accumulation using combinatorial metabolic engineering strategies in G. oxydans. The sldAB gene, encoding sorbitol dehydrogenase, was overexpressed in an industrial strain G. oxydans ZJU2 under a carefully selected promoter, P0169. To enhance the efficiency of the oxidation by sldAB, the coenzyme pyrroloquinoline quinone (PQQ) and respiratory chain were engineered. Besides, the role in sldAB overexpression, coenzyme and respiratory chain engineering and their subsequent effects on 5-KGA production were investigated. An efficient, stable recombinant strain was constructed, whereas the 5-KGA production could be enhanced. By self-overexpressing the sldAB gene in G. oxydans ZJU2 under the constitutive promoter P0169, the resulting strain, G. oxydans ZJU3, produced 122.48 ± 0.41 g/L of 5-KGA. Furthermore, through the coenzyme and respiratory chain engineering, the titer and productivity of 5-KGA reached 144.52 ± 2.94 g/L and 2.26 g/(L · h), respectively, in a 15 L fermenter. It could be further improved the 5-KGA titer by 12.10 % through the fed-batch fermentation under the pH shift and dissolved oxygen tension (DOT) control condition, obtained 162 ± 2.12 g/L with the productivity of 2.53 g/(L · h) within 64 h. The 5-KGA production could be significantly enhanced with the combinatorial metabolic engineering strategy in Gluconobacter strain, including sldAB overexpression, coenzyme and respiratory chain engineering. Fed-batch fermentation could further enlarge the positive effect and increase the 5-KGA production. All of these demonstrated that the robust recombinant strain can efficiently produce 5-KGA in larger scale to fulfill the industrial production of L-TA from 5-KGA.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10.

PubMed

Somayajulu-Niţu, Mallika; Sandhu, Jagdeep K; Cohen, Jerome; Sikorska, Marianna; Sridhar, T S; Matei, Anca; Borowy-Borowski, Henryk; Pandey, Siyaram

2009-07-27

Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

PubMed Central

Johansson, Peter; Aaseth, Jan; Alexander, Jan; Wågsäter, Dick

2017-01-01

Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)–plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation. PMID:28448590

A mechanistic approach for modulation of chlorpyrifos-induced toxicity in human lymphocytes by melatonin, coenzyme Q10, and vinpocetine.

PubMed

Ghayomi, F; Navaei-Nigjeh, M; Baeeri, M; Rezvanfar, M A; Abdollahi, M

2016-08-01

Chlorpyrifos (CP) is an organophosphorus pesticide that induces oxidative stress through the production of free radicals and depletes intracellular antioxidant reserves. In this study, the efficacy of three antioxidants (melatonin, coenzyme Q10 (CoQ10), and vinpocetine) on alleviation of toxic effects of CP was evaluated. Cytotoxicity of CP, in the presence or absence of effective doses of melatonin, CoQ10, and vinpocetine, was determined in human peripheral blood lymphocytes after 72-h exposure. The levels of acetylcholinesterase (AChE) activity along with tumor necrosis factor α (TNF-α), as inflammatory index, were measured. Further, the viability and oxidative stress markers including cellular mitochondrial activity, cell death modes (apoptosis vs. necrosis), total antioxidant power (TAP), total thiol molecules (TTM), lipid peroxidation (LPO), and myeloperoxidase (MPO) activity were measured. CoQ10 and also the combination of the three antioxidants were the most notable in opposing toxicity of CP and led to increasing TAP and TTM; improvement of AChE activity; and lowering LPO, MPO, TNF-α, and apoptosis compared to CP alone. CP toxicity overwhelms the intracellular antioxidant defense mechanisms. Exogenous supplementation with antioxidants, such as the ones we have investigated, seems to be effective in the prevention of cytotoxicity of CP. © The Author(s) 2015.

Enhancement of solubility and dissolution of coenzyme Q10 using solid dispersion formulation.

PubMed

Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

2010-01-04

This study aimed to develop a stable solid dispersion of Coenzyme Q(10) (CoQ(10)) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ(10) having significantly enhanced solubility. Particularly, solid dispersion of CoQ(10) with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ(10) to the greatest extent. However, it exhibited poor stability and hence Aerosil 200 (colloidal silicon dioxide) was incorporated into the solid dispersion as an adsorbent to inhibit the recrystallization process. The solid dispersion of CoQ(10), poloxamer 407 and Aerosil 200 in the weight ratio of 1:5:6 exhibited improved stability with no significant change in solubility during the 1-month stability test. Moreover, the solid dispersion formulation containing Aerosil 200 significantly enhanced the extent of drug release (approx. 75% release) as well as the dissolution rate of CoQ(10). In conclusion, the present study has developed the stable solid dispersion formulation of CoQ(10) with poloxamer 407 and Aerosil 200 for the enhanced solubility and dissolution of CoQ(10), which could also offer some additional advantages including ease of preparation, good flowability and cost-effectiveness.

Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency.

PubMed

Montero, Raquel; Pineda, Mercé; Aracil, Asun; Vilaseca, Maria-Antonia; Briones, Paz; Sánchez-Alcázar, José-Antonio; Navas, Plácido; Artuch, Rafael

2007-01-01

Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting five phenotypes: a myopathic form, a severe infantile neurological syndrome associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure myopathic form. The third is the most common phenotype related with CoQ deficiency and it will be the focus of this review. This new syndrome presents muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as the main neurological signs. Biochemically, the hallmark of CoQ deficiency syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies associated with cerebellar ataxia, although recently a family has been reported with mutations at COQ2 gene who present a distinct phenotype. Patients with primary CoQ deficiency may benefit from CoQ supplementation, although the clinical response to this therapy varies even among patients with similar phenotypes. Some present an excellent response to CoQ while others show only a partial improvement of some symptoms and signs. CoQ deficiency is the mitochondrial encephalomyopathy with the best clinical response to CoQ supplementation, highlighting the importance of an early identification of this disorder.

A new double coupling system: synthesis of citronellyl acetate via transacetylation to citronellol from acetyl coenzyme A produced from glucose and free fatty acids.

PubMed

Oda, S; Ohta, H

2001-08-01

A double coupling system, which couples metabolism of glucose and transacetylation, is a unique procedure for the production of acetic esters. In the novel coupling system described in this article, acetyl coenzyme A (acetyl-CoA) was supplied via metabolism of both glucose and exogenous saturated fatty acids. While short and middle chain fatty acids having C4-8 were very biotoxic, myristic acid (C14) was effectively used as a source of acetyl-CoA.

Genetic engineering of Ganoderma lucidum for the efficient production of ganoderic acids.

PubMed

Xu, Jun-Wei; Zhong, Jian-Jiang

2015-01-01

Ganoderma lucidum is a well-known traditional medicinal mushroom that produces ganoderic acids with numerous interesting bioactivities. Genetic engineering is an efficient approach to improve ganoderic acid biosynthesis. However, reliable genetic transformation methods and appropriate genetic manipulation strategies remain underdeveloped and thus should be enhanced. We previously established a homologous genetic transformation method for G. lucidum; we also applied the established method to perform the deregulated overexpression of a homologous 3-hydroxy-3-methyl-glutaryl coenzyme A reductase gene in G. lucidum. Engineered strains accumulated more ganoderic acids than wild-type strains. In this report, the genetic transformation systems of G. lucidum are described; current trends are also presented to improve ganoderic acid production through the genetic manipulation of G. lucidum.

Evidence for co-operativity in coenzyme binding to tetrameric Sulfolobus solfataricus alcohol dehydrogenase and its structural basis: fluorescence, kinetic and structural studies of the wild-type enzyme and non-co-operative N249Y mutant

PubMed Central

2005-01-01

The interaction of coenzyme with thermostable homotetrameric NAD(H)-dependent alcohol dehydrogenase from the thermoacidophilic sulphur-dependent crenarchaeon Sulfolobus solfataricus (SsADH) and its N249Y (Asn-249→Tyr) mutant was studied using the high fluorescence sensitivity of its tryptophan residues Trp-95 and Trp-117 to the binding of coenzyme moieties. Fluorescence quenching studies performed at 25 °C show that SsADH exhibits linearity in the NAD(H) binding [the Hill coefficient (h)∼1) at pH 9.8 and at moderate ionic strength, in addition to positive co-operativity (h=2.0–2.4) at pH 7.8 and 6.8, and at pH 9.8 in the presence of salt. Furthermore, NADH binding is positively co-operative below 20 °C (h∼3) and negatively co-operative at 40–50 °C (h∼0.7), as determined at moderate ionic strength and pH 9.8. Steady-state kinetic measurements show that SsADH displays standard Michaelis–Menten kinetics between 35 and 45 °C, but exhibits positive and negative co-operativity for NADH oxidation below (h=3.3 at 20 °C) and above (h=0.7 at 70–80 °C) this range of temperatures respectively. However, N249Y SsADH displays non-co-operative behaviour in coenzyme binding under the same experimental conditions used for the wild-type enzyme. In loop 270–275 of the coenzyme domain and segments at the interface of dimer A–B, analyses of the wild-type and mutant SsADH structures identified the structural elements involved in the intersubunit communication and suggested a possible structural basis for co-operativity. This is the first report of co-operativity in a tetrameric ADH and of temperature-induced co-operativity in a thermophilic enzyme. PMID:15651978

N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation

PubMed Central

Moffett, John R.; Arun, Peethambaran; Ariyannur, Prasanth S.; Namboodiri, Aryan M. A.

2013-01-01

N-Acetylaspartate (NAA) is employed as a non-invasive marker for neuronal health using proton magnetic resonance spectroscopy (MRS). This utility is afforded by the fact that NAA is one of the most concentrated brain metabolites and that it produces the largest peak in MRS scans of the healthy human brain. NAA levels in the brain are reduced proportionately to the degree of tissue damage after traumatic brain injury (TBI) and the reductions parallel the reductions in ATP levels. Because NAA is the most concentrated acetylated metabolite in the brain, we have hypothesized that NAA acts in part as an extensive reservoir of acetate for acetyl coenzyme A synthesis. Therefore, the loss of NAA after TBI impairs acetyl coenzyme A dependent functions including energy derivation, lipid synthesis, and protein acetylation reactions in distinct ways in different cell populations. The enzymes involved in synthesizing and metabolizing NAA are predominantly expressed in neurons and oligodendrocytes, respectively, and therefore some proportion of NAA must be transferred between cell types before the acetate can be liberated, converted to acetyl coenzyme A and utilized. Studies have indicated that glucose metabolism in neurons is reduced, but that acetate metabolism in astrocytes is increased following TBI, possibly reflecting an increased role for non-glucose energy sources in response to injury. NAA can provide additional acetate for intercellular metabolite trafficking to maintain acetyl CoA levels after injury. Here we explore changes in NAA, acetate, and acetyl coenzyme A metabolism in response to brain injury. PMID:24421768

Nuclear-cytoplasmic localization of acetyl coenzyme A synthetase-1 in the rat brain

PubMed Central

Ariyannur, Prasanth S.; Moffett, John R.; Madhavarao, Chikkathur N; Arun, Peethambaran; Vishnu, Nisha; Jacobowitz, David M.; Hallows, William C.; Denu, John M.; Namboodiri, Aryan M.A.

2011-01-01

Acetyl coenzyme A synthetase 1 (AceCS1) catalyzes the synthesis of acetyl coenzyme A from acetate and coenzyme A, and is thought to play diverse roles ranging from fatty acid synthesis to gene regulation. Using an affinity purified antibody generated against an 18-mer peptide sequence of AceCS1, and a polyclonal antibody directed against recombinant AceCS1 protein, we examined the expression of AceCS1 in the rat brain. AceCS1 immunoreactivity in the adult rat brain was present predominantly in cell nuclei, with only light to moderate cytoplasmic staining in some neurons, axons and oligodendrocytes. Some non-neuronal cell nuclei were very strongly immunoreactive, including those of some oligodendrocytes, whereas neuronal nuclei ranged from unstained to moderately stained. Both antibodies stained some neuronal cell bodies and axons, especially in the hindbrain. AceCS1 immunoreactivity was stronger and more widespread in the brains of 18 day old rats than in adults, with increased expression in oligodendrocytes and neurons, including cortical pyramidal cells. Expression of AceCS1 was substantially upregulated in neurons throughout the brain after controlled cortical impact injury. The strong AceCS1 expression observed in the nuclei of CNS cells during brain development and after injury is consistent with a role in nuclear histone acetylation and therefore the regulation of chromatin structure and gene expression. The cytoplasmic staining observed in some oligodendrocytes, especially during postnatal brain development, suggests an additional role in CNS lipid synthesis and myelination. Neuronal and axonal localization implicates AceCS1 in cytoplasmic acetylation reactions in some neurons. PMID:20533355

A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome.

PubMed

Ngu, Lock Hock; Nijtmans, Leo G; Distelmaier, Felix; Venselaar, Hanka; van Emst-de Vries, Sjenet E; van den Brand, Mariël A M; Stoltenborg, Berendien J M; Wintjes, Liesbeth T; Willems, Peter H; van den Heuvel, Lambertus P; Smeitink, Jan A; Rodenburg, Richard J T

2012-02-01

In this study, we investigated the pathogenicity of a homozygous Asp446Asn mutation in the NDUFS2 gene of a patient with a mitochondrial respiratory chain complex I deficiency. The clinical, biochemical, and genetic features of the NDUFS2 patient were compared with those of 4 patients with previously identified NDUFS2 mutations. All 5 patients presented with Leigh syndrome. In addition, 3 out of 5 showed hypertrophic cardiomyopathy. Complex I amounts in the patient carrying the Asp446Asn mutation were normal, while the complex I activity was strongly reduced, showing that the NDUFS2 mutation affects complex I enzymatic function. By contrast, the 4 other NDUFS2 patients showed both a reduced amount and activity of complex I. The enzymatic defect in fibroblasts of the patient carrying the Asp446Asn mutation was rescued by transduction of wild type NDUFS2. A 3-D model of the catalytic core of complex I showed that the mutated amino acid residue resides near the coenzyme Q binding pocket. However, the K(M) of complex I for coenzyme Q analogs of the Asp446Asn mutated complex I was similar to the K(M) observed in other complex I defects and in controls. We propose that the mutation interferes with the reduction of coenzyme Q or with the coupling of coenzyme Q reduction with the conformational changes involved in proton pumping of complex I. Copyright © 2011 Elsevier B.V. All rights reserved.

Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse

PubMed Central

Porter, Richard K.; Katz, Lisa M.; Hill, Emmeline W.

2017-01-01

Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred horses. Skeletal muscle fibre type proportions were significantly (p < 0.01) different among the three MSTN genotypes and mitochondrial content was significantly (p < 0.01) lower in the combined presence of the C-allele of SNP g.66493737C>T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN horses. PMID:29190290

Identification of a magnesium-dependent NAD(P)(H)-binding domain in the nicotinoprotein methanol dehydrogenase from Bacillus methanolicus.

PubMed

Hektor, Harm J; Kloosterman, Harm; Dijkhuizen, Lubbert

2002-12-06

The Bacillus methanolicus methanol dehydrogenase (MDH) is a decameric nicotinoprotein alcohol dehydrogenase (family III) with one Zn(2+) ion, one or two Mg(2+) ions, and a tightly bound cofactor NAD(H) per subunit. The Mg(2+) ions are essential for binding of cofactor NAD(H) in MDH. A B. methanolicus activator protein strongly stimulates the relatively low coenzyme NAD(+)-dependent MDH activity, involving hydrolytic removal of the NMN(H) moiety of cofactor NAD(H) (Kloosterman, H., Vrijbloed, J. W., and Dijkhuizen, L. (2002) J. Biol. Chem. 277, 34785-34792). Members of family III of NAD(P)-dependent alcohol dehydrogenases contain three unique, conserved sequence motifs (domains A, B, and C). Domain C is thought to be involved in metal binding, whereas the functions of domains A and B are still unknown. This paper provides evidence that domain A constitutes (part of) a new magnesium-dependent NAD(P)(H)-binding domain. Site-directed mutants D100N and K103R lacked (most of the) bound cofactor NAD(H) and had lost all coenzyme NAD(+)-dependent MDH activity. Also mutants G95A and S97G were both impaired in cofactor NAD(H) binding but retained coenzyme NAD(+)-dependent MDH activity. Mutant G95A displayed a rather low MDH activity, whereas mutant S97G was insensitive to activator protein but displayed "fully activated" MDH reaction rates. The various roles of these amino acid residues in coenzyme and/or cofactor NAD(H) binding in MDH are discussed.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

PubMed Central

Somayajulu-Niţu, Mallika; Sandhu, Jagdeep K; Cohen, Jerome; Sikorska, Marianna; Sridhar, TS; Matei, Anca; Borowy-Borowski, Henryk; Pandey, Siyaram

2009-01-01

Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses. PMID:19635141

The effect of coenzyme Q10 in statin myopathy.

PubMed

Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

2012-01-01

Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001). After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

PubMed

Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V

2007-04-01

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

DOE PAGES

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne; ...

2014-12-11

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

A new role for coenzyme F420 in aflatoxin reduction by soil mycobacteria.

PubMed

Graham, David E

2010-11-01

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxal 5'-phosphate synthases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced, low-potential deazaflavin to the electron-deficient ring systems of their substrates. © 2010 Blackwell Publishing Ltd.

MicroCommentary: A New Role for Coenzyme F420 in Aflatoxin Reduction by Soil Mycobacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, David E

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxalamine 5 -phosphate oxidases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced deazaflavin to the electron-deficient ring systems of their substrates.

Benzoate Mediates Repression of C4-Dicarboxylate Utilization in “Aromatoleum aromaticum” EbN1

PubMed Central

Trautwein, Kathleen; Grundmann, Olav; Wöhlbrand, Lars; Eberlein, Christian; Boll, Matthias

2012-01-01

Diauxic growth was observed in anaerobic C4-dicarboxylate-adapted cells of “Aromatoleum aromaticum” EbN1 due to preferred benzoate utilization from a substrate mixture of a C4-dicarboxylate (succinate, fumarate, or malate) and benzoate. Differential protein profiles (two-dimensional difference gel electrophoresis [2D DIGE]) revealed dynamic changes in abundance for proteins involved in anaerobic benzoate catabolism and C4-dicarboxylate uptake. In the first active growth phase, benzoate utilization was paralleled by maximal abundance of proteins involved in anaerobic benzoate degradation (e.g., benzoyl-coenzyme A [CoA] reductase) and minimal abundance of DctP (EbA4158), the periplasmic binding protein of a predicted C4-dicarboxylate tripartite ATP-independent periplasmic (TRAP) transporter (DctPQM). The opposite was observed during subsequent succinate utilization in the second active growth phase. The increased dctP (respectively, dctPQM) transcript and DctP protein abundance following benzoate depletion suggests that repression of C4-dicarboxylate uptake seems to be a main determinant for the observed diauxie. PMID:22081395

Lysophosphatidic Acid Acyltransferase from Coconut Endosperm Mediates the Insertion of Laurate at the sn-2 Position of Triacylglycerols in Lauric Rapeseed Oil and Can Increase Total Laurate Levels

PubMed Central

Knutzon, Deborah S.; Hayes, Thomas R.; Wyrick, Annette; Xiong, Hui; Maelor Davies, H.; Voelker, Toni A.

1999-01-01

Expression of a California bay laurel (Umbellularia californica) 12:0-acyl-carrier protein thioesterase, bay thioesterase (BTE), in developing seeds of oilseed rape (Brassica napus) led to the production of oils containing up to 50% laurate. In these BTE oils, laurate is found almost exclusively at the sn-1 and sn-3 positions of the triacylglycerols (T.A. Voelker, T.R. Hayes, A.C. Cranmer, H.M. Davies [1996] Plant J 9: 229–241). Coexpression of a coconut (Cocos nucifera) 12:0-coenzyme A-preferring lysophosphatitic acid acyltransferase (D.S. Knutzon, K.D. Lardizabal, J.S. Nelsen, J.L. Bleibaum, H.M. Davies, J.G. Metz [1995] Plant Physiol 109: 999–1006) in BTE oilseed rape seeds facilitates efficient laurate deposition at the sn-2 position, resulting in the acccumulation of trilaurin. The introduction of the coconut protein into BTE oilseed rape lines with laurate above 50 mol % further increases total laurate levels. PMID:10398708

Crystal structure of substrate free form of glycerol dehydratase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Der-Ing; Dotson, Garry; Turner, Jr., Ivan

2010-03-08

Glycerol dehydratase (GDH) and diol dehydratase (DDH) are highly homologous isofunctional enzymes that catalyze the elimination of water from glycerol and 1,2-propanediol (1,2-PD) to the corresponding aldehyde via a coenzyme B{sub 12}-dependent radical mechanism. The crystal structure of substrate free form of GDH in complex with cobalamin and K{sup +} has been determined at 2.5 {angstrom} resolution. Its overall fold and the subunit assembly closely resemble those of DDH. Comparison of this structure and the DDH structure, available only in substrate bound form, shows the expected change of the coordination of the essential K{sup +} from hexacoordinate to heptacoordinate withmore » the displacement of a single coordinated water by the substrate diol. In addition, there appears to be an increase in the rigidity of the K{sup +} coordination (as measured by lower B values) upon the binding of the substrate. Structural analysis of the locations of conserved residues among various GDH and DDH sequences has aided in identification of residues potentially important for substrate preference or specificity of protein-protein interactions.« less

The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.

PubMed

Suzuki, S; Hinokio, Y; Ohtomo, M; Hirai, M; Hirai, A; Chiba, M; Kasuga, S; Satoh, Y; Akai, H; Toyota, T

1998-05-01

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity.

PubMed

Aksentijević, Dunja; McAndrew, Debra J; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D; Neubauer, Stefan; Lygate, Craig A

2014-10-01

Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. MCD knockout mice ((-/-)) exhibited non-Mendelian genotype ratios (31% fewer MCD(-/-)) with deaths clustered around weaning. Immediately prior to weaning (18days) MCD(-/-) mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD(-/-) plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD(-/-) hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD(-/-) converged with age, suggesting that, in surviving MCD(-/-) mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD(-/-) metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. MCD(-/-) mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. Copyright © 2014. Published by Elsevier Ltd.

Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity

PubMed Central

Aksentijević, Dunja; McAndrew, Debra J.; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D.; Neubauer, Stefan; Lygate, Craig A.

2014-01-01

Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~ 40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. Aim To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. Methods and results MCD knockout mice (−/−) exhibited non-Mendelian genotype ratios (31% fewer MCD−/−) with deaths clustered around weaning. Immediately prior to weaning (18 days) MCD−/− mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD−/− plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD−/− hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD−/− converged with age, suggesting that, in surviving MCD−/− mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD−/− metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. Conclusions MCD−/− mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. PMID:25066696

Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement

PubMed Central

Cordero, Mario D.; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

2012-01-01

Background Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q10 (CoQ10) supplementation on biochemical markers and clinical improvement were also evaluated. Methods We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ10, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. Results We found decreased CoQ10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ10 or catalase levels in BMCs and headache parameters were observed (r = −0.59, P<0.05; r = −0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001). Discussion The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM. PMID:22532869

Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.

PubMed

Cordero, Mario D; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

2012-01-01

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q(10) (CoQ(10)) supplementation on biochemical markers and clinical improvement were also evaluated. We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ(10), catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. We found decreased CoQ(10), catalase and ATP levels in BMCs from FM patients as compared to normal control (P < 0.05 and P < 0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P < 0.001). Significant negative correlations between CoQ(10) or catalase levels in BMCs and headache parameters were observed (r  = -0.59, P < 0.05; r  =  -0.68, P < 0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ(10) supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P < 0.001). The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.

Epoxyalkane:Coenzyme M Transferase Gene Diversity and Distribution in Groundwater Samples from Chlorinated-Ethene-Contaminated Sites

PubMed Central

Liu, Xikun

2016-01-01

ABSTRACT Epoxyalkane:coenzyme M transferase (EaCoMT) plays a critical role in the aerobic biodegradation and assimilation of alkenes, including ethene, propene, and the toxic chloroethene vinyl chloride (VC). To improve our understanding of the diversity and distribution of EaCoMT genes in the environment, novel EaCoMT-specific terminal-restriction fragment length polymorphism (T-RFLP) and nested-PCR methods were developed and applied to groundwater samples from six different contaminated sites. T-RFLP analysis revealed 192 different EaCoMT T-RFs. Using clone libraries, we retrieved 139 EaCoMT gene sequences from these samples. Phylogenetic analysis revealed that a majority of the sequences (78.4%) grouped with EaCoMT genes found in VC- and ethene-assimilating Mycobacterium strains and Nocardioides sp. strain JS614. The four most-abundant T-RFs were also matched with EaCoMT clone sequences related to Mycobacterium and Nocardioides strains. The remaining EaCoMT sequences clustered within two emergent EaCoMT gene subgroups represented by sequences found in propene-assimilating Gordonia rubripertincta strain B-276 and Xanthobacter autotrophicus strain Py2. EaCoMT gene abundance was positively correlated with VC and ethene concentrations at the sites studied. IMPORTANCE The EaCoMT gene plays a critical role in assimilation of short-chain alkenes, such as ethene, VC, and propene. An improved understanding of EaCoMT gene diversity and distribution is significant to the field of bioremediation in several ways. The expansion of the EaCoMT gene database and identification of incorrectly annotated EaCoMT genes currently in the database will facilitate improved design of environmental molecular diagnostic tools and high-throughput sequencing approaches for future bioremediation studies. Our results further suggest that potentially significant aerobic VC degraders in the environment are not well represented in pure culture. Future research should aim to isolate and characterize aerobic VC-degrading bacteria from these underrepresented groups. PMID:27016563

Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials.

PubMed

Bhatt, Kunal N; Butler, Javed

2018-06-01

Several novel therapeutics being tested in patients with heart failure are based on myocardial energetics. This review will provide a summary of the recent trials in this area, including therapeutic options targeting various aspects of cellular and mitochondrial metabolism. Agents that improve the energetic balance in myocardial cells have the potential to improve clinical heart failure status. The most promising therapies currently under investigation in this arena include (1) elamipretide, a cardiolipin stabilizer; (2) repletion of iron deficiency with intravenous ferrous carboxymaltose; (3) coenzyme Q10; and (4) the partial adenosine receptor antagonists capadenoson and neladenosone. Myocardial energetics-based therapeutics are groundbreaking in that they utilize novel mechanisms of action to improve heart failure symptoms, without causing the adverse neurohormonal side effects associated with current guideline-based therapies. The drugs appear likely to be added to the heart failure therapy armamentarium as adjuncts to current regimens in the near future.

Genetic engineering of Ganoderma lucidum for the efficient production of ganoderic acids

PubMed Central

Xu, Jun-Wei; Zhong, Jian-Jiang

2015-01-01

Ganoderma lucidum is a well-known traditional medicinal mushroom that produces ganoderic acids with numerous interesting bioactivities. Genetic engineering is an efficient approach to improve ganoderic acid biosynthesis. However, reliable genetic transformation methods and appropriate genetic manipulation strategies remain underdeveloped and thus should be enhanced. We previously established a homologous genetic transformation method for G. lucidum; we also applied the established method to perform the deregulated overexpression of a homologous 3-hydroxy-3-methyl-glutaryl coenzyme A reductase gene in G. lucidum. Engineered strains accumulated more ganoderic acids than wild-type strains. In this report, the genetic transformation systems of G. lucidum are described; current trends are also presented to improve ganoderic acid production through the genetic manipulation of G. lucidum. PMID:26588475

Methyl-coenzyme M reductase from methanogenic archaea: isotope effects on label exchange and ethane formation with the homologous substrate ethyl-coenzyme M.

PubMed

Scheller, Silvan; Goenrich, Meike; Thauer, Rudolf K; Jaun, Bernhard

2013-10-09

Ethyl-coenzyme M (CH3CH2-S-CH2CH2-SO3(-), Et-S-CoM) serves as a homologous substrate for the enzyme methyl-coenzyme M reductase (MCR) resulting in the product ethane instead of methane. The catalytic reaction proceeds via an intermediate that already contains all six C-H bonds of the product. Because product release occurs after a second, rate-limiting step, many cycles of intermediate formation and reconversion to substrate occur before a substantial amount of ethane is released. In deuterated buffer, the intermediate becomes labeled, and C-H activation in the back reaction rapidly leads to labeled Et-S-CoM, which enables intermediate formation to be detected. Here, we present a comprehensive analysis of this pre-equilibrium. (2)H- and (13)C-labeled isotopologues of Et-S-CoM were used as the substrates, and the time course of each isotopologue was followed by NMR spectroscopy. A kinetic simulation including kinetic isotope effects allowed determination of the primary and α- and β-secondary isotope effects for intermediate formation and for the C-H/C-D bond activation in the ethane-containing intermediate. The values obtained are in accordance with those found for the native substrate Me-S-CoM (see preceding publication, Scheller, S.; Goenrich, M.; Thauer, R. K.; Jaun, B. J. Am. Chem. Soc. 2013, 135, DOI: 10.1021/ja406485z) and thus imply the same catalytic mechanism for both substrates. The experiment by Floss and co-workers, demonstrating a net inversion of configuration to chiral ethane with CH3CDT-S-CoM as the substrate, is compatible with the observed rapid isotope exchange if the isotope effects measured here are taken into account.

Preferred skin color enhancement for photographic color reproduction

NASA Astrophysics Data System (ADS)

Zeng, Huanzhao; Luo, Ronnier

2011-01-01

Skin tones are the most important colors among the memory color category. Reproducing skin colors pleasingly is an important factor in photographic color reproduction. Moving skin colors toward their preferred skin color center improves the color preference of skin color reproduction. Several methods to morph skin colors to a smaller preferred skin color region has been reported in the past. In this paper, a new approach is proposed to further improve the result of skin color enhancement. An ellipsoid skin color model is applied to compute skin color probabilities for skin color detection and to determine a weight for skin color adjustment. Preferred skin color centers determined through psychophysical experiments were applied for color adjustment. Preferred skin color centers for dark, medium, and light skin colors are applied to adjust skin colors differently. Skin colors are morphed toward their preferred color centers. A special processing is applied to avoid contrast loss in highlight. A 3-D interpolation method is applied to fix a potential contouring problem and to improve color processing efficiency. An psychophysical experiment validates that the method of preferred skin color enhancement effectively identifies skin colors, improves the skin color preference, and does not objectionably affect preferred skin colors in original images.

Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage

PubMed Central

Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y.; Afrin, Sadia; Reboredo-Rodriguez, Patricia; Cianciosi, Danila; Mezzetti, Bruno; Quiles, Josè L.; Bompadre, Stefano; Battino, Maurizio; Giampieri, Francesca

2017-01-01

Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 μg/mL)-based formulations supplemented with Coenzyme Q10 (100 μg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p < 0.05) photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents. PMID:28613256

Improving coenzyme Q8 production in Escherichia coli employing multiple strategies.

PubMed

Xu, Wen; Yang, Shuiyun; Zhao, Junchao; Su, Tingting; Zhao, Liangrui; Liu, Jiankang

2014-08-01

Coenzyme Q (CoQ) is a medically valuable compound and a high yielding strain for CoQ will have several benefits for the industrial production of CoQ. To increase the CoQ(8) content of E. coli, we blocked the pathway for the synthesis of menaquinone by deleting the menA gene. The blocking of menaquinone pathway increased the CoQ(8) content by 81 % in E. coli (ΔmenA). To study the CoQ producing potential of E. coli, we employed previous known increasing strategies for systematic metabolic engineering. These include the supplementation with substrate precursors and the co-expression of rate-limiting genes. The co-expression of dxs-ubiA and the supplementation with substrate precursors such as pyruvate (PYR) and parahydroxybenzoic acid (pHBA) increased the content of CoQ(8) in E. coli (ΔmenA) by 125 and 59 %, respectively. Moreover, a 180 % increase in the CoQ(8) content in E. coli (ΔmenA) was realized by the combination of the co-expression of dxs-ubiA and the supplementation with PYR and pHBA. All in all, CoQ(8) content in E. coli increased 4.06 times by blocking the menaquinone pathway, dxs-ubiA co-expression and the addition of sodium pyruvate and parahydroxybenzoic acid to the medium. Results suggested a synergistic effect among different metabolic engineering strategies.

Protective effects of coenzyme q(10) on decreased oxidative stress resistance induced by simvastatin.

PubMed

Kettawan, Aikkarach; Takahashi, Takayuki; Kongkachuichai, Ratchanee; Charoenkiatkul, Somsri; Kishi, Takeo; Okamoto, Tadashi

2007-05-01

The effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), on oxidative stress resistance and the protective effects of coenzyme Q (CoQ) were investigated. When simvastatin was administered orally to mice, the levels of oxidized and reduced CoQ(9) and CoQ(10) in serum, liver, and heart, decreased significantly when compared to those of control. The levels of thiobarbituric acid reactive substances induced by Fe(2+)-ascorbate in liver and heart mitochondria also increased significantly with simvastatin. Furthermore, cultured cardiac myocytes treated with simvastatin exhibited less resistance to oxidative stress, decreased time to the cessation of spontaneous beating in response to H(2)O(2) addition, and decreased responsiveness to electrical field stimulation. These results suggested that oral administration of simvastatin suppresses the biosynthesis of CoQ, which shares the same biosynthesis pathway as cholesterol up to farnesyl pyrophosphate, thus compromising the physiological function of reduced CoQ, which possesses antioxidant activity. However, these undesirable effects induced by simvastatin were alleviated by coadministering CoQ(10) with simvastatin to mice. Simvastatin also reduced the activity of NADPH-CoQ reductase, a biological enzyme that converts oxidized CoQ to the corresponding reduced CoQ, while CoQ(10) administration improved it. These findings may also support the efficacy of coadministering CoQ(10) with statins.

Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency.

PubMed

Salviati, Leonardo; Trevisson, Eva; Rodriguez Hernandez, Maria Angeles; Casarin, Alberto; Pertegato, Vanessa; Doimo, Mara; Cassina, Matteo; Agosto, Caterina; Desbats, Maria Andrea; Sartori, Geppo; Sacconi, Sabrina; Memo, Luigi; Zuffardi, Orsetta; Artuch, Rafael; Quinzii, Catarina; Dimauro, Salvatore; Hirano, Michio; Santos-Ocaña, Carlos; Navas, Plácido

2012-03-01

COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency. A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. The study found reduced COQ4 expression (48% of controls), CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. Mutations of COQ4 should be searched for in patients with CoQ(10) deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ(10) deficiency, as they could benefit from supplementation.

Coenzyme Q10 Supplementation in Aging and Disease

PubMed Central

Hernández-Camacho, Juan D.; Bernier, Michel; López-Lluch, Guillermo; Navas, Plácido

2018-01-01

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have collected published results from clinical trials based on CoQ10 supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility. PMID:29459830

Flavoenzymes: Versatile Catalysts in Biosynthetic Pathways

PubMed Central

Walsh, Christopher T.; Wencewicz, Timothy A.

2012-01-01

Riboflavin-based coenzymes, tightly bound to enzymes catalyzing substrate oxidations and reductions, enable an enormous range of chemical transformations in biosynthetic pathways. Flavoenzymes catalyze substrate oxidations involving amine and alcohol oxidations and desaturations to olefins, the latter setting up Diels-Alder cyclizations in lovastatin and solanapyrone biosyntheses. Both C4a and N5 of the flavin coenzymes are sites for covalent adduct formation. For example, the reactivity of dihydroflavins with molecular oxygen leads to flavin-4a-OOH adducts which then carry out a diverse range of oxygen transfers, including Baeyer-Villiger type ring expansions, olefin epoxidations, halogenations via transient HOCl generation, and an oxidative Favorskii rerrangement during enterocin assembly. PMID:23051833

Flavoenzymes: versatile catalysts in biosynthetic pathways.

PubMed

Walsh, Christopher T; Wencewicz, Timothy A

2013-01-01

Riboflavin-based coenzymes, tightly bound to enzymes catalyzing substrate oxidations and reductions, enable an enormous range of chemical transformations in biosynthetic pathways. Flavoenzymes catalyze substrate oxidations involving amine and alcohol oxidations and desaturations to olefins, the latter setting up Diels-Alder cyclizations in lovastatin and solanapyrone biosyntheses. Both C(4a) and N(5) of the flavin coenzymes are sites for covalent adduct formation. For example, the reactivity of dihydroflavins with molecular oxygen leads to flavin-4a-OOH adducts which then carry out a diverse range of oxygen transfers, including Baeyer-Villiger type ring expansions, olefin epoxidations, halogenations via transient HOCl generation, and an oxidative Favorskii rerrangement during enterocin assembly.

Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds

NASA Astrophysics Data System (ADS)

Weckbecker, Andrea; Gröger, Harald; Hummel, Werner

Dehydrogenases which depend on nicotinamide coenzymes are of increasing interest for the preparation of chiral compounds, either by reduction of a prochiral precursor or by oxidative resolution of their racemate. The regeneration of oxidized and reduced nicotinamide cofactors is a very crucial step because the use of these cofactors in stoichiometric amounts is too expensive for application. There are several possibilities to regenerate nicotinamide cofactors: established methods such as formate/formate dehydrogenase (FDH) for the regeneration of NADH, recently developed electrochemical methods based on new mediator structures, or the application of gene cloning methods for the construction of "designed" cells by heterologous expression of appropriate genes.

Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency.

PubMed

Di Giovanni, S; Mirabella, M; Spinazzola, A; Crociani, P; Silvestri, G; Broccolini, A; Tonali, P; Di Mauro, S; Servidei, S

2001-08-14

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

PubMed

Hiramine, Yasushi; Tanabe, Toshizumi

2011-06-01

Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

The role of coenzyme Q-10 in aging: a follow-up study on life-long oral supplementation Q-10 in rats.

PubMed

Lönnrot, K; Metsä-Ketelä, T; Alho, H

1995-01-01

The essential role of coenzyme Q--ubiquinone--in biological energy transduction is well established. Reduced Q--ubiquinol--has also been shown to act as an antioxidant and to decrease the action of free radicals, which in turn could cause damage to structural lipids or proteins. The accumulation of lipopigments during aging in several peripheral organs and in the nervous system is considered to be related to the peroxidation of unsaturated fatty acids. An age-related decline of Q-10 has been suggested to occur in man and rats. In this study we followed the effects of life-long oral supplementation of coenzyme Q-10 on the development and life-span and pigment accumulation in peripheral tissues and the nervous system of laboratory rats. The Q-10 supplemented group showed a significant increase in Q-10 in plasma and liver, while it was unchanged in other tissues. There was no significant difference between the two groups in the development and mortality of the animals. No differences were observed in lipopigment accumulation. Our results indicate that in rats, life-long supplementation of Q-10 has no beneficial effects on life-span or pigment accumulation.

Methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction.

PubMed

Wagner, Tristan; Koch, Jürgen; Ermler, Ulrich; Shima, Seigo

2017-08-18

In methanogenic archaea, the carbon dioxide (CO 2 ) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B. Here, we present the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15-angstrom resolution. HdrB contains two noncubane [4Fe-4S] clusters composed of fused [3Fe-4S]-[2Fe-2S] units sharing 1 iron (Fe) and 1 sulfur (S), which were coordinated at the CCG motifs. Soaking experiments showed that the heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Rerouting Cellular Electron Flux To Increase the Rate of Biological Methane Production

PubMed Central

Catlett, Jennie L.; Ortiz, Alicia M.

2015-01-01

Methanogens are anaerobic archaea that grow by producing methane, a gas that is both an efficient renewable fuel and a potent greenhouse gas. We observed that overexpression of the cytoplasmic heterodisulfide reductase enzyme HdrABC increased the rate of methane production from methanol by 30% without affecting the growth rate relative to the parent strain. Hdr enzymes are essential in all known methane-producing archaea. They function as the terminal oxidases in the methanogen electron transport system by reducing the coenzyme M (2-mercaptoethane sulfonate) and coenzyme B (7-mercaptoheptanoylthreonine sulfonate) heterodisulfide, CoM-S-S-CoB, to regenerate the thiol-coenzymes for reuse. In Methanosarcina acetivorans, HdrABC expression caused an increased rate of methanogenesis and a decrease in metabolic efficiency on methylotrophic substrates. When acetate was the sole carbon and energy source, neither deletion nor overexpression of HdrABC had an effect on growth or methane production rates. These results suggest that in cells grown on methylated substrates, the cell compensates for energy losses due to expression of HdrABC with an increased rate of substrate turnover and that HdrABC lacks the appropriate electron donor in acetate-grown cells. PMID:26162885

Studies on the "Aerobic" Acetyl-Coenzyme A Synthetase of Saccharomyces Cerevisiae: Purification, Crystallization, and Physical Properties of the Enzyme

NASA Technical Reports Server (NTRS)

Satyanarayana, T.; Klein, Harold P.

1976-01-01

A procedure for the purification of a stable acetyl-coenzyme A synthetase (ACS) from aerobic cells of Saccharomyces cerevisiae is presented. The steps include differential centrifugation, solubilization of the bound enzyme from the crude mitochondrial fraction, ammonium sulfate fractionation, crystallization to constant specific activity from ammonium sulfate solutions followed by Bio-Gel A-1.5 m column chromatography. The resulting enzyme preparation is homogeneous as judged by chromatography on Bio-Gel columns, QAE-Sephadex A-50 anion exchange columns, analytical ultracentrifugal studies, and polyacrylamide gel electrophoresis. Sedimentation velocity runs revealed a single symmetric peak with an s(sub (20,w)) value of 10.6. The molecular weight of the native enzyme, as determined by gel filtration and analytical ultracentrifugation, is 250,000 +/- 500. In polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the molecular weight of the single polypeptide chain is 83,000 +/- 500. The purified enzyme is inhibited by palmityl-coenzyme A with a Hill interaction coefficient, n, of 2.88. These studies indicate that the ACS of aerobic Saccharomyces cerevisiae is composed of three subunits of identical or nearly identical size.

Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ness, Gene C., E-mail: gness@hsc.usf.edu; Edelman, Jeffrey L.; Brooks, Patricia A.

2012-03-30

Highlights: Black-Right-Pointing-Pointer siRNAs to tristetraprolin blocks transcription of HMGR in vivo in rat liver. Black-Right-Pointing-Pointer siRNAs to tristetraprolin inhibits insulin activation of HMGR transcription. Black-Right-Pointing-Pointer Insulin acts to rapidly increase tristetraprolin in liver nuclear extracts. -- Abstract: Several AU-rich RNA binding element (ARE) proteins were investigated for their possible effects on transcription of hepatic 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGR) in normal rats. Using in vivo electroporation, four different siRNAs to each ARE protein were introduced together with HMGR promoter (-325 to +20) luciferase construct and compared to saline controls. All four siRNAs to tristetraprolin (TTP) completely eliminated transcription from themore » HMGR promoter construct. Since insulin acts to rapidly increase hepatic HMGR transcription, the effect of TTP siRNA on induction by insulin was tested. The 3-fold stimulation by insulin was eliminated by this treatment. In comparison, siRNA to AU RNA binding protein/enoyl coenzyme A hydratase (AUH) had no effect. These findings indicate a role for TTP in the insulin-mediated activation of hepatic HMGR transcription.« less

[Interactions of food and drug metabolism].

PubMed

Delzenne, N M; Verbeeck, R K

2001-01-01

The nutritional state, and/or the ingestion of specific nutrients, is/are able to modify drug disposition, by interfering with drug absorption, distribution, storage, and metabolism. Recent data report that nutrients interfere with drug metabolism either by modifying key enzymes of phase I (cytochromeP450 dependent mixed function oxidase) and II (glucuronosyl, sulfonyl- ... transferases), or by modulating coenzymes availability (NADPH, UDPglucuronic acid...). Food components involved in drug metabolism modifications are either macro-nutrients (carbohydrates, lipids, proteins, ethanol), micronutriments (vitamins, minerals), or phytochemicals. Drug-nutrients interactions may be beneficials, and thus could constitute, i.e. a way to improve drug therapeutic index, or generate adverse effects.

Quantifying Preferences of Farmers and Veterinarians for National Animal Health Programs: The Example of Bovine Mastitis and Antimicrobial Usage in Switzerland

PubMed Central

van den Borne, Bart H. P.; van Soest, Felix J. S.; Reist, Martin; Hogeveen, Henk

2017-01-01

Bovine udder health in Switzerland is of a relatively high level. However, antimicrobial usage (AMU) seems high in comparison to other European countries also. A new udder health and AMU improvement program could improve this situation but it is uncertain whether there is support from the field. This study aimed to quantify preferences of dairy farmers and veterinarians for the start and design characteristics of a new national udder health and AMU improvement program in Switzerland. A total of 478 dairy farmers and 98 veterinarians completed an online questionnaire. Questions on their demographics and their mindset toward AMU were complemented with an adaptive choice-based conjoint interview, a novel conjoint analysis technique to quantify preferences of respondents for characteristics of a product for which multiple trade-off decisions must be made (here a bovine udder health and AMU improvement program). The conjoint analysis was followed by a multivariate multiple regression analysis to identify groups of respondents with different program design preferences. Logistic regression models were used to associate covariates with respondents’ preference to start a new udder health and AMU improvement program. Most farmers (55%) and veterinarians (62%) were in favor of starting a new voluntary udder health and AMU improvement program, but the program design preferences agreed moderately between the two stakeholder groups. Farmers preferred an udder health and AMU improvement program that did not contain a penalty system for high AMU, was voluntary for all dairy herds, and aimed to simultaneously improve udder health and reduce AMU. Veterinarians preferred a program that had the veterinary organization and the government taking the lead in program design decision making, did not contain a penalty system for high AMU, and aimed to simultaneously improve udder health and reduce AMU. Differences between groups of farmers and veterinarians concerning their start preference were identified. Also, the magnitude of various program design preferences changed for farmers with different opinions toward AMU. The information obtained from this study may support the decision-making process and the communication to the field afterward, when discussing national strategies to improve udder health and AMU in Switzerland. PMID:28626750

Structural Insight into Methyl-Coenzyme M Reductase Chemistry using Coenzyme B Analogues†,‡

PubMed Central

Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M.

2011-01-01

Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis; the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme, and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from analogues of methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 Å long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 Å predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 Å. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues; pentanoyl-, hexanoyl-, octanoyl- and nonanoyl- derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH and CoB9SH respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH, but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues react with Ni(III)-methyl; a proposed MCR catalytic intermediate of methanogenesis. The CoB8SH thiolate is 2.6 Å closer to the nickel than that of CoBSH, but the additional carbon of CoB9SH only decreases the nickel thiolate distance a further 0.3 Å. Although the analogues did not induce any structural changes in the substrate channel, the thiolates appeared to preferentially bind at two distinct positions in the channel; one being the previously observed CoBSH thiolate position, and the other being at a hydrophobic annulus of residues that lines the channel proximal to the nickel. PMID:20707311

Boosting autofermentation rates and product yields with sodium stress cycling: application to production of renewable fuels by cyanobacteria.

PubMed

Carrieri, Damian; Momot, Dariya; Brasg, Ian A; Ananyev, Gennady; Lenz, Oliver; Bryant, Donald A; Dismukes, G Charles

2010-10-01

Sodium concentration cycling was examined as a new strategy for redistributing carbon storage products and increasing autofermentative product yields following photosynthetic carbon fixation in the cyanobacterium Arthrospira (Spirulina) maxima. The salt-tolerant hypercarbonate strain CS-328 was grown in a medium containing 0.24 to 1.24 M sodium, resulting in increased biosynthesis of soluble carbohydrates to up to 50% of the dry weight at 1.24 M sodium. Hypoionic stress during dark anaerobic metabolism (autofermentation) was induced by resuspending filaments in low-sodium (bi)carbonate buffer (0.21 M), which resulted in accelerated autofermentation rates. For cells grown in 1.24 M NaCl, the fermentative yields of acetate, ethanol, and formate increase substantially to 1.56, 0.75, and 1.54 mmol/(g [dry weight] of cells·day), respectively (36-, 121-, and 6-fold increases in rates relative to cells grown in 0.24 M NaCl). Catabolism of endogenous carbohydrate increased by approximately 2-fold upon hypoionic stress. For cultures grown at all salt concentrations, hydrogen was produced, but its yield did not correlate with increased catabolism of soluble carbohydrates. Instead, ethanol excretion becomes a preferred route for fermentative NADH reoxidation, together with intracellular accumulation of reduced products of acetyl coenzyme A (acetyl-CoA) formation when cells are hypoionically stressed. In the absence of hypoionic stress, hydrogen production is a major beneficial pathway for NAD(+) regeneration without wasting carbon intermediates such as ethanol derived from acetyl-CoA. This switch presumably improves the overall cellular economy by retaining carbon within the cell until aerobic conditions return and the acetyl unit can be used for biosynthesis or oxidized via respiration for a much greater energy return.

Effects of nutraceutical diet integration, with coenzyme Q10 (Q-Ter multicomposite) and creatine, on dyspnea, exercise tolerance, and quality of life in COPD patients with chronic respiratory failure

PubMed Central

2013-01-01

Background The protein-calorie malnutrition, resulting in muscle mass loss, frequently occurs in severe COPD patients with chronic respiratory failure (CRF), causing dyspnea, reduced exercise tolerance and impaired quality of life. The cause of this occurrence is an intake-output energy imbalance. A documented deficit of phosphocreatine and reduced mithocondrial energy production can contribute to this imbalance. Aim of this study is to verify whether a dietary supplementation with creatine and coenzyme Q10, important mitochondrial function factors, is able to influence this mechanism leading to a dyspnea reduction and improving exercise tolerance and quality of life. Methods 55 COPD patients with chronic respiratory failure (in long term O2 therapy), in stable phase of the disease and without severe comorbidities were assigned (double-blind, randomized) to: group A (30 patients) with daily dietary supplementation with Creatine 340 mg + 320 mg Coenzyme Q-Ter (Eufortyn®, Scharper Therapeutics Srl) for 2 months whereas Group B (25 patients) received placebo. All patients continued the same diet, rehabilitation and therapy during the study. At recruitment (T0) and after 2 months (T1), patients were submitted to medical history, anthropometry (BMI), bioelectrical impedance, arterial blood gas analysis, evaluation of dyspnea (VAS, Borg, BDI, MRC) and functional independence (ADL), 6-minute walk test (6MWT) and quality of life questionnaire (SGRQ). At 6 months and 1 year, a telephone follow up was conducted on exacerbations number. Results No significant difference was detected at baseline (T0) in the 2 groups. After 2 months of therapy (T1) the FFMI increased in the daily dietary supplementation group (+ 3.7 %) and decreased in the placebo group (- 0.6 %), resulting in a statistically significant (p < 0.001) treatment difference. Statistically significant treatment differences, favouring daily dietary supplementation group, were also seen for the 6MWT comparison. Group A patients also showed significant: 1) improvement in the degree of dyspnea (VAS: p < 0.05; Borg: p < 0.05; MRC: p < 0.001; BDI1: p < 0.05; BDI3: p < 0.03), and independence level in activities of daily living (p < 0.03); 2) improvement in quality of life in activity section (- 6.63 pt) and in total score (- 5.43 pt); 3) exacerbation number decrease (p < 0.02). No significant differences were found (end of study vs baseline) in group B. Conclusions The nutraceutical diet integration with Q-Ter and creatine, in COPD patients with CRF in O2TLT induced an increasing lean body mass and exercise tolerance, reducing dyspnea, quality of life and exacerbations. These results provide a first demonstration that acting on protein synthesis and muscular efficiency can significantly modify the systemic consequences of the disease. PMID:23800154

[Nutrition and dietary supplements in neurological diseases].

PubMed

Erbguth, F; Himmerich, H

2014-12-01

"Healthy" diets and supplements are widely used for prevention and disease modification in vascular, inflammatory and degenerative neurological diseases. Apart from a large number of cross-sectional and prospective cohort studies, there are only few interventional studies on individual dietary measures. A recent study confirmed the stroke preventive effect of a Mediterranean diet rich in olive oil and nuts; a ketogenic diet reduces seizure frequency in epilepsy. Supplementation of riboflavin, magnesium and coenzyme Q10 are probably effective in migraine prophylaxis. Creatine can improve muscle strength in muscular dystrophy and myositis. There is insufficient evidence to recommend any of the many dietary supplements, such as vitamins, omega-3 fatty acids and other substances for the prevention or improvement of all other neurological diseases. This review critically evaluates the present data on the role of nutrition and dietary supplements in neurological diseases.

Integrated treatment approach improves cognitive function in demented and clinically depressed patients.

PubMed

Bragin, Valentin; Chemodanova, Marina; Dzhafarova, Narmina; Bragin, Ilya; Czerniawski, Jennifer L; Aliev, Gjumrakch

2005-01-01

The purpose of this study was to evaluate the efficacy of an integrative treatment approach on cognitive performance. The study sample comprised 35 medically ill patients (20 male, 15 female) with an average age of 71.05, who were diagnosed with mild dementia and depression. These patients were evaluated at baseline and at six, 12, and 24 months of treatment, which included antidepressants (sertraline, citalopram, or venlafaxine XR, alone or in combination with bupropion XR), cholinesterase inhibitors (donepezil, rivastigmine or galantamine), as well as vitamins and supplements (multivitamins, vitamin E, alpha-lipoic acid, omega-3 and coenzyme Q-10). Patients were encouraged to modify their diet and lifestyle and perform mild physical exercises. Results show that the integrative treatment not only protracted cognitive decline for 24 months but even improved cognition, especially memory and frontal lobe functions.

Effect of the additives on clouding behavior and thermodynamics of coenzyme Q10-Kolliphor HS15 micelle aqueous solutions

NASA Astrophysics Data System (ADS)

Hu, Li; Zhang, Jing; Zhu, Chao; Pan, Hong-chun; Liu, Hong

2017-11-01

Herein we investigate the effect of different additives (electrolytes, amino acids, PEG, and sugars) on the cloud points (CP) of coenzyme Q10 (CoQ10) - Kolliphor HS15 (HS15) micelle aqueous solutions. The CP values were decreased with the increase of electrolytes and sugars, following: CPAl3+ < CPMg2+ < CPCa2+ < CPNa+ < CPK+ < CPNH4+; CPdisaccharide < CPmonosaccharide. The presences of Arginine and Tryptophan significantly increased the CP; while the other amino acids reduced the CP. A depression of CP for CoQ10-HS15 micelle solution with PEG was molecular weight of PEG dependent. The significant thermodynamic parameters were also evaluated and discussed.

Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities.

PubMed

Wang, H X; Ng, T B

1999-01-01

This article reviews compounds of botanical origin which are capable of lowering plasma levels of glucose and cholesterol and blood pressure, as well as compounds inhibiting atherosclerosis and thrombosis. Hypoglycemic natural products comprise flavonoids, xanthones, triterpenoids, alkaloids, glycosides, alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides and peptides. Hypotensive compounds include flavonoids, diterpenes, alkaloids, glycosides, polysaccharides and proteins. Among natural products with hypocholesterolemic activity are beta-carotene, lycopene, cycloartenol, beta-sitosterol, sitostanol, saponin, soybean protein, indoles, dietary fiber, propionate, mevinolin (beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor) and polysaccharides. Heparins, flavonoids, tocotrienols, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins), garlic compounds and fungal proteases exert antithrombotic action. Statins and garlic compounds also possess antiatherosclerotic activity.

Bioinspired Design of Alcohol Dehydrogenase@nano TiO₂ Microreactors for Sustainable Cycling of NAD⁺/NADH Coenzyme.

PubMed

Lin, Sen; Sun, Shiyong; Wang, Ke; Shen, Kexuan; Ma, Biaobiao; Ren, Yuquan; Fan, Xiaoyu

2018-02-24

The bioinspired design and construction of enzyme@capsule microreactors with specific cell-like functionality has generated tremendous interest in recent years. Inspired by their fascinating complexity, scientists have endeavored to understand the essential aspects of a natural cell and create biomimicking microreactors so as to immobilize enzymes within the hierarchical structure of a microcapsule. In this study, simultaneous encapsulation of alcohol dehydrogenase (ADH) was achieved during the preparation of microcapsules by the Pickering emulsion method using amphiphilic modified TiO₂ nanoparticles (NPs) as building blocks for assembling the photocatalytic microcapsule membrane. The ADH@TiO₂ NP microreactors exhibited dual catalytic functions, i.e., spatially confined enzymatic catalysis and the membrane-associated photocatalytic oxidation under visible light. The sustainable cycling of nicotinamide adenine dinucleotide (NAD) coenzyme between NADH and NAD⁺ was realized by enzymatic regeneration of NADH from NAD⁺ reduction, and was provided in a form that enabled further photocatalytic oxidation to NAD⁺ under visible light. This bioinspired ADH@TiO₂ NP microreactor allowed the linking of a semiconductor mineral-based inorganic photosystem to enzymatic reactions. This is a first step toward the realization of sustainable biological cycling of NAD⁺/NADH coenzyme in synthetic functional microsystems operating under visible light irradiation.

Structural Characterization of a Human-Type Corrinoid Adenosyltransferase Confirms That Coenzyme B[subscript 12] Is Synthesized through a Four-Coordinate Intermediate

DOE Office of Scientific and Technical Information (OSTI.GOV)

St. Maurice, Martin; Mera, Paola; Park, Kiyoung

ATP:cob(I)alamin adenosyltransferases (ACAs) catalyze the transfer of the 5{prime}-deoxyadenosyl moiety from ATP to the upper axial ligand position of cobalamin in the synthesis of coenzyme B{sub 12}. For the ACA-catalyzed reaction to proceed, cob(II)alamin must be reduced to cob(I)alamin in the enzyme active site. This reduction is facilitated through the generation of a four-coordinate cob(II)alamin intermediate on the enzyme. We have determined the high-resolution crystal structure of a human-type ACA from Lactobacillus reuteri with a four-coordinate cob(II)alamin bound in the enzyme active site and with the product, adenosylcobalamin, partially occupied in the active site. The assembled structures represent snapshots ofmore » the steps in the ACA-catalyzed formation of the cobalt-carbon bond of coenzyme B{sub 12}. The structures define the corrinoid binding site and provide visual evidence for a base-off, four-coordinate cob(II)alamin intermediate. The complete structural description of ACA-mediated catalysis reveals the molecular features of four-coordinate cob(II)alamin stabilization and provides additional insights into the molecular basis for dysfunction in human patients suffering from methylmalonic aciduria.« less

Purification of a Jojoba Embryo Fatty Acyl-Coenzyme A Reductase and Expression of Its cDNA in High Erucic Acid Rapeseed

PubMed Central

Metz, James G.; Pollard, Michael R.; Anderson, Lana; Hayes, Thomas R.; Lassner, Michael W.

2000-01-01

The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes. PMID:10712526

Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rapeseed.

PubMed

Metz, J G; Pollard, M R; Anderson, L; Hayes, T R; Lassner, M W

2000-03-01

The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes.

Electrochemical Reduction of Carbon Dioxide to Methanol by Direct Injection of Electrons into Immobilized Enzymes on a Modified Electrode.

PubMed

Schlager, Stefanie; Dumitru, Liviu Mihai; Haberbauer, Marianne; Fuchsbauer, Anita; Neugebauer, Helmut; Hiemetsberger, Daniela; Wagner, Annika; Portenkirchner, Engelbert; Sariciftci, Niyazi Serdar

2016-03-21

We present results for direct bio-electrocatalytic reduction of CO2 to C1 products using electrodes with immobilized enzymes. Enzymatic reduction reactions are well known from biological systems where CO2 is selectively reduced to formate, formaldehyde, or methanol at room temperature and ambient pressure. In the past, the use of such enzymatic reductions for CO2 was limited due to the necessity of a sacrificial co-enzyme, such as nicotinamide adenine dinucleotide (NADH), to supply electrons and the hydrogen equivalent. The method reported here in this paper operates without the co-enzyme NADH by directly injecting electrons from electrodes into immobilized enzymes. We demonstrate the immobilization of formate, formaldehyde, and alcohol dehydrogenases on one-and-the-same electrode for direct CO2 reduction. Carbon felt is used as working electrode material. An alginate-silicate hybrid gel matrix is used for the immobilization of the enzymes on the electrode. Generation of methanol is observed for the six-electron reduction with Faradaic efficiencies of around 10%. This method of immobilization of enzymes on electrodes offers the opportunity for electrochemical application of enzymatic electrodes to many reactions in which a substitution of the expensive sacrificial co-enzyme NADH is desired. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficiency of emulsifier-free emulsions and emulsions containing rapeseed lecithin as delivery systems for vectorization and release of coenzyme Q10: physico-chemical properties and in vitro evaluation.

PubMed

Kaci, M; Arab-Tehrany, E; Dostert, G; Desjardins, I; Velot, E; Desobry, S

2016-11-01

To improve the encapsulation and release of coenzyme Q10 (CoQ10), emulsifier-free-emulsions were developed with a new emulsification process using high-frequency ultrasound (HFU) at 1.7MHz. Nano-emulsions containing CoQ10 were prepared with or without rapeseed lecithin as an emulsifier. The emulsions prepared with HFU were compared with an emulsion of CoQ10 containing emulsifier prepared with the same emulsification technique as well as with emulsions prepared with low-frequency ultrasound coupled with high-pressure homogenization (LFU+HPH). The physico-chemical properties of the emulsions were determined by average droplet size measurement with nano-droplet tracking analysis, droplet surface charge with ζ potential measurement, surface tension and rheological behaviour. Emulsions made by LFU+HPH with an emulsifier showed lower droplet sizes due to cavitation generated by the HFU process. Surface tension results showed that there was no significant difference between emulsions containing lecithin emulsifier regardless of the preparation process or the inclusion of CoQ10. In vitro biocompatibility tests were performed on human mesenchymal stem cells in order to show the cytotoxicity of various formulations and the efficiency of CoQ10-loaded emulsions. In vitro tests proved that the vectors were not toxic. Furthermore, CoQ10 facilitated a high rate of cell proliferation and metabolic activity especially when in an emulsifier-free formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.

PubMed

El Refaeey, Abdelaziz; Selem, Amal; Badawy, Ahmed

2014-07-01

This prospective randomized controlled trial evaluated the effect of combined oral coenzyme Q10 (CoQ10) and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). A total of 101 infertile women with PCOS resistant to clomiphene citrate were randomized either to combined CoQ10 and clomiphene citrate (51 patients, 82 cycles) or to clomiphene citrate alone (50 patients, 71 cycles). The outcome measures were number of follicles, serum oestradiol, serum progesterone, endometrial thickness and ovulation, clinical pregnancy and miscarriage rates. Numbers of follicles >14 mm and ≥18 mm were significantly higher in the CoQ10 group. Endometrial thickness on the day of human chorionic gonadotrophin was significantly greater in the CoQ10 group (8.82 ± 0.27 mm versus 7.03 ± 0.74 mm). Ovulation occurred in 54/82 cycles (65.9%) in the CoQ10 group and 11/71 cycles (15.5%) in the control group. Clinical pregnancy rate was significantly higher in the CoQ10 group (19/51, 37.3%) versus the control group (3/50, 6.0%). Combination of CoQ10 and clomiphene citrate in the treatment of clomiphene-citrate-resistant PCOS patients improves ovulation and clinical pregnancy rates. It is an effective and safe option and can be considered before gonadotrophin therapy or laparoscopic ovarian drilling. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

PubMed

Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

2014-04-01

Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

Beta-cell function in individuals carrying the mitochondrial tRNA leu (UUR) mutation.

PubMed

Salles, João Eduardo; Kasamatsu, Teresa S; Dib, Sérgio A; Moisés, Regina S

2007-01-01

To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response. Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response. Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. The first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones. We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. In addition, our data suggest that this could be a functional defect.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

PubMed Central

Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2016-01-01

Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

A comparison of the relative antioxidant potency of L-ergothioneine and idebenone.

PubMed

Dong, Kelly K; Damaghi, Niusha; Kibitel, Jeannie; Canning, Matthew T; Smiles, Kenneth A; Yarosh, Daniel B

2007-09-01

L-ergothioneine (EGT) is a stable antioxidant found in food plants as well as in animal tissue undergoing relatively high levels of oxidative stress. Idebenone is a stable analog of the antioxidant coenzyme Q(10). All are potent antioxidants found in skincare products, but their relative potencies are not well described. To establish the physiological relevance of EGT by examining transcription of the EGT transporter gene OCTN-1 and production of the receptor protein in skin fibroblasts. In addition, to compare the inhibition of lipid peroxide formation by coenzyme Q(10) and EGT. Furthermore, to compare the peroxide-scavenging abilities of EGT and idebenone in both simple solution and in cell cultures exposed to ultraviolet A (UVA). OCTN-1 expression and production in cultured fibroblasts were measured through real-time reverse transcription-PCR and Western blotting, respectively. Alloxan-induced lipid peroxidation in liposomes was used to evaluate the inhibition of lipid peroxide formation. The abilities of EGT and idebenone to directly scavenge hydroxyl radicals produced by H(2)O(2 )were determined. Finally, we irradiated fibroblasts with UVA340 radiation and compared antioxidant capabilities to scavenge free radicals. We found that OCTN-1 is expressed and readily detectable in cultured human fibroblasts. EGT was more efficient in inhibiting lipid peroxide formation than coenzyme Q(10) or idebenone. Samples treated with EGT had significantly less peroxide than those treated with idebenone 120 min after adding the antioxidants to H(2)O(2). EGT acted significantly quicker and more efficiently in capturing reactive oxygen species (ROS) after UVA340 irradiation. EGT is a natural skin antioxidant, as evidenced by the presence of the EGT transporter in fibroblasts. EGT is a more powerful antioxidant than either coenzyme Q(10) or idebenone due to its relatively greater efficiency in directly scavenging free radicals and in protecting cells from UV-induced ROS.

Potency of pre-post treatment of coenzyme Q10 and melatonin supplement in ameliorating the impaired fatty acid profile in rodent model of autism.

PubMed

El-Ansary, Afaf; Al-Ghamdi, Mashael; Bhat, Ramesa Shafi; Al-Daihan, Sooad; Al-Ayadhi, Laila

2016-01-01

Abnormalities in fatty acid metabolism and membrane fatty acid composition play a part in a wide range of neurodevelopmental and psychiatric disorders. Altered fatty acid homeostasis as a result of insufficient dietary supplementation, genetic defects, the function of enzymes involved in their metabolism, or mitochondrial dysfunction contributes to the development of autism. This study evaluates the association of altered brain lipid composition and neurotoxicity related to autism spectrum disorders in propionic acid (PA)-treated rats. Forty-eight young male western albino rats were used in this study. They were grouped into six equal groups with eight rats in each. The first group received only phosphate buffered saline (control group). The second group received a neurotoxic dose of buffered PA (250 mg/kg body weight/day for 3 consecutive days). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for 1 week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for 1 week prior to PA (protected groups). Methyl esters of fatty acid were extracted with hexane, and the fatty acid composition of the extract was analyzed on a gas chromatography. The obtained data proved that fatty acids are altered in brain tissue of PA-treated rats. All saturated fatty acids were increased while all unsaturated fatty acids were significantly decreased in the PA-treated group and relatively ameliorated in the pre-post melatonin and coenzyme Q groups. Melatonin and coenzyme Q were effective in restoring normal level of most of the impaired fatty acids in PA-intoxicated rats which could help suggest both as supplements to ameliorate the autistic features induced in rat pups.

The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

PubMed

Contin, Mario; Flor, Sabrina; Martinefski, Manuela; Lucangioli, Silvia; Tripodi, Valeria

2014-01-07

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 μL of sample mixed with 30 mg of MIP and 600 μL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 μg g(-1), respectively, and a linear range between 7.5 and 150 μg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

European organic dairy farmers' preference for animal health management within the farm management system.

PubMed

van Soest, F J S; Mourits, M C M; Hogeveen, H

2015-11-01

The expertise and knowledge of veterinary advisors on improving animal health management is key towards a better herd health status. However, veterinary advisors are not always aware of the goals and priorities of dairy farmers. To dairy farmers animal health is only one aspect of farm management and resources may be allocated to other more preferred areas. Veterinary advisors may experience this as non-compliant with their advice. To explore the preferences of European Union (EU) organic dairy farmers for improved animal health management relative to other farm management areas an adaptive conjoint analysis (ACA) was performed. A total of 215 farmers participated originating from organic dairy farms in France (n = 70), Germany (n = 60), Spain (n = 28) and Sweden (n = 57). The management areas udder health and claw health represented animal health management whereas barn, calf and pasture management represented potential conflicting management areas. Results indicate that EU organic dairy farmers differ in their preferences for improved animal health management within the farming system. In general, improved calf management was the most preferred area and improved claw health management was found to be least preferred, the remaining areas were of intermediate interest. Cluster analyses on claw health measures and udder health measures resulted in respectively seven and nine distinct preference profiles. The results indicate a high degree of variation in farmers' preference, which cannot be explained by the typical herd characteristics. With the individual preferences revealed by ACA, a veterinary advisor can now find out whether his intended advice is directed at a favourable or unfavourable management area of the farmer. If the latter is the case the veterinarian should first create awareness of the problem to the farmer. Insights in individual farmers preferences will allow veterinary advisors to better understand why farmers were incompliant with their advice and improve their advice by showing, for example, the potential benefits of their advice.

Centronuclear myopathy in a Border collie dog.

PubMed

Eminaga, S; Cherubini, G B; Shelton, G D

2012-10-01

A two-year old, male entire Border collie was presented with a one-year history of exercise-induced collapsing on the pelvic limbs. Physical examination revealed generalised muscle atrophy. Neurological examination supported a generalised neuromuscular disorder. Electromyography revealed spontaneous electrical activity in almost all muscles. Unfixed and formaldehyde-fixed biopsy samples were collected from the triceps brachii, longissimus and vastus lateralis muscles. Histopathological, histochemical and ultrastructural examinations of biopsy specimens were consistent with either centronuclear or myotubular myopathy. The dog clinically improved with supportive treatment with L-carnitine, co-enzyme Q10 and vitamin B compound. To the authors' knowledge, this is the first report of centronuclear/myotubular myopathy in a Border collie. © 2012 British Small Animal Veterinary Association.

Do quality improvement collaboratives' educational components match the dominant learning style preferences of the participants?

PubMed

Weggelaar-Jansen, Anne Marie; van Wijngaarden, Jeroen; Slaghuis, Sarah-Sue

2015-06-20

Quality improvement collaboratives are used to improve healthcare by various organizations. Despite their popularity literature shows mixed results on their effectiveness. A quality improvement collaborative can be seen as a temporary learning organization in which knowledge about improvement themes and methods is exchanged. In this research we studied: Does the learning approach of a quality improvement collaborative match the learning styles preferences of the individual participants and how does that affect the learning process of participants? This research used a mixed methods design combining a validated learning style questionnaire with data collected in the tradition of action research methodology to study two Dutch quality improvement collaboratives. The questionnaire is based on the learning style model of Ruijters and Simons, distinguishing five learning style preferences: Acquisition of knowledge, Apperception from others, Discovery of new insights, Exercising in fictitious situations and Participation with others. The most preferred learning styles of the participants were Discovery and Participation. The learning style Acquisition was moderately preferred and Apperception and Exercising were least preferred. The educational components of the quality improvement collaboratives studied (national conferences, half-day learning sessions, faculty site visits and use of an online tool) were predominantly associated with the learning styles Acquisition and Apperception. We observed a decrease in attendance to the learning activities and non-conformance with the standardized set goals and approaches. We conclude that the participants' satisfaction with the offered learning approach changed over time. The lacking match between these learning style preferences and the learning approach in the educational components of the quality improvement collaboratives studied might be the reason why the participants felt they did not gain new insights and therefore ceased their participation in the collaborative. This study provides guidance for future organisers and participants of quality improvement collaboratives about which learning approaches will best suit the participants and enhance improvement work.

The Value of Coenzyme Q10 Determination in Mitochondrial Patients

PubMed Central

Yubero, Delia; Allen, George; Artuch, Rafael; Montero, Raquel

2017-01-01

Coenzyme Q10 (CoQ) is a lipid that is ubiquitously synthesized in tissues and has a key role in mitochondrial oxidative phosphorylation. Its biochemical determination provides insight into the CoQ status of tissues and may detect CoQ deficiency that can result from either an inherited primary deficiency of CoQ metabolism or may be secondary to different genetic and environmental conditions. Rapid identification of CoQ deficiency can also allow potentially beneficial treatment to be initiated as early as possible. CoQ may be measured in different specimens, including plasma, blood mononuclear cells, platelets, urine, muscle, and cultured skin fibroblasts. Blood and urinary CoQ also have good utility for CoQ treatment monitoring. PMID:28338638

A new mutation in MT-ND1 m.3928G>C p.V208L causes Leigh disease with infantile spasms.

PubMed

Wray, Carter D; Friederich, Marisa W; du Sart, Desiree; Pantaleo, Sarah; Smet, Joél; Kucera, Cathlin; Fenton, Laura; Scharer, Gunter; Van Coster, Rudy; Van Hove, Johan L K

2013-11-01

New mutations in mitochondrial DNA encoded genes of complex I are rarely reported. An infant developed Leigh disease with infantile spasms. Complex I enzyme activity was deficient and response to increasing coenzyme Q concentrations was reduced. Complex I assembly was intact. A new mutation in MT-ND1 m.3928G>C p.V208L, affecting a conserved amino acid in a critical domain, part of the coenzyme Q binding pocket, was present at high heteroplasmy. The unaffected mother did not carry measurable mutant mitochondrial DNA, but concern remained for gonadal mosaicism. Prenatal testing was possible for a subsequent sibling. The ND1 p.V208L mutation causes Leigh disease. © 2013.

Nanoscale semiconducting silicon as a nutritional food additive

NASA Astrophysics Data System (ADS)

Canham, L. T.

2007-05-01

Very high surface area silicon powders can be realized by high energy milling or electrochemical etching techniques. Such nanoscale silicon structures, whilst biodegradable in the human gastrointestinal tract, are shown to be remarkably stable in most foodstuffs and beverages. The potential for using silicon to improve the shelf life and bioavailability of specific nutrients in functional foods is highlighted. Published drug delivery data implies that the nanoentrapment of hydrophobic nutrients will significantly improve their dissolution kinetics, through a combined effect of nanostructuring and solid state modification. Nutrients loaded to date include vitamins, fish oils, lycopene and coenzyme Q10. In addition, there is growing published evidence that optimized release of orthosilicic acid, the biodegradation product of semiconducting silicon in the gut, offers beneficial effects with regard bone health. The utility of nanoscale silicon in the nutritional field shows early promise and is worthy of much further study.

Vitamin B supplementation for diabetic peripheral neuropathy

PubMed Central

Jayabalan, Bhavani; Low, Lian Leng

2016-01-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

Influence of ultrasonication on anaerobic bioconversion of sludge.

PubMed

Mao, Taohong; Show, Kuan-Yeow

2007-04-01

The influence of ultrasonication on hydrolysis, acidogenesis, and methanogenesis in anaerobic decomposition of sludge was investigated. The sonicated sludge exhibited prehydrolysis and preacidogenesis effects in the anaerobic decomposition process. First-order hydrolysis rates increased from 0.0384 day(-1) in the control digester to 0.0672 day(-1) in the digester fed, with sludge sonicated at 0.52 W/mL. The sonication appeared to be ineffective in relation to acidogenesis reaction rates, but it provided a better buffering capacity to diminish the adverse effect of acidification. Digesters fed with sonicated sludge demonstrated enhanced methanogenesis over the control unit. Determination by coenzyme F420 verified that sonication is able to promote the growth of methanogenic biomass and facilitate a positive methanogenic microbial development in suppressing the initial methanogenesis limitation. The results suggest that ultrasonication could enhance anaerobic decomposition of sludge, resulting in an accelerated bioconversion, improved organics degradation, improved biogas production, and increased methane content.

Regulation of autotrophic CO2 fixation in the archaeon Thermoproteus neutrophilus.

PubMed

Ramos-Vera, W Hugo; Labonté, Valérie; Weiss, Michael; Pauly, Julia; Fuchs, Georg

2010-10-01

Thermoproteus neutrophilus, a hyperthermophilic, chemolithoautotrophic, anaerobic crenarchaeon, uses a novel autotrophic CO(2) fixation pathway, the dicarboxylate/hydroxybutyrate cycle. The regulation of the central carbon metabolism was studied on the level of whole cells, enzyme activity, the proteome, transcription, and gene organization. The organism proved to be a facultative autotroph, which prefers organic acids as carbon sources that can easily feed into the metabolite pools of this cycle. Addition of the preferred carbon sources acetate, pyruvate, succinate, and 4-hydroxybutyrate to cultures resulted in stimulation of the growth rate and a diauxic growth response. The characteristic enzyme activities of the carbon fixation cycle, fumarate hydratase, fumarate reductase, succinyl coenzyme A (CoA) synthetase, and enzymes catalyzing the conversion of succinyl-CoA to crotonyl-CoA, were differentially downregulated in the presence of acetate and, to a lesser extent, in the presence of other organic substrates. This regulation pattern correlated well with the differential expression profile of the proteome as well as with the transcription of the encoding genes. The genes encoding phosphoenolpyruvate (PEP) carboxylase, fumarate reductase, and four enzymes catalyzing the conversion of succinyl-CoA to crotonyl-CoA are clustered. Two putative operons, one comprising succinyl-CoA reductase plus 4-hydroxybutyrate-CoA ligase genes and the other comprising 4-hydroxybutyryl-CoA dehydratase plus fumarate reductase genes, were divergently transcribed into leaderless mRNAs. The promoter regions were characterized and used for isolating DNA binding proteins. Besides an Alba protein, a 18-kDa protein characteristic for autotrophic Thermoproteales that bound specifically to the promoter region was identified. This system may be suitable for molecular analysis of the transcriptional regulation of autotrophy-related genes.

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

PubMed

Latkovskis, Gustavs; Saripo, Vita; Sokolova, Emma; Upite, Dana; Vanaga, Ilona; Kletnieks, Ugis; Erglis, Andrejs

2016-01-01

Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (P<0.001 and P=0.018, respectively). Muscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial

PubMed Central

Larijani, Vahid Nabavi; Ahmadi, Naser; Zeb, Irfan; Khan, Faraz; Flores, Ferdinand; Budoff, Matthew

2014-01-01

Objective Aged garlic extract (AGE) is associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement. Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial function. A stressful lifestyle is a well-known risk factor for the presence and progression of atherosclerosis. This study investigated the effect of AGE plus CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and endothelial function measured by digital thermal monitoring (DTM) in firefighters. Methods Sixty-five Los-Angeles County firefighters who met the eligibility criteria were enrolled in this placebo-controlled, double-blinded randomized trial. The firefighters were randomized to four tablets of AGE (300 mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and at the 1-year follow-up. Results There were no significant differences in age, cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for cardiovascular risk factors and statin therapy, the mean decrease in vascular stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P = 0.005). Similarly, the mean increase in the area under the temperature curve, the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with the placebo group (P = 0.01). Conclusion The combination of AGE and CoQ10 was independently associated with significant beneficial effects on vascular elasticity and endothelial function in firefighters with high occupational stress, highlighting the important role of AGE and CoQ10 in atherosclerotic prevention of such individuals. PMID:22858191

Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

PubMed

Nagase, Midori; Yamamoto, Yorihiro; Miyazaki, Yusuke; Yoshino, Hiide

2016-05-01

Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

Loss of Bone Mineral Density Associated with Age in Male Rats Fed on Sunflower Oil Is Avoided by Virgin Olive Oil Intake or Coenzyme Q Supplementation

PubMed Central

Ochoa, Julio J.; Llamas-Elvira, José M.; López-Frías, Magdalena

2017-01-01

The role of dietary fat unsaturation and the supplementation of coenzyme Q have been evaluated in relation to bone health. Male Wistar rats were maintained for 6 or 24 months on two diets varying in the fat source, namely virgin olive oil, rich in monounsaturated fatty acids, or sunflower oil, rich in n-6 polyunsaturated fatty acids. Both dietary fats were supplemented or not with coenzyme Q10 (CoQ10). Bone mineral density (BMD) was evaluated in the femur. Serum levels of osteocalcin, osteopontin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), adrenocorticotropin (ACTH) and parathyroid hormone (PTH), as well as urinary F2-isoprostanes were measured. Aged animals fed on virgin olive oil showed higher BMD than those fed on sunflower oil. In addition, CoQ10 prevented the age-related decline in BMD in animals fed on sunflower oil. Urinary F2-isoprostanes analysis showed that sunflower oil led to the highest oxidative status in old animals, which was avoided by supplementation with CoQ10. In conclusion, lifelong feeding on virgin olive oil or the supplementation of sunflower oil on CoQ10 prevented, at least in part mediated by a low oxidative stress status, the age-related decrease in BMD found in sunflower oil fed animals. PMID:28661441

Correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis

PubMed Central

Liu, Wenlan; Sun, Zhirong; Qu, Jixu; Yang, Chunning; Zhang, Xiaomin; Wei, Xinxin

2017-01-01

The aim of the present study was to investigate the correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis. Root respiration was determined using a biological oxygen analyzer. Respiration-related enzymes including glucose-6-phosphate dehydrogenase plus 6-phosphogluconate dehydrogenase, phosphohexose isomerase and succinate dehydrogenase, and respiratory pathways were evaluated. Biomass was determined by a drying-weighing method. In addition, the percentage of glycyrrhizic acid was detected using high-performance liquid chromatography. The association between root respiration and the levels of biomass and glycyrrhizic acid was investigated. The glycolysis pathway (EMP), tricarboxylic acid cycle (TCA) and pentose phosphate (PPP) pathway acted concurrently in the roots of G. uralensis. Grey correlation analysis showed that TCA had the strongest correlation (correlation coefficient, 0.8003) with biomass. Starch and acetyl coenzyme A had the closest association with above-ground biomass, while soluble sugar correlated less strongly with above-ground biomass. Grey correlation analysis between biochemical pathways and the intermediates showed that pyruvic acid had the strongest correlation with EMP, while acetyl coenzyme A correlated most strongly with TCA. Among the intermediates and pathways, pyruvic acid and EMP exhibited the greatest correlation with glycyrrhizic acid, while acetyl coenzyme A and TCA correlated with glycyrrhizic acid less closely. The results of this study may aid the cultivation of G. uralensis. However, these results require verification in further studies. PMID:28962162

Coordinated gene expression for pheromone biosynthesis in the pine engraver beetle, Ips pini (Coleoptera: Scolytidae)

NASA Astrophysics Data System (ADS)

Keeling, Christopher I.; Blomquist, Gary J.; Tittiger, Claus

In several pine bark beetle species, phloem feeding induces aggregation pheromone production to coordinate a mass attack on the host tree. Male pine engraver beetles, Ips pini (Say) (Coleoptera: Scolytidae), produce the monoterpenoid pheromone component ipsdienol de novo via the mevalonate pathway in the anterior midgut upon feeding. To understand how pheromone production is regulated in this tissue, we used quantitative real-time PCR to examine feeding-induced changes in gene expression of seven mevalonate pathway genes: acetoacetyl-coenzyme A thiolase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate 5-diphosphate decarboxylase, isopentenyl-diphosphate isomerase, geranyl-diphosphate synthase (GPPS), and farnesyl-diphosphate synthase (FPPS). In males, expression of all these genes significantly increased upon feeding. In females, the expression of the early mevalonate pathway genes (up to and including the isomerase) increased significantly, but the expression of the later genes (GPPS and FPPS) was unaffected or decreased upon feeding. Thus, feeding coordinately regulates expression of the mevalonate pathway genes necessary for pheromone biosynthesis in male, but not female, midguts. Furthermore, basal mRNA levels were 5- to 41-fold more abundant in male midguts compared to female midguts. This is the first report of coordinated regulation of mevalonate pathway genes in an invertebrate model consistent with their sex-specific role in de novo pheromone biosynthesis.

Correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis.

PubMed

Liu, Wenlan; Sun, Zhirong; Qu, Jixu; Yang, Chunning; Zhang, Xiaomin; Wei, Xinxin

2017-09-01

The aim of the present study was to investigate the correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis . Root respiration was determined using a biological oxygen analyzer. Respiration-related enzymes including glucose-6-phosphate dehydrogenase plus 6-phosphogluconate dehydrogenase, phosphohexose isomerase and succinate dehydrogenase, and respiratory pathways were evaluated. Biomass was determined by a drying-weighing method. In addition, the percentage of glycyrrhizic acid was detected using high-performance liquid chromatography. The association between root respiration and the levels of biomass and glycyrrhizic acid was investigated. The glycolysis pathway (EMP), tricarboxylic acid cycle (TCA) and pentose phosphate (PPP) pathway acted concurrently in the roots of G. uralensis . Grey correlation analysis showed that TCA had the strongest correlation (correlation coefficient, 0.8003) with biomass. Starch and acetyl coenzyme A had the closest association with above-ground biomass, while soluble sugar correlated less strongly with above-ground biomass. Grey correlation analysis between biochemical pathways and the intermediates showed that pyruvic acid had the strongest correlation with EMP, while acetyl coenzyme A correlated most strongly with TCA. Among the intermediates and pathways, pyruvic acid and EMP exhibited the greatest correlation with glycyrrhizic acid, while acetyl coenzyme A and TCA correlated with glycyrrhizic acid less closely. The results of this study may aid the cultivation of G. uralensis . However, these results require verification in further studies.

Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase

DOE PAGES

Chen, Ji-Yun; Liu, Liang; Cao, Chun-Ling; ...

2016-08-23

N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains. Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes. This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine Nε -acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine. Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA). The hNaa60 protein contains an amphipathic helix following its GNAT domain that maymore » contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures. Remarkably, we found that the side-chain of Phe 34 can influence the position of the coenzyme, indicating a new regulatory mechanism involving enzyme, co-factor and substrates interactions. Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.« less

Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL) Related Genes and Expression Profiling during Fruit Development in the Chinese Pear

PubMed Central

Cao, Yunpeng; Han, Yahui; Li, Dahui; Lin, Yi; Cai, Yongping

2016-01-01

In plants, 4-coumarate:coenzyme A ligases (4CLs), comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei) were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS) genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR). We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes. PMID:27775579

Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL) Related Genes and Expression Profiling during Fruit Development in the Chinese Pear.

PubMed

Cao, Yunpeng; Han, Yahui; Li, Dahui; Lin, Yi; Cai, Yongping

2016-10-19

In plants, 4-coumarate:coenzyme A ligases (4CLs), comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei) were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS) genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR). We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes.

Cardioprotective Effect of Coenzyme Q10 on Apoptotic Myocardial Cell Death by Regulation of Bcl-2 Gene Expression

PubMed Central

Khan, Najam Ali; Abid, M.; Ahmad, Aftab; Abuzinadah, Mohammed F.; Basheikh, Mohammed; Kishore, Kamal

2017-01-01

Objectives: To investigate the effect of coenzyme Q10 (CoQ10) on apoptotic myocardial cell death in rat model of heart ischemia and reperfusion I/R injury. Materials and Methods: Eighteen rats (200–250 g) were divided into three groups of 6 rats in each. Group I (sham-operated control group): this is the control group. The animals received the surgical procedure without IR injury or any drug treatment. Group II (I/R group): ischemia was accomplished by the occlusion of coronary artery for 30 min followed by reperfusion for 45 min and Group-III (Coenzyme Q10 treated group): Treated with CoQ10 at a dose of 1 mg/kg, postoperative for 7 days before induction of IR injury. Results: The study revealed that pretreatment with CoQ10 has shown protective effect on apoptotic rat heart and agreed with earlier reports that CoQ10 significantly protects from oxidative stress and cytopathological changes caused by cardiac ischemia followed by reperfusion and attenuated decrease of antioxidant enzymes. Nitric oxide production in the heart of ischemic rats was significantly increased by the pretreatment with CoQ10 in comparison with IR group. Conclusions: CoQ10 protects against cardiac apoptosis induced by IR injury by significantly decreasing the apoptotic DNA and regulating the expression of Bcl-2 gene. PMID:29081620

Structural analysis, plastid localization, and expression of the biotin carboxylase subunit of acetyl-coenzyme A carboxylase from tobacco.

PubMed

Shorrosh, B S; Roesler, K R; Shintani, D; van de Loo, F J; Ohlrogge, J B

1995-06-01

Acetyl-coenzyme A carboxylase (ACCase, EC 6.4.1.2) catalyzes the synthesis of malonyl-coenzyme A, which is utilized in the plastid for de novo fatty acid synthesis and outside the plastid for a variety of reactions, including the synthesis of very long chain fatty acids and flavonoids. Recent evidence for both multifunctional and multisubunit ACCase isozymes in dicot plants has been obtained. We describe here the isolation of a tobacco (Nicotiana tabacum L. cv bright yellow 2 [NT1]) cDNA clone (E3) that encodes a 58.4-kD protein that shares 80% sequence similarity and 65% identity with the Anabaena biotin carboxylase subunit of ACCase. Similar to other biotin carboxylase subunits of acetyl-CoA carboxylase, the E3-encoded protein contains a putative ATP-binding motif but lacks a biotin-binding site (methionine-lysine-methionine or methionine-lysine-leucine). The deduced protein sequence contains a putative transit peptide whose function was confirmed by its ability to direct in vitro chloroplast uptake. The subcellular localization of this biotin carboxylase has also been confirmed to be plastidial by western blot analysis of pea (Pisum sativum), alfalfa (Medicago sativa L.), and castor (Ricinus communis L.) plastid preparations. Northern blot analysis indicates that the plastid biotin carboxylase transcripts are expressed at severalfold higher levels in castor seeds than in leaves.

Structural analysis, plastid localization, and expression of the biotin carboxylase subunit of acetyl-coenzyme A carboxylase from tobacco.

PubMed Central

Shorrosh, B S; Roesler, K R; Shintani, D; van de Loo, F J; Ohlrogge, J B

1995-01-01

Acetyl-coenzyme A carboxylase (ACCase, EC 6.4.1.2) catalyzes the synthesis of malonyl-coenzyme A, which is utilized in the plastid for de novo fatty acid synthesis and outside the plastid for a variety of reactions, including the synthesis of very long chain fatty acids and flavonoids. Recent evidence for both multifunctional and multisubunit ACCase isozymes in dicot plants has been obtained. We describe here the isolation of a tobacco (Nicotiana tabacum L. cv bright yellow 2 [NT1]) cDNA clone (E3) that encodes a 58.4-kD protein that shares 80% sequence similarity and 65% identity with the Anabaena biotin carboxylase subunit of ACCase. Similar to other biotin carboxylase subunits of acetyl-CoA carboxylase, the E3-encoded protein contains a putative ATP-binding motif but lacks a biotin-binding site (methionine-lysine-methionine or methionine-lysine-leucine). The deduced protein sequence contains a putative transit peptide whose function was confirmed by its ability to direct in vitro chloroplast uptake. The subcellular localization of this biotin carboxylase has also been confirmed to be plastidial by western blot analysis of pea (Pisum sativum), alfalfa (Medicago sativa L.), and castor (Ricinus communis L.) plastid preparations. Northern blot analysis indicates that the plastid biotin carboxylase transcripts are expressed at severalfold higher levels in castor seeds than in leaves. PMID:7610168

Adenosylcobinamide methyl phosphate as a pseudocoenzyme for diol dehydrase.

PubMed

Ishida, A; Toraya, T

1993-02-16

Adenosylcobinamide methyl phosphate, a novel analog of adenosylcobalamin lacking the nucleotide loop moiety, was synthesized. It did not show detectable coenzymic activity but behaved as a strong competitive inhibitor against AdoCbl with relatively high affinity (Ki = 2.5 microM). When apoenzyme was incubated at 37 degrees C with this analog in the presence of substrate, the Co-C bond of the analog was almost completely and irreversibly cleaved within 10 min, forming an enzyme-bound Co(II)-containing species. The cleavage was not observed in the absence of substrate. The Co-C bond cleavage in the presence of substrate was not catalytic but stoichiometric, implying that the Co-C bond of the analog undergoes activation when the analog binds to the active site of the enzyme. 5'-Deoxyadenosine was the only product derived from the adenosyl group of the analog upon the Co-C bond cleavage. Apoenzyme did not undergo modification during this process. Therefore, it seems likely that adenosylcobinamide methyl phosphate acts as a pseudocoenzyme or a potent suicide coenzyme. Since adenosylcobinamide neither functions as coenzyme nor binds tightly to apoenzyme, it can be concluded that the phosphodiester moiety of the nucleotide loop of adenosylcobalamin is essential for tight binding to apoenzyme and therefore for subsequent activation of the Co-C bond and catalysis. It is also evident that the nucleotide loop is obligatory for the normal progress of catalytic cycle.

Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes

PubMed Central

Çelik, Burak; Sağıroğlu, Ali Asram; Özdemir, Samet

2017-01-01

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule found naturally in many eukaryotic cells and is essential for electron transport chain and energy generation in mitochondria. D-Panthenyl triacetate (PTA) is an oil-soluble derivative of D-panthenol, which is essential for coenzyme A synthesis in the epithelium. Liposomal formulations that encapsulate both ingredients were prepared and optimized by applying response surface methodology for increased stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10, 4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found to be 90.89%±3.61% and 87.84%±4.61%, respectively. Narrow size distribution was achieved with an average size of 161.6±3.6 nm, while a spherical and uniform shape was confirmed via scanning electron microscopy and transmission electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for CoQ10 was achieved after 24 hours of in vitro release study in sink conditions. Physical stability tests indicated that the optimized liposomes were suitable for storage at 4°C for at least 60 days. The results suggest that the optimized liposomal formulation would be a promising delivery system for both ingredients in various topical applications. PMID:28744121

Antimicrobial Peptides from Marine Proteobacteria

PubMed Central

Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

2013-01-01

After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

Isolation and characterization of cDNAs encoding wheat 3-hydroxy-3-methylglutaryl coenzyme A reductase.

PubMed Central

Aoyagi, K; Beyou, A; Moon, K; Fang, L; Ulrich, T

1993-01-01

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, EC 1.1.1.34) is a key enzyme in the isoprenoid biosynthetic pathway. We have isolated partial cDNAs from wheat (Triticum aestivum) using the polymerase chain reaction. Comparison of deduced amino acid sequences of these cDNAs shows that they represent a small family of genes that share a high degree of sequence homology among themselves as well as among genes from other organisms including tomato, Arabidopsis, hamster, human, Drosophila, and yeast. Southern blot analysis reveals the presence of at least four genes. Our results concerning the tissue-specific expression as well as developmental regulation of these HMGR cDNAs highlight the important role of this enzyme in the growth and development of wheat. PMID:8108513

Nicotinic Acid Metabolism, V. A Cobamide Coenzyme-Dependent Conversion of α-Methyleneglutaric Acid to Dimethylmaleic Acid

PubMed Central

Kung, H. F.; Cederbaum, S.; Tsai, L.; Stadtman, T. C.

1970-01-01

A new B12-coenzyme-dependent isomerization, catalyzed by extracts of a nicotinate-fermenting clostridium, results in the conversion of α-methyleneglutaric acid to dimethylmaleic acid. These two acids are intermediates in the multistep anaerobic process wherein nicotinate is converted, ultimately, to one mole each of propionate, acetate, carbon dioxide, and ammonia. Dimethylmaleic acid reacts in its anhydride form with 2,4-dinitrophenylhydrazine to form N-2′,4′-dinitrophenyl-anilino-3,4-dimethylmaleimide. The characteristic reddish color exhibited by the latter derivative in alkaline solution serves as a convenient quantitative assay for dimethylmaleic acid. Comparison of the 2,4-dinitrophenylhydrazine derivatives of the product of the enzymic reaction and of synthetic dimethylmaleic anhydride showed them to be identical in every respect. PMID:5266166

Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.

PubMed

Stefely, Jonathan A; Pagliarini, David J

2017-10-01

Coenzyme Q (CoQ, ubiquinone) is a redox-active lipid produced across all domains of life that functions in electron transport and oxidative phosphorylation and whose deficiency causes human diseases. Yet, CoQ biosynthesis has not been fully defined in any organism. Several proteins with unclear molecular functions facilitate CoQ biosynthesis through unknown means, and multiple steps in the pathway are catalyzed by currently unidentified enzymes. Here we highlight recent progress toward filling these knowledge gaps through both traditional biochemistry and cutting-edge 'omics' approaches. To help fill the remaining gaps, we present questions framed by the recently discovered CoQ biosynthetic complex and by putative biophysical barriers. Mapping CoQ biosynthesis, metabolism, and transport pathways has great potential to enhance treatment of numerous human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

PubMed

Malgoyre, Alexandra; Chabert, Clovis; Tonini, Julia; Koulmann, Nathalie; Bigard, Xavier; Sanchez, Hervé

2017-03-01

We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism. Therefore, we used a group of pair-fed rats (reproducing the same caloric restriction, as observed in hypoxic animals), in addition to the normoxic control fed ad libitum. The resting respiratory exchange ratio decreased after 21 days of exposure to hypobaric hypoxia (simulated elevation of 5,500 m). The respiration supported by pyruvate and octanoate were unaffected. In contrast, the maximal oxidative respiratory rate for PCoA, the transport of which depends on carnitine palmitoyltransferase 1 (CPT-1), decreased in the rapid-glycolytic EDL and increased in the slow-oxidative SOL, although hypoxia improved affinity for this substrate in both muscle types. PC and PCoA were oxidized similarly in normoxic EDL, whereas chronic hypoxia limited transport at the CPT-1 step in this muscle. The effects of hypoxia were mediated by caloric restriction in the SOL and by hypoxia itself in the EDL. We conclude that improvements in mitochondrial affinity for PCoA, a physiological long-chain fatty acid, would facilitate fatty-acid use at rest after chronic hypoxia independently of quantitative alterations of mitochondria. Conversely, decreasing the maximal oxidation of PCoA in fast-glycolytic muscles would limit fatty-acid use during exercise. NEW & NOTEWORTHY Affinity for low concentrations of long-chain fatty acids (LCFA) in mitochondria skeletal muscles increases after chronic hypoxia. Combined with a lower respiratory exchange ratio, this suggests facility for fatty acid utilization at rest. This fuel preference is related to caloric restriction in oxidative muscle and to hypoxia in glycolytic one. In contrast, maximal oxidation for LCFA is decreased by chronic hypoxia in glycolytic muscle and can explain glucose dependence at exercise. Copyright © 2017 the American Physiological Society.

Health-promoting ingredients from four selected Azorean macroalgae.

PubMed

Paiva, Lisete; Lima, Elisabete; Neto, Ana Isabel; Marcone, Massimo; Baptista, José

2016-11-01

This study presents, for the first time, the nutritional and health promoting aspects of four selected Azorean macroalgae (Ulva compressa, Ulva rigida, Gelidium microdon and Pterocladiella capillacea) in terms of total lipids, fatty acids (FA) profile, n6/n3 and hypocholesterolemic (h)/hypercholesterolemic (H) FA ratios, minerals, total essential amino acids (AA), anti-ageing and anti-phenylketonuria AA content, coenzyme Q 10 , α-tocopherol, total phenolics, antioxidant properties and energy value, on a dry weight basis. The results revealed low lipid content (1.02-4.32%) but significant PUFA content (29.57-69.22% of total FA), suitable FA ratios (0.48-9.49 for n6/n3 and 1.26-4.22 for h/H), balanced macromineral ratios (0.27-1.91 for Na/K and 0.15-1.07 for Ca/Mg), appreciable amount of essential AA (45.27-58.13% of total AA), high amount of anti-ageing AA, low Phe content, coenzyme Q 10 (1.25-8.27μg/g), α-tocopherol (2.61-9.14mg/100g), high total phenolic content (27.70-55.07mg of gallic acid equivalents/g extract), significant free radical scavenging activity (29.32-47.73%) and valuable energy content (6.80-9.80kJ/g). A regular consumption of these algae either directly or through food supplements may improve human health or may have a protective effect on some diseases and ageing process. They can also be used for producing pharmaceuticals and cosmeceuticals with potential economic value. Copyright © 2016. Published by Elsevier Ltd.

Overexpression of a BAHD Acyltransferase, OsAt10, Alters Rice Cell Wall Hydroxycinnamic Acid Content and Saccharification1[C][W][OA

PubMed Central

Bartley, Laura E.; Peck, Matthew L.; Kim, Sung-Ryul; Ebert, Berit; Manisseri, Chithra; Chiniquy, Dawn M.; Sykes, Robert; Gao, Lingfang; Rautengarten, Carsten; Vega-Sánchez, Miguel E.; Benke, Peter I.; Canlas, Patrick E.; Cao, Peijian; Brewer, Susan; Lin, Fan; Smith, Whitney L.; Zhang, Xiaohan; Keasling, Jay D.; Jentoff, Rolf E.; Foster, Steven B.; Zhou, Jizhong; Ziebell, Angela; An, Gynheung; Scheller, Henrik V.; Ronald, Pamela C.

2013-01-01

Grass cell wall properties influence food, feed, and biofuel feedstock usage efficiency. The glucuronoarabinoxylan of grass cell walls is esterified with the phenylpropanoid-derived hydroxycinnamic acids ferulic acid (FA) and para-coumaric acid (p-CA). Feruloyl esters undergo oxidative coupling with neighboring phenylpropanoids on glucuronoarabinoxylan and lignin. Examination of rice (Oryza sativa) mutants in a grass-expanded and -diverged clade of BAHD acyl-coenzyme A-utilizing transferases identified four mutants with altered cell wall FA or p-CA contents. Here, we report on the effects of overexpressing one of these genes, OsAt10 (LOC_Os06g39390), in rice. An activation-tagged line, OsAT10-D1, shows a 60% reduction in matrix polysaccharide-bound FA and an approximately 300% increase in p-CA in young leaf tissue but no discernible phenotypic alterations in vegetative development, lignin content, or lignin composition. Two additional independent OsAt10 overexpression lines show similar changes in FA and p-CA content. Cell wall fractionation and liquid chromatography-mass spectrometry experiments isolate the cell wall alterations in the mutant to ester conjugates of a five-carbon sugar with p-CA and FA. These results suggest that OsAT10 is a p-coumaroyl coenzyme A transferase involved in glucuronoarabinoxylan modification. Biomass from OsAT10-D1 exhibits a 20% to 40% increase in saccharification yield depending on the assay. Thus, OsAt10 is an attractive target for improving grass cell wall quality for fuel and animal feed. PMID:23391577

The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation

PubMed Central

Moncayo, Roy; Moncayo, Helga

2014-01-01

Background The aim of this study was to discern whether a relation between biochemical parameters, sonography and musculoskeletal data exists in cases of hyperthyroidism and whether they are modifiable through supplementation with selenomethionine and magnesium citrate as well as by acupuncture and manual medicine methods. Results A direct correlation between whole blood selenium and serum magnesium was found in subjects without thyroid disease and in menopausal women while it was reversed in cases of thyroid diseases as well as in patients with depression, infection, and in infertile women. Vascularization indices were elevated in cases of newly diagnosed benign thyroid diseases. Musculoskeletal changes i.e. lateral tension and idiopathic moving toes, as well as situations of physical and psychological stress and minor trauma and infection led to an increase of vascularization. Magnesium levels correlated negatively with these two conditions. The supplementation brought a reduction of the vascularization indices and reduced the incidence of idiopathic moving toes. Treatment of lateral tension required manual medicine methods and acupuncture (gastrocnemius). A small subgroup of patients showed a further reduction of hyper-vascularization after receiving coenzyme Q10. Conclusions We interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10. PMID:26675817

Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR alpha expression in adipose tissue.

PubMed

Hontecillas, Raquel; Diguardo, Maggie; Duran, Elisa; Orpi, Marcel; Bassaganya-Riera, Josep

2008-10-01

Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. We found that dietary CAT (1g/100g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) alpha and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels. CAT decreased abdominal fat deposition, increased HDL cholesterol, decreased TG concentrations, decreased glucose and insulin homeostasis and modulated WAT gene expression in a manner reminiscent of the actions of the PPAR alpha-activating fibrate class of lipid-lowering drugs.

A novel selection signature in stearoyl-coenzyme A desaturase (SCD) gene for enhanced milk fat content in Bubalus bubalis.

PubMed

Maryam, J; Babar, M E; Bao, Zhang; Nadeem, A

2016-10-01

Modern molecular interventions are dynamic gears for breeding animals with superior genetic make-up. These scientific efforts lead us toward sustainable dairy herds with improved milk production in terms of yield and quality. Many of candidate genes have been dissected at molecular level, and suitable genetic markers have been identified in cattle, but this work has not been validated in buffaloes so far. Stearoyl-coenzyme A desaturase (SCD) has been a potential candidate gene for fat content of milk. Genomic analysis of SCD revealed a total of six variations that were identified through DNA sequencing of animals with lower and higher butter fat %age. After statistical analysis, genotype AB of p.K158I could be associated (P value <0.0001) with higher milk fat %age (10.5 ± 0.5464). This SNP was validated on larger data set by cleaved amplified polymorphic sequences (CAPS) by using DdeI. To scrutinize the functional consequences of p.K158I, 3D protein structure of SCD was predicted by homology modeling and this variation was found located in the vicinity of functional domain and a part of transmembrane helix of this membrane integrated protein. This is a first report toward genetic screening of SCD gene at molecular level in buffalo. This report illustrates the implication of SCD gene and in particular p.K158I variation, in imparting its effect on milk fat %age, which can be targeted in selection of superior dairy buffaloes.

[Modulation of oxidative stresses in human aging skin].

PubMed

Blatt, T; Mundt, C; Mummert, C; Maksiuk, T; Wolber, R; Keyhani, R; Schreiner, V; Hoppe, U; Schachtschabel, D O; Stäb, F

1999-04-01

Oxidative stress (UV irradiation, free radicals) plays a significant role in aging. Coenzyme Q10 (CoQ10) and exogenously applied antioxidants can significantly reduce the formation of oxidative stress with increasing age. In our in vitro and in vivo experiments concerning the parameters of ultraweak photon emission (UPE), intracellular thiol status, mitochondrial membrane potential and cell vitality, we demonstrated a diminished resistance in keratinocytes of old donors against UV irradiation. This reduced epidermal resistance against oxidative stressors, i.e. UV irradiation, can be improved by topical application of CoQ10 and antioxidants like alpha-glucosylrutin (15). Furthermore, our in vivo investigations show that wrinkles around the region of the eyes ("crow feet") could be reduced by long-term application of CoQ10.

Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder.

PubMed

Meyer, Jacob D; Ellingson, Laura D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

2016-11-01

Exercise acutely improves mood in major depressive disorder (MDD). However, it is unknown whether benefits differ depending on whether exercise intensity is self-selected or prescribed. This study aimed to compare psychological and biological responses to preferred and prescribed steady-state exercise intensities to a patient-selected preferred intensity. Female adults (N = 24, age = 38.6 ± 14.0 yr) diagnosed with MDD completed four 30-min sessions of cycling exercise at three prescribed intensities (RPE of 11, 13, and 15) and one session with a self-selected intensity (preferred). Order was randomized and counterbalanced. Depressed mood (DM) was evaluated before, 10 min, and 30 min postexercise using the Profile of Mood States. Serum brain-derived neurotrophic factor (BDNF) was measured before and within 10 min postexercise. Changes in BDNF and DM for the preferred session were compared with the following prescribed sessions: 1) performed at the most similar intensity (matched on RPE; closest) and 2) with the greatest improvement in DM (greatest). Compared with the preferred session, improvement in DM was significantly larger after the greatest session (30 min postexercise: -11.8 ± 7.4 vs -3.4 ± 4.8), and the BDNF response was significantly greater after the closest session (5.4 ± 6.9 vs -1.4 ± 9.8 ng·mL). Permitting patients to select their own exercise intensity did not maximize improvements in mood. Further, preferred intensity exercise was also associated with a smaller BDNF response. Overall, the results suggest that exercise undertaken to improve mood should be prescribed on an individual basis in MDD and not necessarily based on the patient's preferred intensity. Clinicians, psychologists, and other practitioners should consider providing clear exercise intensity recommendations for symptom management in depression rather than allowing patients to self-select their intensity.

Eco-Chem

ERIC Educational Resources Information Center

Campbell, J. A.

1976-01-01

Presents questions and answers pertaining to yeast fermentation, oxygen content of the air, nutritional requirements of hot water bacteria, the hydrolysis of acetyl coenzyme A, and the stratified distribution of life in the Black Sea. (MLH)

MeaA, a Putative Coenzyme B12-Dependent Mutase, Provides Methylmalonyl Coenzyme A for Monensin Biosynthesis in Streptomyces cinnamonensis

PubMed Central

Zhang, Weiwen; Reynolds, Kevin A.

2001-01-01

The ratio of the major monensin analogs produced by Streptomyces cinnamonensis is dependent upon the relative levels of the biosynthetic precursors methylmalonyl-coenzyme A (CoA) (monensin A and monensin B) and ethylmalonyl-CoA (monensin A). The meaA gene of this organism was cloned and sequenced and was shown to encode a putative 74-kDa protein with significant amino acid sequence identity to methylmalonyl-CoA mutase (MCM) (40%) and isobutyryl-CoA mutase (ICM) large subunit (36%) and small subunit (52%) from the same organism. The predicted C terminus of MeaA contains structural features highly conserved in all coenzyme B12-dependent mutases. Plasmid-based expression of meaA from the ermE∗ promoter in the S. cinnamonensis C730.1 strain resulted in a decreased ratio of monensin A to monensin B, from 1:1 to 1:3. Conversely, this ratio increased to 4:1 in a meaA mutant, S. cinnamonensis WM2 (generated from the C730.1 strain by insertional inactivation of meaA by using the erythromycin resistance gene). In both of these experiments, the overall monensin titers were not significantly affected. Monensin titers, however, did decrease over 90% in an S. cinnamonensis WD2 strain (an icm meaA mutant). Monensin titers in the WD2 strain were restored to at least wild-type levels by plasmid-based expression of the meaA gene or the Amycolatopsis mediterranei mutAB genes (encoding MCM). In contrast, growth of the WD2 strain in the presence of 0.8 M valine led only to a partial restoration (<25%) of monensin titers. These results demonstrate that the meaA gene product is significantly involved in methylmalonyl-CoA production in S. cinnamonensis and that under the tested conditions the presence of both MeaA and ICM is crucial for monensin production in the WD2 strain. These results also indicate that valine degradation, implicated in providing methylmalonyl-CoA precursors for many polyketide biosynthetic processes, does not do so to a significant degree for monensin biosynthesis in the WD2 mutant. PMID:11222607

Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in Seeds.

PubMed

Yurchenko, Olga; Singer, Stacy D; Nykiforuk, Cory L; Gidda, Satinder; Mullen, Robert T; Moloney, Maurice M; Weselake, Randall J

2014-06-01

Low-molecular mass (10 kD) cytosolic acyl-coenzyme A-binding protein (ACBP) has a substantial influence over fatty acid (FA) composition in oilseeds, possibly via an effect on the partitioning of acyl groups between elongation and desaturation pathways. Previously, we demonstrated that the expression of a Brassica napus ACBP (BnACBP) complementary DNA in the developing seeds of Arabidopsis (Arabidopsis thaliana) resulted in increased levels of polyunsaturated FAs at the expense of eicosenoic acid (20:1 cisΔ11 ) and saturated FAs in seed oil. In this study, we investigated whether alterations in the FA composition of seed oil at maturity were correlated with changes in the acyl-coenzyme A (CoA) pool in developing seeds of transgenic Arabidopsis expressing BnACBP. Our results indicated that both the acyl-CoA pool and seed oil of transgenic Arabidopsis lines expressing cytosolic BnACBP exhibited relative increases in linoleic acid (18:2 cisΔ9,12 ; 17.9%-44.4% and 7%-13.2%, respectively) and decreases in 20:1 cisΔ11 (38.7%-60.7% and 13.8%-16.3%, respectively). However, alterations in the FA composition of the acyl-CoA pool did not always correlate with those seen in the seed oil. In addition, we found that targeting of BnACBP to the endoplasmic reticulum resulted in FA compositional changes that were similar to those seen in lines expressing cytosolic BnACBP, with the most prominent exception being a relative reduction in α-linolenic acid (18:3 cisΔ9,12,15 ) in both the acyl-CoA pool and seed oil of the former (48.4%-48.9% and 5.3%-10.4%, respectively). Overall, these data support the role of ACBP in acyl trafficking in developing seeds and validate its use as a biotechnological tool for modifying the FA composition of seed oil. © 2014 American Society of Plant Biologists. All Rights Reserved.

Effectiveness of Japanese SHARE model in improving Taiwanese healthcare personnel's preference for cancer truth telling.

PubMed

Tang, Woung-Ru; Chen, Kuan-Yu; Hsu, Sheng-Hui; Juang, Yeong-Yuh; Chiu, Shin-Che; Hsiao, Shu-Chun; Fujimori, Maiko; Fang, Chun-Kai

2014-03-01

Communication skills training (CST) based on the Japanese SHARE model of family-centered truth telling in Asian countries has been adopted in Taiwan. However, its effectiveness in Taiwan has only been preliminarily verified. This study aimed to test the effect of SHARE model-centered CST on Taiwanese healthcare providers' truth-telling preference, to determine the effect size, and to compare the effect of 1-day and 2-day CST programs on participants' truth-telling preference. For this one-group, pretest-posttest study, 10 CST programs were conducted from August 2010 to November 2011 under certified facilitators and with standard patients. Participants (257 healthcare personnel from northern, central, southern, and eastern Taiwan) chose the 1-day (n = 94) or 2-day (n = 163) CST program as convenient. Participants' self-reported truth-telling preference was measured before and immediately after CST programs, with CST program assessment afterward. The CST programs significantly improved healthcare personnel's truth-telling preference (mean pretest and posttest scores ± standard deviation (SD): 263.8 ± 27.0 vs. 281.8 ± 22.9, p < 0.001). The CST programs effected a significant, large (d = 0.91) improvement in overall truth-telling preference and significantly improved method of disclosure, emotional support, and additional information (p < 0.001). Participation in 1-day or 2-day CST programs did not significantly affect participants' truth-telling preference (p > 0.05) except for the setting subscale. Most participants were satisfied with the CST programs (93.8%) and were willing to recommend them to colleagues (98.5%). The SHARE model-centered CST programs significantly improved Taiwanese healthcare personnel's truth-telling preference. Future studies should objectively assess participants' truth-telling preference, for example, by cancer patients, their families, and other medical team personnel and at longer times after CST programs. Copyright © 2013 John Wiley & Sons, Ltd.

An exploration of parents' preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment.

PubMed

Hendry, Gordon J; Turner, Debbie E; Gardner-Medwin, Janet; Lorgelly, Paula K; Woodburn, James

2014-02-06

An increased awareness of patients' and parents' care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents' preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA). A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents' monetary valuation of health and service improvements. Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents' preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents' estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05. In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents' preferences.

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

PubMed Central

2014-01-01

Background An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA). Methods A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements. Results Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05. Conclusions In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences. PMID:24502508

Coenzyme Q10: Can It Prevent Statin Side Effects?

MedlinePlus

... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not ...

Does Patient Preference Measurement in Decision Aids Improve Decisional Conflict? A Randomized Trial in Men with Prostate Cancer.

PubMed

Shirk, Joseph D; Crespi, Catherine M; Saucedo, Josemanuel D; Lambrechts, Sylvia; Dahan, Ely; Kaplan, Robert; Saigal, Christopher

2017-12-01

Shared decision making (SDM) has been advocated as an approach to medical decision making that can improve decisional quality. Decision aids are tools that facilitate SDM in the context of limited physician time; however, many decision aids do not incorporate preference measurement. We aim to understand whether adding preference measurement to a standard patient educational intervention improves decisional quality and is feasible in a busy clinical setting. Men with incident localized prostate cancer (n = 122) were recruited from the Greater Los Angeles Veterans Affairs (VA) Medical Center urology clinic, Olive View UCLA Medical Center, and Harbor UCLA Medical Center from January 2011 to May 2015 and randomized to education with a brochure about prostate cancer treatment or software-based preference assessment in addition to the brochure. Men undergoing preference assessment received a report detailing the relative strength of their preferences for treatment outcomes used in review with their doctor. Participants completed instruments measuring decisional conflict, knowledge, SDM, and patient satisfaction with care before and/or after their cancer consultation. Baseline knowledge scores were low (mean 62%). The baseline mean total score on the Decisional Conflict Scale was 2.3 (±0.9), signifying moderate decisional conflict. Men undergoing preference assessment had a significantly larger decrease in decisional conflict total score (p = 0.023) and the Perceived Effective Decision Making subscale (p = 0.003) post consult compared with those receiving education only. Improvements in satisfaction with care, SDM, and knowledge were similar between groups. Individual-level preference assessment is feasible in the clinic setting. Patients with prostate cancer who undergo preference assessment are more certain about their treatment decisions and report decreased levels of decisional conflict when making these decisions.

Singer Responses to Sound Fields with a Simulated Reflection

NASA Astrophysics Data System (ADS)

NOSON, D.; SATO, S.; SAKAI, H.; ANDO, Y.

2000-04-01

While numerous recent studies have reported results concerning improvements to stage acoustics for orchestral performers, the preferred acoustical conditions on performing stages for singers has received limited attention in the past 20 years. A series of acoustical modifications have been proposed for a Seattle church to improve the acoustics for both the listeners and the performing choir. An on-site preliminary study was made to determine what acoustical changes might be important to singers. During solo fast-tempo singing and duet singing, singer preference increased with simulated short-delay reflections. The results suggest a potential for new reflectors to produce noticeable improvement in the choir acoustics. Subsequently, a solo singer study was conducted to establish preferred range of time delays for a single-simulated reflection. When singing faster-tempo music, the consensus of preference is statistically significant and the preferred delay averages 20 ms, while with a slow-tempo piece, the singers were not consistent in their judgment of preference and a strong individual variability predominated in the pair-comparison tests. The results point the way for an examination of a wider range of time delays and music motifs to acquire a clearer picture of consensus and individual preference for time-delayed reflections.

Organic dairy farmers put more emphasis on production traits than conventional farmers.

PubMed

Slagboom, M; Kargo, M; Edwards, D; Sørensen, A C; Thomasen, J R; Hjortø, L

2016-12-01

The overall aim of this research was to characterize the preferences of Danish dairy farmers for improvements in breeding goal traits. The specific aims were (1) to investigate the presence of heterogeneity in farmers' preferences by means of cluster analysis, and (2) to associate these clusters with herd characteristics and production systems (organic or conventional). We established a web-based survey to characterize the preferences of farmers for improvements in 10 traits, by means of pairwise rankings. We also collected a considerable number of herd characteristics. Overall, 106 organic farmers and 290 conventional farmers answered the survey, all with Holstein cows. The most preferred trait improvement was cow fertility, and the least preferred was calving difficulty. By means of cluster analysis, we identified 4 distinct clusters of farmers and named them according to the trait improvements that were most preferred: Health and Fertility, Production and Udder Health, Survival, and Fertility and Production. Some herd characteristics differed between clusters; for example, farmers in the Survival cluster had twice the percentage of dead cows in their herds compared with the other clusters, and farmers that gave the highest ranking to cow and heifer fertility had the lowest conception rate in their herds. This finding suggests that farmers prefer to improve traits that are more problematic in their herd. The proportion of organic and conventional farmers also differed between clusters; we found a higher proportion of organic farmers in the production-based clusters. When we analyzed organic and conventional data separately, we found that organic farmers ranked production traits higher than conventional farmers. The herds of organic farmers had lower milk yields and lower disease incidences, which might explain the high ranking of milk production and the low ranking of disease traits. This study shows that heterogeneity exists in farmers' preferences for improvements in breeding goal traits, that organic and conventional farmers differ in their preferences, and that herd characteristics can be linked to different farmer clusters. The results of this study could be used for the future development of breeding goals in Danish Holstein cows and for the development of customized total merit indices based on farmer preferences. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Application of Physical Organic Chemistry to Biochemical Problems.

ERIC Educational Resources Information Center

Westheimer, Frank

1986-01-01

Presents the synthesis of the science of enzymology from application of the concepts of physical organic chemistry from a historical perspective. Summarizes enzyme and coenzyme mechanisms elucidated prior to 1963. (JM)

Chem Ed Compacts

ERIC Educational Resources Information Center

Wolf, Walter A., Ed.

1976-01-01

Presents three activities: (1) the investigation of the purity and stability of nicotinamide and flavin coenzymes; (2) desk-computer fitting of a two-exponential function; and (3) an interesting and inexpensive solubility product experiment for introductory chemistry. (RH)

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, H.; Ding, Y.; Bartlam, M.

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also reportmore » that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.« less

Structure of Glycerol Dehydratase Reactivase: A New Type of Molecular Chaperone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Der-Ing; Reiss, Lisa; Turner, Jr., Ivan

2010-03-08

The function of glycerol dehydratase (GDH) reactivase is to remove damaged coenzyme B{sub 12} from GDH that has suffered mechanism-based inactivation. The structure of GDH reactivase from Klebsiella pneumoniae was determined at 2.4 {angstrom} resolution by the single isomorphous replacement with anomalous signal (SIR/AS) method. Each tetramer contains two elongated 63 kDa {alpha} subunits and two globular 14 kDa {beta} subunits. The {alpha} subunit contains structural features resembling both GroEL and Hsp70 groups of chaperones, and it appears chaperone like in its interactions with ATP. The fold of the {beta} subunit resembles that of the {beta} subunit of glycerol dehydratase,more » except that it lacks some coenzyme B12 binding elements. A hypothesis for the reactivation mechanism of reactivase is proposed based on these structural features.« less

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

PubMed

He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.

PubMed

Meegalla, Rupalie L; Billheimer, Jeffrey T; Cheng, Dong

2002-11-01

Glucose and insulin are anabolic signals which upregulate the transcriptions of a series of lipogenic enzymes to convert excess carbohydrate into triglycerides for efficient energy storage. These enzymes include ATP-citrate lyase (ACL), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (G3PA). Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is important to synthesize fatty acids into triglycerides. Two DGATs from different gene families have recently been identified. In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA. Treatment of adipocytes with glucose and insulin together results in higher DGAT activity in the membrane than cells treated with either of the agents alone, indicating that glucose and insulin have additive effect on DGAT activation. In mice treated with fast/refeeding protocol, DGAT2 mRNA decreased upon fasting and was replenished upon refeeding in adipose tissue and liver. This pattern of change was not observed for DGAT1. Inasmuch as DGAT1 mRNA is less abundant in liver, we suggest that DGAT1 is more involved in fat absorption in the intestine and in basal level triglyceride synthesis in adipose tissue where it is more highly expressed. In contrast, DGAT2 is more likely to play important roles in assembly of de novo synthesized fatty acids into VLDL particles in the liver.

A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine.

PubMed

Moncayo, Roy; Moncayo, Helga

2017-06-01

Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy. Current biochemical evidence about the elements required to maintain thyroid function shows that these not only include dietary iodine but also magnesium, iron, selenium and coenzyme Q10. Iron is important for the synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process of iodine uptake; iodine has to be sufficiently present in the diet; selenium acts through selenoproteins to protect the thyroid cell during hormone synthesis and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As a consequence, good clinical practice requires additional biochemical information on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status. Since these elements are also important for the maintenance of reproductive function, we postulate that they constitute the connecting link between both endocrine systems.

Utilization of xylitol dehydrogenase in a combined microbial/enzymatic process for production of xylitol from D-glucose.

PubMed

Mayer, Gerhard; Kulbe, Klaus D; Nidetzky, Bernd

2002-01-01

The production of xylitol from D-glucose occurs through a three-step process in which D-arabitol and D-xylulose are formed as the first and second intermediate product, respectively, and both are obtained via microbial bioconversion reactions. Catalytic hydrogenation of D-xylulose yields xylitol; however, it is contaminated with D-arabitol. The aim of this study was to increase the stereoselectivity of the D-xylulose reduction step by using enzymatic catalysis. Recombinant xylitol dehydrogenase from the yeast Galactocandida mastotermitis was employed to catalyze xylitol formation from D-xylulose in an NADH-dependent reaction, and coenzyme regeneration was achieved by means of formate dehydrogenase-catalyzed oxidation of formate into carbon dioxide. The xylitol yield from D-xylulose was close to 100%. Optimal productivity was found for initial coenzyme concentrations of between 0.5 and 0.75 mM. In the presence of 0.30 M (45 g/L) D-xylulose and 2000 U/L of both dehydrogenases, exhaustive substrate turnover was achieved typically in a 4-h reaction time. The enzymes were recovered after the reaction in yields of approx 90% by means of ultrafiltration and could be reused for up to six cycles of D-xylulose reduction. The advantages of incorporating the enzyme-catalyzed step in a process for producing xylitol from D-glucose are discussed, and strategies for downstream processing are proposed by which the observed coenzyme turnover number of approx 600 could be increased significantly.

Volatile Ester Formation in Roses. Identification of an Acetyl-Coenzyme A. Geraniol/Citronellol Acetyltransferase in Developing Rose Petals1

PubMed Central

Shalit, Moshe; Guterman, Inna; Volpin, Hanne; Bar, Einat; Tamari, Tal; Menda, Naama; Adam, Zach; Zamir, Dani; Vainstein, Alexander; Weiss, David; Pichersky, Eran; Lewinsohn, Efraim

2003-01-01

The aroma of roses (Rosa hybrida) is due to more than 400 volatile compounds including terpenes, esters, and phenolic derivatives. 2-Phenylethyl acetate, cis-3-hexenyl acetate, geranyl acetate, and citronellyl acetate were identified as the main volatile esters emitted by the flowers of the scented rose var. “Fragrant Cloud.” Cell-free extracts of petals acetylated several alcohols, utilizing acetyl-coenzyme A, to produce the corresponding acetate esters. Screening for genes similar to known plant alcohol acetyltransferases in a rose expressed sequence tag database yielded a cDNA (RhAAT1) encoding a protein with high similarity to several members of the BAHD family of acyltransferases. This cDNA was functionally expressed in Escherichia coli, and its gene product displayed acetyl-coenzyme A:geraniol acetyltransferase enzymatic activity in vitro. The RhAAT1 protein accepted other alcohols such as citronellol and 1-octanol as substrates, but 2-phenylethyl alcohol and cis-3-hexen-1-ol were poor substrates, suggesting that additional acetyltransferases are present in rose petals. The RhAAT1 protein is a polypeptide of 458 amino acids, with a calculated molecular mass of 51.8 kD, pI of 5.45, and is active as a monomer. The RhAAT1 gene was expressed exclusively in floral tissue with maximum transcript levels occurring at stage 4 of flower development, where scent emission is at its peak. PMID:12692346

LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2

PubMed Central

Marques, João C.; Oh, Il Kyu; Ly, Daniel C.; Lamosa, Pedro; Ventura, M. Rita; Miller, Stephen T.; Xavier, Karina B.

2014-01-01

The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli, can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2–dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli, a pathway that can be used to quench AI-2 and control quorum-sensing–regulated bacterial behaviors. PMID:25225400

The effect of coenzyme Q10 included by γ-cyclodextrin on the growth of fission yeast studied by microscope Raman spectroscopy

NASA Astrophysics Data System (ADS)

Nishida, Tatsuro; Kaino, Tomohiro; Ikarashi, Ryo; Nakata, Daisuke; Terao, Keiji; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

2013-09-01

The inclusion complex of coenzyme Q10 (CoQ10) by γ-cyclodextrin (γ-CD), CoQ10-CD complex, was recently developed. The addition of the CoQ10-CD complex recovered the growth of a fission yeast mutant strain, Δdps1, which otherwise cannot grow well due to the lack of coenzyme Q producing ability. However, the oxygen consumption rate of this strain was not restored by the addition of the CoQ10-CD complex. The addition of two other anti-oxidative reagents, glutathione and ascorbic acid, also recovered the growth of the Δdps1 strain as well. These results indicated that the recovery of the growth of Δdps1 was brought about by the anti-oxidative property of CoQ10. The intensity of Raman spectra of Δdps1 at 1602 cm-1, which is prominently observed for the wild type of the fission yeast, was compared between before and after addition of the CoQ10-CD complex. The signal was very weakly observed for Δdps1 and did not increase in intensity by the addition of the CoQ10-CD complex. These results suggested the recovery of the growth of Δdps1 was brought about not by the restoration of respiration function of Δdps1 but by the anti-oxidative property of CoQ10 to result in the decrease in the oxidative stress.

One ancestor for two codes viewed from the perspective of two complementary modes of tRNA aminoacylation

PubMed Central

Rodin, Andrei S; Szathmáry, Eörs; Rodin, Sergei N

2009-01-01

Background The genetic code is brought into action by 20 aminoacyl-tRNA synthetases. These enzymes are evenly divided into two classes (I and II) that recognize tRNAs from the minor and major groove sides of the acceptor stem, respectively. We have reported recently that: (1) ribozymic precursors of the synthetases seem to have used the same two sterically mirror modes of tRNA recognition, (2) having these two modes might have helped in preventing erroneous aminoacylation of ancestral tRNAs with complementary anticodons, yet (3) the risk of confusion for the presumably earliest pairs of complementarily encoded amino acids had little to do with anticodons. Accordingly, in this communication we focus on the acceptor stem. Results Our main result is the emergence of a palindrome structure for the acceptor stem's common ancestor, reconstructed from the phylogenetic trees of Bacteria, Archaea and Eukarya. In parallel, for pairs of ancestral tRNAs with complementary anticodons, we present updated evidence of concerted complementarity of the second bases in the acceptor stems. These two results suggest that the first pairs of "complementary" amino acids that were engaged in primordial coding, such as Gly and Ala, could have avoided erroneous aminoacylation if and only if the acceptor stems of their adaptors were recognized from the same, major groove, side. The class II protein synthetases then inherited this "primary preference" from isofunctional ribozymes. Conclusion Taken together, our results support the hypothesis that the genetic code per se (the one associated with the anticodons) and the operational code of aminoacylation (associated with the acceptor) diverged from a common ancestor that probably began developing before translation. The primordial advantage of linking some amino acids (most likely glycine and alanine) to the ancestral acceptor stem may have been selective retention in a protocell surrounded by a leaky membrane for use in nucleotide and coenzyme synthesis. Such acceptor stems (as cofactors) thus transferred amino acids as groups for biosynthesis. Later, with the advent of an anticodon loop, some amino acids (such as aspartic acid, histidine, arginine) assumed a catalytic role while bound to such extended adaptors, in line with the original coding coenzyme handle (CCH) hypothesis. Reviewers This article was reviewed by Rob Knight, Juergen Brosius and Anthony Poole. PMID:19173731

Molecular evolution of multiple arylalkylamine N-acetyltransferase (AANAT) in fish.

PubMed

Zilberman-Peled, Bina; Bransburg-Zabary, Sharron; Klein, David C; Gothilf, Yoav

2011-01-01

Arylalkylamine N-acetyltransferase (AANAT) catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to arylalkylamines, including indolethylamines and phenylethylamines. Multiple aanats are present in teleost fish as a result of whole genome and gene duplications. Fish aanat1a and aanat2 paralogs display different patterns of tissue expression and encode proteins with different substrate preference: AANAT1a is expressed in the retina, and acetylates both indolethylamines and phenylethylamines; while AANAT2 is expressed in the pineal gland, and preferentially acetylates indolethylamines. The two enzymes are therefore thought to serve different roles. Here, the molecular changes that led to their specialization were studied by investigating the structure-function relationships of AANATs in the gilthead seabream (sb, Sperus aurata). Acetylation activity of reciprocal mutated enzymes pointed to specific residues that contribute to substrate specificity of the enzymes. Inhibition tests followed by complementary analyses of the predicted three-dimensional models of the enzymes, suggested that both phenylethylamines and indolethylamines bind to the catalytic pocket of both enzymes. These results suggest that substrate selectivity of AANAT1a and AANAT2 is determined by the positioning of the substrate within the catalytic pocket, and its accessibility to catalysis. This illustrates the evolutionary process by which enzymes encoded by duplicated genes acquire different activities and play different biological roles.

Cloning of a coconut endosperm cDNA encoding a 1-acyl-sn-glycerol-3-phosphate acyltransferase that accepts medium-chain-length substrates.

PubMed Central

Knutzon, D S; Lardizabal, K D; Nelsen, J S; Bleibaum, J L; Davies, H M; Metz, J G

1995-01-01

Immature coconut (Cocos nucifera) endosperm contains a 1-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) activity that shows a preference for medium-chain-length fatty acyl-coenzyme A substrates (H.M. Davies, D.J. Hawkins, J.S. Nelsen [1995] Phytochemistry 39:989-996). Beginning with solubilized membrane preparations, we have used chromatographic separations to identify a polypeptide with an apparent molecular mass of 29 kD, whose presence in various column fractions correlates with the acyltransferase activity detected in those same fractions. Amino acid sequence data obtained from several peptides generated from this protein were used to isolate a full-length clone from a coconut endosperm cDNA library. Clone pCGN5503 contains a 1325-bp cDNA insert with an open reading frame encoding a 308-amino acid protein with a calculated molecular mass of 34.8 kD. Comparison of the deduced amino acid sequence of pCGN5503 to sequences in the data banks revealed significant homology to other putative LPAAT sequences. Expression of the coconut cDNA in Escherichia coli conferred upon those cells a novel LPAAT activity whose substrate activity profile matched that of the coconut enzyme. PMID:8552723

Modeling organizational justice improvements in a pediatric health service : a discrete-choice conjoint experiment.

PubMed

Cunningham, Charles E; Kostrzewa, Linda; Rimas, Heather; Chen, Yvonne; Deal, Ken; Blatz, Susan; Bowman, Alida; Buchanan, Don H; Calvert, Randy; Jennings, Barbara

2013-01-01

Patients value health service teams that function effectively. Organizational justice is linked to the performance, health, and emotional adjustment of the members of these teams. We used a discrete-choice conjoint experiment to study the organizational justice improvement preferences of pediatric health service providers. Using themes from a focus group with 22 staff, we composed 14 four-level organizational justice improvement attributes. A sample of 652 staff (76 % return) completed 30 choice tasks, each presenting three hospitals defined by experimentally varying the attribute levels. Latent class analysis yielded three segments. Procedural justice attributes were more important to the Decision Sensitive segment, 50.6 % of the sample. They preferred to contribute to and understand how all decisions were made and expected management to act promptly on more staff suggestions. Interactional justice attributes were more important to the Conduct Sensitive segment (38.5 %). A universal code of respectful conduct, consequences encouraging respectful interaction, and management's response when staff disagreed with them were more important to this segment. Distributive justice attributes were more important to the Benefit Sensitive segment, 10.9 % of the sample. Simulations predicted that, while Decision Sensitive (74.9 %) participants preferred procedural justice improvements, Conduct (74.6 %) and Benefit Sensitive (50.3 %) participants preferred interactional justice improvements. Overall, 97.4 % of participants would prefer an approach combining procedural and interactional justice improvements. Efforts to create the health service environments that patients value need to be comprehensive enough to address the preferences of segments of staff who are sensitive to different dimensions of organizational justice.

Genetics Home Reference: malonyl-CoA decarboxylase deficiency

MedlinePlus

... decarboxylase malonic aciduria malonyl-coenzyme A decarboxylase deficiency MCD deficiency Related Information How are genetic conditions and ... Morrell JC, Wanders RJ, Matalon R, Gould SJ. MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA ...

76 FR 80872 - Dow AgroScience LLC; Availability of Petition, Plant Pest Risk Assessment, and Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

... the herbicide 2,4-D) and resistance to grass herbicides in the aryloxyphenoxypropionate acetyl...-D) and resistance to grass herbicides in the aryloxyphenoxypropionate acetyl coenzyme A carboxylase...

Establishing a Mathematical Equations and Improving the Production of L-tert-Leucine by Uniform Design and Regression Analysis.

PubMed

Jiang, Wei; Xu, Chao-Zhen; Jiang, Si-Zhi; Zhang, Tang-Duo; Wang, Shi-Zhen; Fang, Bai-Shan

2017-04-01

L-tert-Leucine (L-Tle) and its derivatives are extensively used as crucial building blocks for chiral auxiliaries, pharmaceutically active ingredients, and ligands. Combining with formate dehydrogenase (FDH) for regenerating the expensive coenzyme NADH, leucine dehydrogenase (LeuDH) is continually used for synthesizing L-Tle from α-keto acid. A multilevel factorial experimental design was executed for research of this system. In this work, an efficient optimization method for improving the productivity of L-Tle was developed. And the mathematical model between different fermentation conditions and L-Tle yield was also determined in the form of the equation by using uniform design and regression analysis. The multivariate regression equation was conveniently implemented in water, with a space time yield of 505.9 g L -1  day -1 and an enantiomeric excess value of >99 %. These results demonstrated that this method might become an ideal protocol for industrial production of chiral compounds and unnatural amino acids such as chiral drug intermediates.

Vitamin B supplementation for diabetic peripheral neuropathy.

PubMed

Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

[MITOCHONDRIAL DYSFUNCTION: MODERN ASPECTS OF THERAPY (REVIEW)].

PubMed

Arveladze, G; Geladze, N; Khachapuridze, N; Bakhtadze, S; Kapanadze, N

2015-01-01

Mitochondrial diseases are considered as one of the major problems of modern interdisciplinary neonatology and pediatrics. Mitochondrial pathology can be revealed as refractory myoclonic or multifocal seizures, craniofacial dysostosis, dysmetabolic manifestations and respiratory disorders. Central nervous system (CNS), muscles, heart, liver and kidneys is involved in this pathological process. An important criterion for diagnosis of mitochondrial dysfunction is increases in blood lactate and pyruvate levels; the absolute criterion - molecular genetic diagnostic studies of mitochondrial DNA. Polymorphism of clinical symptoms complicates the process of early diagnostics, the lack clear recommendations complicates therapy. Modern aspects of treatment of mitochondrial dysfunction in various neurological syndromes are based primarily in improving the efficiency of the processes of oxidative phosphorylation at the system level. Dietary carbohydrate restriction, and medication (Coenzyme Q10, Idebenonum, Cofactors, drugs which reduce lactic acidosis- Dimephosphon, Dichloroacetate, Antioxidants, Anticonvulsants and Antidiabetic agents, vitamins C, E, K, hemotransfusions) is prescribed. Such complex approach allows us to achieve a reduction in lactate-acidosis, and improve the condition of patients in 70% of cases.

Factors affecting family satisfaction with inpatient end-of-life care.

PubMed

Sadler, Erin; Hales, Brigette; Henry, Blair; Xiong, Wei; Myers, Jeff; Wynnychuk, Lesia; Taggar, Ru; Heyland, Daren; Fowler, Robert

2014-01-01

Little data exists addressing satisfaction with end-of-life care among hospitalized patients, as they and their family members are systematically excluded from routine satisfaction surveys. It is imperative that we closely examine patient and institution factors associated with quality end-of-life care and determine high-priority target areas for quality improvement. Between September 1, 2010 and January 1, 2012 the Canadian Health care Evaluation Project (CANHELP) Bereavement Questionnaire was mailed to the next-of-kin of recently deceased inpatients to seek factors associated with satisfaction with end-of-life care. The primary outcome was the global rating of satisfaction. Secondary outcomes included rates of actual versus preferred location of death, associations between demographic factors and global satisfaction, and identification of targets for quality improvement. Response rate was 33% among 275 valid addresses. Overall, 67.4% of respondents were very or completely satisfied with the overall quality of care their relative received. However, 71.4% of respondents who thought their relative did not die in their preferred location favoured an out-of-hospital location of death. A common location of death was the intensive care unit (45.7%); however, this was not the preferred location of death for 47.6% of such patients. Multivariate Poisson regression analysis showed respondents who believed their relative died in their preferred location were 1.7 times more likely to be satisfied with the end-of-life care that was provided (p = 0.001). Items identified as high-priority targets for improvement included: relationships with, and characteristics of health care professionals; illness management; communication; and end-of-life decision-making. Nearly three-quarters of recently deceased inpatients would have preferred an out-of-hospital death. Intensive care units were a common, but not preferred, location of in-hospital deaths. Family satisfaction with end-of-life care was strongly associated with their relative dying in their preferred location. Improved communication regarding end-of-life care preferences should be a high-priority quality improvement target.

Effect of N-benzoyl-d-phenylalanine on lipid profile in liver of neonatal streptozotocin diabetic rats.

PubMed

Pari, Leelavinothan; Ashokkumar, Natarajan

2005-10-01

The effect of N-benzoyl-d-phenylalanine (NBDP) and metformin combination treatment on liver lipids and lipid peroxidation markers was studied in neonatal streptozotocin (nSTZ) diabetic rats. Oral administration of NBDP (50, 100 and 200 mg/kg body weight) and metformin (500 mg/kg body weight) for 6 weeks significantly reduced the elevated blood glucose, liver cholesterol, triglycerides, free fatty acids and phospholipids. The combination treatment also caused a significant decrease in hepatic hydroxymethyl glutaryl-coenzyme A reductase, Thiobarbituric Acid Reactive Substances (TBARS) and significant increase in reduced glutathione levels. The results show that NBDP and metformin improve the hepatic lipid profile and antioxidant status in nSTZ diabetic rats. Combination treatment was more effective than either drug alone.

Coenzyme Q10 for the treatment of heart failure: a review of the literature

PubMed Central

DiNicolantonio, James J; Bhutani, Jaikrit; McCarty, Mark F; O'Keefe, James H

2015-01-01

Coenzyme Q10 (CoQ10) is an endogenously synthesised and diet-supplied lipid-soluble cofactor that functions in the mitochondrial inner membrane to transfer electrons from complexes I and II to complex III. In addition, its redox activity enables CoQ10 to act as a membrane antioxidant. In patients with congestive heart failure, myocardial CoQ10 content tends to decline as the degree of heart failure worsens. A number of controlled pilot trials with supplemental CoQ10 in heart failure found improvements in functional parameters such as ejection fraction, stroke volume and cardiac output, without side effects. Subsequent meta-analyses have confirmed these findings, although the magnitude of benefit tends to be less notable in patients with severe heart failure, or within the context of ACE inhibitor therapy. The multicentre randomised placebo-controlled Q-SYMBIO trial has assessed the impact of supplemental CoQ10 on hard endpoints in heart failure. A total of 420 patients received either CoQ10 (100 mg three times daily) or placebo and were followed for 2 years. Although short-term functional endpoints were not statistically different in the two groups, CoQ10 significantly reduced the primary long-term endpoint—a major adverse cardiovascular event—which was observed in 15% of the treated participants compared to 26% of those receiving placebo (HR=0.50, CI 0.32 to 0.80, p=0.003). Particularly in light of the excellent tolerance and affordability of this natural physiological compound, supplemental CoQ10 has emerged as an attractive option in the management of heart failure, and merits evaluation in additional large studies. PMID:26512330

The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve.

PubMed

Gat, Itai; Blanco Mejia, Sonia; Balakier, Hanna; Librach, Clifford L; Claessens, Anne; Ryan, Edward A J

2016-07-01

The objective of this study is to compare the combination of dehydroepiandrosterone (DHEA) and coenzyme Q10 (CoQ10) (D + C) with DHEA alone (D) in intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles among patients with decreased ovarian reserve. We retrospectively extracted data from patients charts treated by DHEA with/without CoQ10 during IUI or IVF between February 2006 and June 2014. Prestimulation parameters included age, BMI, day 3 FSH and antral follicular count (AFC). Ovarian response parameters included total gonadotropins dosage, peak serum estradiol, number of follicles > 16 mm and fertilization rate. Clinical outcomes included clinical and ongoing pregnancy rates. Three hundred and thirty IUI cycles involved D + C compared with 467 cycles of D; 78 IVF cycles involved D + C and 175 D. In both IUI and IVF, AFC was higher with D + C compared with D (7.4 ± 5.7 versus 5.9 ± 4.7, 8.2 ± 6.3 versus 5.2 ± 5, respectively, p < 0.05). D + C resulted in a more follicles > 16 mm during IUI cycles (3.3 ± 2.3 versus 2.9 ± 2.2, respectively, p = 0.01), while lower mean total gonadotropin dosage was administered after D + C supplementation compared with D (3414 ± 1141 IUs versus 3877 ± 1143 IUs respectively, p = 0.032) in IVF cycles. Pregnancy and delivery rates were similar for both IUI and IVF. D + C significantly increases AFC and improves ovarian responsiveness during IUI and IVF without a difference in clinical outcome.

Analysis of Participant Withdrawal in Huntington Disease Clinical Trials.

PubMed

Banno, Haruhiko; Andrzejewski, Kelly L; McDermott, Michael P; Murphy, Alyssa; Majumder, Madhurima; de Blieck, Elisabeth A; Auinger, Peggy; Cudkowicz, Merit E; Atassi, Nazem

2017-01-01

Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials. We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal. Analyses of participant withdrawal were performed for three randomized, double-blind, placebo-controlled trials including the CARE-HD (coenzyme Q10 and remacemide in HD, n = 347), DOMINO (pilot study of minocycline in HD, n = 114), and 2CARE (coenzyme Q10 in HD, n = 609) trials. Reasons for withdrawal were obtained by review of textual data in the study databases. Participant demographic and clinical characteristics were analyzed as potential predictors of time to withdrawal using Cox-proportional hazards models. Estimated probabilities of withdrawal at 12 months were 2.9% for CARE-HD, 10.5% for DOMINO, and 5.9% for 2CARE. The top reasons for withdrawal (202 in total), expressed as mean percentage across the three trials, were loss to follow-up (23.2%), death (15.9%), and loss of interest/desire to participate (15.2%). Baseline and time-dependent variables associated with time to withdrawal were mainly motor, behavioral, and functional scores. Age, gender, ethnicity, and educational level were not associated with time to withdrawal in any of the three studies. The estimated withdrawal probability at 12 months ranged from 2.9% to 10.5% in the three HD trials considered here. A possible strategy to improve retention of participants in future HD clinical trials is to enroll individuals with higher baseline functional and behavioral status.

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul

2009-11-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibitedmore » increases in the transforming growth factor-beta1 (TGF-beta1) mRNA and alpha-smooth muscle actin (alpha-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of alpha-SMA and TGF-beta1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of alpha-SMA and TGF-beta1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-beta1 expression via Nrf2/ARE activation.« less

Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases.

PubMed

Zhang, Xun; Tohari, Ali Mohammad; Marcheggiani, Fabio; Zhou, Xinzhi; Reilly, James; Tiano, Luca; Shu, Xinhua

2017-01-01

Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration. The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed. CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions. A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

PubMed

Sanoobar, Meisam; Dehghan, Parvin; Khalili, Mohammad; Azimi, Amirreza; Seifar, Fatemeh

2016-01-01

Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS. We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms. A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P < 0.001, η(2) = 0.56) and BDI (baseline 17.8 ± 12.2 vs. endpoint 20.4 ± 11.4; F1,45 = 40.3, P < 0.001, η(2) = 0.48), indicating significant decrease of FSS and BDI in CoQ10 group compared to placebo group. Our study suggests that CoQ10 supplementation (500 mg/day) can improve fatigue and depression in patients with multiple sclerosis.

Protective effects of coenzyme Q10 nanoparticles on dichlorvos-induced hepatotoxicity and mitochondrial/lysosomal injury.

PubMed

Eftekhari, Aziz; Ahmadian, Elham; Azami, Aida; Johari-Ahar, Mohammad; Eghbal, Mohammad Ali

2018-02-01

Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In DDVP-treated and non-treated hepatocytes in the presence of CoQ10-NPs, cell viability, the level of reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, and cellular glutathione (GSH) content were measured. The prepared CoQ10-NPs were mono-dispersed and had narrow size distribution with average diameter of 54 nm. In the in vivo study, we evaluated the enzymes, which are involved in the antioxidant system for maintenance of normal liver function. In comparison to nonparticulate CoQ10, the CoQ10-NPs efficiently decreased the ROS formation, lipid peroxidation and cell death. Also, particulate form of CoQ10 improved MMP, GSH level and lysosome membrane integrity. In the in vivo, study, we revealed that CoQ10-NPs were better hepatoprotective than its nonparticulate form (P < .05). Altogether, we propose that the CoQ10-NPs have potential capability to be used as a therapeutic and prophylactic agent for poisoning that is induced by organophosphate agents, especially in the case of DDVP. Furthermore, these positive remarks make this nanoparticle amenable for the treatment of xenobiotic-induced liver diseases. © 2017 Wiley Periodicals, Inc.

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

PubMed

Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

Elimination of glycerol production in anaerobic cultures of a Saccharomyces cerevisiae strain engineered to use acetic acid as an electron acceptor.

PubMed

Guadalupe Medina, Víctor; Almering, Marinka J H; van Maris, Antonius J A; Pronk, Jack T

2010-01-01

In anaerobic cultures of wild-type Saccharomyces cerevisiae, glycerol production is essential to reoxidize NADH produced in biosynthetic processes. Consequently, glycerol is a major by-product during anaerobic production of ethanol by S. cerevisiae, the single largest fermentation process in industrial biotechnology. The present study investigates the possibility of completely eliminating glycerol production by engineering S. cerevisiae such that it can reoxidize NADH by the reduction of acetic acid to ethanol via NADH-dependent reactions. Acetic acid is available at significant amounts in lignocellulosic hydrolysates of agricultural residues. Consistent with earlier studies, deletion of the two genes encoding NAD-dependent glycerol-3-phosphate dehydrogenase (GPD1 and GPD2) led to elimination of glycerol production and an inability to grow anaerobically. However, when the E. coli mhpF gene, encoding the acetylating NAD-dependent acetaldehyde dehydrogenase (EC 1.2.1.10; acetaldehyde+NAD++coenzyme A<-->acetyl coenzyme A+NADH+H+), was expressed in the gpd1Delta gpd2Delta strain, anaerobic growth was restored by supplementation with 2.0 g liter(-1) acetic acid. The stoichiometry of acetate consumption and growth was consistent with the complete replacement of glycerol formation by acetate reduction to ethanol as the mechanism for NADH reoxidation. This study provides a proof of principle for the potential of this metabolic engineering strategy to improve ethanol yields, eliminate glycerol production, and partially convert acetate, which is a well-known inhibitor of yeast performance in lignocellulosic hydrolysates, to ethanol. Further research should address the kinetic aspects of acetate reduction and the effect of the elimination of glycerol production on cellular robustness (e.g., osmotolerance).

Antilipogenic and hypolipidemic effects of ethanol extracts from two variants of Artemisia princeps Pampanini in obese diabetic mice.

PubMed

Jung, Un Ju; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2009-12-01

The objective of this study was to determine the effects of the ethanol extract of two variants of Artemisia princeps Pampanini, Sajabalssuk (SB) and Sajuarissuk (SS), on lipid metabolism in type 2 diabetic animals. Male C57BL/KsJ-db/db mice were divided into control, SB ethanol extract (SBE) (0.171 g/100 g of diet), SS ethanol extract (SSE) (0.154 g/100 g of diet), and rosiglitazone (RG) (0.005 g/100 g of diet) groups. Supplementation of SBE and SSE significantly lowered the plasma levels of free fatty acid, triglyceride, and total cholesterol compared to the control group. The hepatic triglyceride and cholesterol contents and hepatic lipid droplets accumulation were also significantly lower in the SBE- and SSE-supplemented db/db mice than in the control or RG-supplemented db/db mice. Reductions of hepatic triglyceride and cholesterol contents in the SBE and SSE groups were related to the suppression of hepatic lipogenic enzyme activities, fatty acid synthesis (fatty acid synthase and malic enzyme), triglyceride synthesis (phosphatidate phosphohydrolase), and cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and esterification (acyl-coenzyme A:cholesterol acyltransferase). The RG supplement lowered plasma and hepatic lipid levels compared to the control group. However, RG significantly increased the white and brown adipose tissue weight and epididymal adipocyte size, whereas SBE and SSE lowered the brown adipose tissue weight and epididymal adipocyte size compared to the RG group. Together, these data suggest that supplementation of SBE and SSE partly improves lipid dysregulation and fatty liver in db/db mice by suppressing hepatic lipogenic enzyme activities.

Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women.

PubMed

Yubero-Serrano, Elena M; Delgado-Casado, Nieves; Delgado-Lista, Javier; Perez-Martinez, Pablo; Tasset-Cuevas, Inmaculada; Santos-Gonzalez, Monica; Caballero, Javier; Garcia-Rios, Antonio; Marin, Carmen; Gutierrez-Mariscal, Francisco M; Fuentes, Francisco; Villalba, Jose M; Tunez, Isaac; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2011-12-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.

Liquid chromatography-tandem mass spectrometry method for the measurement of serum mevalonic acid: a novel marker of hydroxymethylglutaryl coenzyme A reductase inhibition by statins.

PubMed

Waldron, Jenna; Webster, Craig

2011-05-01

Mevalonic acid (MVA) is synthesized at an early and rate-limiting step in the biosynthesis of cholesterol by the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, and is a useful measure of statin efficacy or treatment. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of serum MVA has been developed. Following the in vitro conversion of MVA to mevalonic acid lactone (MVAL) in the serum, MVAL and a deuterated internal standard were extracted using an online solid-phase extraction procedure. Chromatographic separation was achieved using a Luna PFP column (Phenomenex), with enhanced selectivity and improved resolution for polar compounds. A gradient system was used, with mobile phase comprising methanol and water (5 mmol/L ammonium formate buffer, pH 2.5). Analysis was performed using an API 5000 tandem mass spectrometer (Applied Biosystems) in positive electrospray ionization mode. The method showed excellent recoveries (98 ± 8%) and imprecision (intra-assay coefficient of variation of 2.2% [6.5 ng/mL] and 2.6% [10.5 ng/mL], and inter-assay coefficient of variation of 9% [10.5 ng/mL]). The assay provides a calibration range up to 50 ng/mL with a limit of detection at 0.1 ng/mL. A simple, rapid and analytically specific method has been developed for the measurement of serum MVA, in the form of MVAL. The high analytical sensitivity of the method allows for accurate quantitation of MVAL in serum samples, both at the endogenous levels found in healthy individuals and in statin-treated patients where normal levels are expected to be greatly reduced through the inhibition of HMG-CoA reductase.

Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver.

PubMed

Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

2014-10-15

Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. Copyright © 2014 Elsevier Inc. All rights reserved.

The lipid-lowering effect of dietary proanthocyanidins in rats involves both chylomicron-rich and VLDL-rich fractions.

PubMed

Quesada, Helena; Díaz, Sabina; Pajuelo, David; Fernández-Iglesias, Anabel; Garcia-Vallvé, Santiago; Pujadas, Gerard; Salvadó, M Josepa; Arola, Lluis; Bladé, Cinta

2012-07-01

Proanthocyanidins have been shown to improve postprandial hypertriacylglycerolaemia. The present study aims to determine the actual contribution of chylomicrons (CM) and VLDL in the hypotriacylglycerolaemic action of grape seed proanthocyanidin extract (GSPE) in the postprandial state and to characterise the mechanisms by which the GSPE treatment reduces TAG-rich lipoproteins in vivo. A plasma lipid tolerance test was performed on rats fasted for 14 h and orally loaded with lard containing either GSPE or not. GSPE (250 mg/kg body weight) markedly blocked the increase in plasma TAG induced by lard, with a statistically significant reduction of 22 % in the area under the curve. The VLDL-rich fraction was the major contributor (72 %) after 1 h, whereas the CM-rich fraction was the major contributor (85 %) after 3 h. At 5 and 7 h after treatment, CM-rich and VLDL-rich fractions showed a similar influence. Plasma post-heparin lipoprotein lipase (LPL) activity and LPL mRNA levels in white adipose tissue and muscle were not affected by GSPE. On the contrary, GSPE treatment significantly repressed (30 %) the secretion of VLDL-TAG. In the liver, GSPE treatment induced different effects on the expression of acyl-coenzyme A synthetase long-chain family member 1, Apoc3 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase at 1 h and Cd36 at 5 h, compared to those induced by lard. Furthermore, GSPE treatment significantly increased the activity of carnitine palmitoyltransferase 1a at 1 h. In conclusion, both CM-rich and VLDL-rich fractions contributed to the hypotriacylglycerolaemic action of GSPE, but their influence depended on time. GSPE induces hypotriacylglycerolaemic actions by repressing lipoprotein secretion and not by increasing LPL activity.

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

PubMed

Postorino, Elisa I; Rania, Laura; Aragona, Emanuela; Mannucci, Carmen; Alibrandi, Angela; Calapai, Gioacchino; Puzzolo, Domenico; Aragona, Pasquale

2018-01-01

Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Reduction of coenzyme q10 content: a possible effect of isoproterenol on heart failure and myocardial infarction in rat.

PubMed

Khorrami, A; Garjani, A; Ghanbarzadeh, S; Andalib, S

2014-04-01

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration. © Georg Thieme Verlag KG Stuttgart · New York.

The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wongnate, T.; Sliwa, D.; Ginovska, B.

2016-05-19

Methyl-coenzyme M reductase (MCR), the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the production of over one billion tons of methane per year. The mechanism of methane synthesis is unknown, with the two leading proposals involving either a methyl-nickel(III) (Mechanism I) or methyl radical/Ni(II)-thiolate (Mechanism II) intermediate(s). When the reaction between the active Ni(I) enzyme with substrates was studied by transient kinetic, spectroscopic and computational methods, formation of an EPR-silent Ni(II)-thiolate intermediate was positively identified by magnetic circular dichroism spectroscopy. There was no evidence for an EPR-active methyl-Ni(III) species. Temperature-dependent transient kinetic studies revealed that themore » activation energy for the initial catalytic step closely matched the value computed by density functional theory for Mechanism II. Thus, our results demonstrate that biological methane synthesis occurs by generation of a methyl radical.« less

Metabolic control of respiratory levels in coenzyme Q biosynthesis-deficient Escherichia coli strains leading to fine-tune aerobic lactate fermentation.

PubMed

Wu, Hui; Bennett, George N; San, Ka-Yiu

2015-08-01

A novel strategy to finely control the electron transfer chain (ETC) activity of Escherichia coli was established. In this study, the fine-tuning of the ubiquinone biosynthesis pathway was applied to further controlling ETC function in coenzyme Q8 biosynthesis-deficient E. coli strains, HW108 and HW109, which contain mutations in ubiE and ubiG, respectively. A competing pathway on the intermediate substrates of the Q8 synthesis pathway, catalyzed by diphosphate:4-hydroxybenzoate geranyltransferase (PGT-1) of Lithospermum erythrorhizon, was introduced into these mutant strains. A nearly theoretical yield of lactate production can be achieved under fully aerobic conditions via an in vivo, genetically fine-tunable means to further control the activity of the ETC of the Q8 biosynthesis-deficient E. coli strains. © 2015 Wiley Periodicals, Inc.

Biosynthesis of p-Hydroxybenzoate from p-Coumarate and p-Coumaroyl-Coenzyme A in Cell-Free Extracts of Lithospermum erythrorhizon Cell Cultures.

PubMed Central

Loscher, R.; Heide, L.

1994-01-01

The enzymatic formation of p-hydroxybenzoate from p-coumarate in cell-free extracts of cell cultures of Lithospermum erythrorhizon Sieb. et Zucc. was investigated. p-Coumaroyl-coenzyme A (p-coumaroyl-CoA) is the activated intermediate in this biosynthetic reaction. It is formed by an ATP-, Mg2+ -, and CoA-dependent 4-hydroxycinnamate:CoA ligase reaction. p-Coumaroyl-CoA is oxidized and cleaved to p-hydroxybenzoyl-CoA and acetyl-CoA in a thioclastic reaction in which NAD is an essential cofactor. These CoA esters are rapidly hydrolyzed to acetate and p-hydroxybenzoate, probably by thioesterases. The enzymes involved in the formation of p-hydroxybenzoate are soluble. p-Hydroxybenzalde-hyde is not an intermediate in this conversion, and S-denosylmethionine and uridine-5[prime]-diphosphoglucose do not enhance formation of p-hydroxybenzoate in our system. PMID:12232327

Factors affecting the palmitoyl-coenzyme A desaturase of Saccharomyces cerevisiae

NASA Technical Reports Server (NTRS)

Klein, H. P.; Volkmann, C. M.

1975-01-01

The activity and stability of the palmitoyl-coenzyme A (CoA) desaturase complex of Saccharomyces cerevisiae was influenced by several factors. Cells, grown nonaerobically and then incubated with glucose, either in air or under N2, showed a marked increase in desaturase activity. Cycloheximide, added during such incubations, prevented the increase in activity, suggesting de novo synthesis. The stability of the desaturase from cells grown nonaerobically was affected by subsequent treatment of the cells; enzyme from freshly harvested cells, or from cells that were then shaken under nitrogen, readily lost activity upon washing or during density gradient analysis, whereas aerated cells, in the presence or absence of glucose, yielded stable enzyme preparations. The loss of activity in nonaerobic preparations could be reversed by adding soluble supernatant from these homogenates and could be prevented by growing the cells in the presence of palmitoleic acid and ergosterol, but not with several other lipids tested.

Reductive, Coenzyme A-Mediated Pathway for 3-Chlorobenzoate Degradation in the Phototrophic Bacterium Rhodopseudomonas palustris

PubMed Central

Egland, Paul G.; Gibson, Jane; Harwood, Caroline S.

2001-01-01

We isolated a strain of Rhodopseudomonas palustris (RCB100) by selective enrichment in light on 3-chlorobenzoate to investigate the steps that it uses to accomplish anaerobic dechlorination. Analyses of metabolite pools as well as enzyme assays suggest that R. palustris grows on 3-chlorobenzoate by (i) converting it to 3-chlorobenzoyl coenzyme A (3-chlorobenzoyl–CoA), (ii) reductively dehalogenating 3-chlorobenzoyl–CoA to benzoyl-CoA, and (iii) degrading benzoyl-CoA to acetyl-CoA and carbon dioxide. R. palustris uses 3-chlorobenzoate only as a carbon source and thus incorporates the acetyl-CoA that is produced into cell material. The reductive dechlorination route used by R. palustris for 3-chlorobenzoate degradation differs from those previously described in that a CoA thioester, rather than an unmodified aromatic acid, is the substrate for complete dehalogenation. PMID:11229940

Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae

PubMed Central

Falcón, Alaric A.; Chen, Shaoping; Wood, Michael S.

2013-01-01

Acs2p is one of two acetyl-coenzyme A synthetases in Saccharomyces cerevisiae. We have prepared and characterized a monoclonal antibody specific for Acs2p and find that Acs2p is localized primarily to the nucleus, including the nucleolus, with a minor amount in the cytosol. We find that Acs2p is required for replicative longevity: an acs2Δ strain has a reduced replicative life span compared to wild-type and acs1Δ strains. Furthermore, replicatively aged acs2Δ cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2Δ strain. These findings indicate that Acs2p-mediated synthesis of acetyl-CoA in the nucleus functions to promote rDNA silencing and replicative longevity in yeast. PMID:19618123

Current state of coenzyme Q(10) production and its applications.

PubMed

Jeya, Marimuthu; Moon, Hee-Jung; Lee, Jeong-Lim; Kim, In-Won; Lee, Jung-Kul

2010-02-01

Coenzyme Q(10) (CoQ(10)), an obligatory cofactor in the aerobic respiratory electron transfer for energy generation, is formed from the conjugation of a benzoquinone ring with a hydrophobic isoprenoid chain. CoQ(10) is now used as a nutritional supplement because of its antioxidant properties and is beneficial in the treatment of several human diseases when administered orally. Bioprocesses have been developed for the commercial production of CoQ(10) because of its increased demand, and these bioprocesses depend on microbes that produce high levels of CoQ(10) naturally. However, as knowledge of the biosynthetic enzymes and the regulatory mechanisms modulating CoQ(10) production increases, approaches arise for the genetic engineering of CoQ(10) production in Escherichia coli and Agrobacterium tumefaciens. This review focused on approaches for CoQ(10) production, strategies used to engineer CoQ(10) production in microbes, and potential applications of CoQ(10).

Coenzyme Q(10) , endothelial function, and cardiovascular disease.

PubMed

Littarru, Gian Paolo; Tiano, Luca; Belardinelli, Romualdo; Watts, Gerald F

2011-01-01

Since the time a precise role of coenzyme Q(10) (CoQ(10) ) in myocardial bioenergetics was established, the involvement of CoQ in the pathophysiology of heart failure was hypothesized. This provided the rationale for numerous clinical trials of CoQ(10) as adjunctive treatment for heart failure. A mild hypotensive effect of CoQ was reported in the early years of clinical use of this compound. We review early human and animal studies on the vascular effects of CoQ. We then focus on endothelial dysfunction in type 2 diabetes and the possible impact on this condition of antioxidants and nutritional supplements, and in particular the therapeutic effects of CoQ. The effect of CoQ(10) on endothelial dysfunction in ischemic heart disease is also reviewed together with recent data highlighting that treatment with CoQ(10) increases extracellular SOD activity. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Acetate Utilization and Butyryl Coenzyme A (CoA):Acetate-CoA Transferase in Butyrate-Producing Bacteria from the Human Large Intestine

PubMed Central

Duncan, Sylvia H.; Barcenilla, Adela; Stewart, Colin S.; Pryde, Susan E.; Flint, Harry J.

2002-01-01

Seven strains of Roseburia sp., Faecalibacterium prausnitzii, and Coprococcus sp. from the human gut that produce high levels of butyric acid in vitro were studied with respect to key butyrate pathway enzymes and fermentation patterns. Strains of Roseburia sp. and F. prausnitzii possessed butyryl coenzyme A (CoA):acetate-CoA transferase and acetate kinase activities, but butyrate kinase activity was not detectable either in growing or in stationary-phase cultures. Although unable to use acetate as a sole source of energy, these strains showed net utilization of acetate during growth on glucose. In contrast, Coprococcus sp. strain L2-50 is a net producer of acetate and possessed detectable butyrate kinase, acetate kinase, and butyryl-CoA:acetate-CoA transferase activities. These results demonstrate that different functionally distinct groups of butyrate-producing bacteria are present in the human large intestine. PMID:12324374

Plasma levels of coenzyme Q10 in children with hyperthyroidism.

PubMed

Menke, Thomas; Niklowitz, Petra; Reinehr, Thomas; de Sousa, Gideon John; Andler, Werner

2004-01-01

In hyperthyroidism, increased oxygen consumption and free radical production in the stimulated respiratory chain leads to oxidative stress. Apart from its antioxidative function, coenzyme Q10 (CoQ10) is involved in electron transport in the respiratory chain. The aim of this study was to determine whether there is a correlation between an increased respiratory chain activity and the state of CoQ10 in children with hyperthyroidism. The CoQ10 plasma concentration was measured by high-performance liquid chromatography in 12 children with hyperthyroidism before and after treatment. In the hyperthyroid state, the plasma level of CoQ10 was significantly decreased in comparison with the level in the euthyroid state. The correction of the hyperthyroid state resulted in a normalization of the CoQ10 level. Plasma CoQ10 deficiency appears to be related to the stimulated respiratory chain activity in children with hyperthyroidism. Copyright 2004 S. Karger AG, Basel

Kinetic studies of the inhibition of a human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme by bile acids and anti-inflammatory drugs.

PubMed

Miyabe, Y; Amano, T; Deyashiki, Y; Hara, A; Tsukada, F

1995-01-01

We have investigated the steady-state kinetics for a cytosolic 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme of human liver and its inhibition by several bile acids and anti-inflammatory drugs such as indomethacin, flufemanic acid and naproxen. Initial velocity and product inhibition studies performed in the NADP(+)-linked (S)-1-indanol oxidation at pH 7.4 were consistent with a sequential ordered mechanism in which NADP+ binds first and leaves last. The bile acids and drugs, competitive inhibitors with respect to the alcohol substrate, exhibited uncompetitive inhibition with respect to the coenzyme, with Ki values less than 1 microM, whereas indomethacin exhibited noncompetitive inhibition (Ki < 24 microM). The kinetics of the inhibition by a mixture of the two inhibitors suggests that bile acids and drugs, except indomethacin, bind to overlapping sites at the active center of the enzyme-coenzyme binary complex.

Exome Sequence Reveals Mutations in CoA Synthase as a Cause of Neurodegeneration with Brain Iron Accumulation

PubMed Central

Dusi, Sabrina; Valletta, Lorella; Haack, Tobias B.; Tsuchiya, Yugo; Venco, Paola; Pasqualato, Sebastiano; Goffrini, Paola; Tigano, Marco; Demchenko, Nikita; Wieland, Thomas; Schwarzmayr, Thomas; Strom, Tim M.; Invernizzi, Federica; Garavaglia, Barbara; Gregory, Allison; Sanford, Lynn; Hamada, Jeffrey; Bettencourt, Conceição; Houlden, Henry; Chiapparini, Luisa; Zorzi, Giovanna; Kurian, Manju A.; Nardocci, Nardo; Prokisch, Holger; Hayflick, Susan; Gout, Ivan; Tiranti, Valeria

2014-01-01

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA. PMID:24360804

Home-based HIV testing for men preferred over clinic-based testing by pregnant women and their male partners, a nested cross-sectional study.

PubMed

Osoti, Alfred Onyango; John-Stewart, Grace; Kiarie, James Njogu; Barbra, Richardson; Kinuthia, John; Krakowiak, Daisy; Farquhar, Carey

2015-07-30

Male partner HIV testing and counseling (HTC) is associated with enhanced uptake of prevention of mother-to-child HIV transmission (PMTCT), yet male HTC during pregnancy remains low. Identifying settings preferred by pregnant women and their male partners may improve male involvement in PMTCT. Participants in a randomized clinical trial (NCT01620073) to improve male partner HTC were interviewed to determine whether the preferred male partner HTC setting was the home, antenatal care (ANC) clinic or VCT center. In this nested cross sectional study, responses were evaluated at baseline and after 6 weeks. Differences between the two time points were compared using McNemar's test and correlates of preference were determined using logistic regression. Among 300 pregnant female participants, 54% preferred home over ANC clinic testing (34.0%) or VCT center (12.0%). Among 188 male partners, 68% preferred home-based HTC to antenatal clinic (19%) or VCT (13%). Men who desired more children and women who had less than secondary education or daily income < $2 USD were more likely to prefer home-based over other settings (p < 0.05 for all comparisons). At 6 weeks, the majority of male (81%) and female (65%) participants recommended home over alternative HTC venues. Adjusting for whether or not the partner was tested during follow-up did not significantly alter preferences. Pregnant women and their male partners preferred home-based compared to clinic or VCT-center based male partner HTC. Home-based HTC during pregnancy appears acceptable and may improve male testing and involvement in PMTCT.

Patients Should Define Value in Health Care: A Conceptual Framework.

PubMed

Kamal, Robin N; Lindsay, Sarah E; Eppler, Sara L

2018-05-10

The main tenet of value-based health care is delivering high-quality care that is centered on the patient, improving health, and minimizing cost. Collaborative decision-making frameworks have been developed to help facilitate delivering care based on patient preferences (patient-centered care). The current value-based health care model, however, focuses on improving population health and overlooks the individuality of patients and their preferences for care. We highlight the importance of eliciting patient preferences in collaborative decision making and describe a conceptual framework that incorporates individual patients' preferences when defining value. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power Partitioning in Plant Stress and Development

PubMed Central

Li, Bin-Bin; Wang, Xiang; Tai, Li; Ma, Tian-Tian; Shalmani, Abdullah; Liu, Wen-Ting; Li, Wen-Qiang; Chen, Kun-Ming

2018-01-01

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormone metabolism and signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants. PMID:29662499

Putting together a plasma membrane NADH oxidase: a tale of three laboratories.

PubMed

Löw, Hans; Crane, Frederick L; Morré, D James

2012-11-01

The observation that high cellular concentrations of NADH were associated with low adenylate cyclase activity led to a search for the mechanism of the effect. Since cyclase is in the plasma membrane, we considered the membrane might have a site for NADH action, and that NADH might be oxidized at that site. A test for NADH oxidase showed very low activity, which could be increased by adding growth factors. The plasma membrane oxidase was not inhibited by inhibitors of mitochondrial NADH oxidase such as cyanide, rotenone or antimycin. Stimulation of the plasma membrane oxidase by iso-proterenol or triiodothyronine was different from lack of stimulation in endoplasmic reticulum. After 25 years of research, three components of a trans membrane NADH oxidase have been discovered. Flavoprotein NADH coenzyme Q reductases (NADH cytochrome b reductase) on the inside, coenzyme Q in the middle, and a coenzyme Q oxidase on the outside as a terminal oxidase. The external oxidase segment is a copper protein with unique properties in timekeeping, protein disulfide isomerase and endogenous NADH oxidase activity, which affords a mechanism for control of cell growth by the overall NADH oxidase and the remarkable inhibition of oxidase activity and growth of cancer cells by a wide range of anti-tumor drugs. A second trans plasma membrane electron transport system has been found in voltage dependent anion channel (VDAC), which has NADH ferricyanide reductase activity. This activity must be considered in relation to ferricyanide stimulation of growth and increased VDAC antibodies in patients with autism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cloning and expression of clostridium acetobutylicum ATCC 824 acetoacetyl-coenzyme A:acetate/butyrate:coenzyme A-transferase in Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cary, J.W.; Petersen, D.J.; Bennett, G.N.

1990-06-01

Coenzyme A (CoA)-transferase (acetoacetyl-CoA:acetate/butyrate:CoA-transferase (butyrate-acetoacetate CoA-transferase) (EC 2.8.3.9)) of Clostridium acetobutylicum ATCC 824 is an important enzyme in the metabolic shift between the acid-producing and solvent-forming states of this organism. The genes encoding the two subunits of this enzyme have been cloned and subsequent subcloning experiments established the position of the structural genes for CoA-transferase. Complementation of Escherichia coli ato mutants with the recombinant plasmid pCoAT4 (pUC19 carrying a 1.8-kilobase insert of C. acetobutylicum DNA encoding CoA-transferase activity) enabled the transformants to grow on butyrate as a sole carbon source. Despite the ability of CoA-transferase to complement the ato defectmore » in E. coli mutants, Southern blot and Western blot (immunoblot) analyses showed showed that neither the C. acetobutylicum genes encoding CoA-transferase nor the enzyme itself shared any apparent homology with its E. coli counterpart. Polypeptides of M{sub r} of the purified CoA-transferase subunits were observed by Western blot and maxicell analysis of whole-cell extracts of E.coli harboring pCoAT4. The proximity and orientation of the genes suggest that the genes encoding the two subunits of CoA-transferase may form an operon similar to that found in E. coli. In the plasmid, however, transcription appears to be primarily from the lac promoter of the vector.« less

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats

PubMed Central

Astolfi, Laura; Simoni, Edi; Valente, Filippo; Ghiselli, Sara; Hatzopoulos, Stavros; Chicca, Milvia; Martini, Alessandro

2016-01-01

Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter). The Cpt was administered intraperitoneally in a single dose (14 mg/kg) or in three daily doses (4.6 mg/kg/day) to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention. PMID:27632426

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binukumar, BK; Gupta, Nidhi; Bal, Amanjit

Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q{sub 10} (CoQ{sub 10}) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, {alpha}-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg bodymore » weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, {alpha}-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q{sub 10} (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q{sub 10} administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, {alpha}-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: > CoQ{sub 10} administration attenuates dichlorvos induced nigrostriatal neurodegenaration. > CoQ{sub 10} pre treatment leads to preservation of TH-IR neurons. > CoQ{sub 10} may decrease oxidative damage and {alpha}-synuclin aggregation. > CoQ{sub 10} treatment enhances motor function and protects rats from catalepsy.« less

Synthesis of fruity ethyl esters by acyl coenzyme A: alcohol acyltransferase and reverse esterase activities in Oenococcus oeni and Lactobacillus plantarum.

PubMed

Costello, P J; Siebert, T E; Solomon, M R; Bartowsky, E J

2013-03-01

To assess the abilities of commercial wine lactic acid bacteria (LAB) to synthesize potentially flavour active fatty acid ethyl esters and determine mechanisms involved in their production. Oenococcus oeni AWRI B551 produced significant levels of ethyl hexanoate and ethyl octanoate following growth in an ethanolic test medium, and ester formation generally increased with increasing pH (4.5 > 3.5), anaerobiosis and precursor supplementation. Cell-free extracts of commercial O. oeni strains and Lactobacillus plantarum AWRI B740 were also tested for ester-synthesizing capabilities in a phosphate buffer via: (i) acyl coenzyme A: alcohol acyltransferase (AcoAAAT) activity and (ii) reverse esterase activity. For both ester-synthesizing activities, strain-dependent variation was observed, with AcoAAAT activity generally greater than reverse esterase. Reverse esterase in O. oeni AWRI B551 also esterified 1-propanol to produce propyl octanoate, and deuterated substrates ([(2)H(6)]ethanol and [(2)H(15)]octanoic acid) to produce the fully deuterated ester, [(2)H(5)]ethyl [(2)H(15)]octanoate. Wine LAB exhibit ethyl ester-synthesizing capability and possess two different ester-synthesizing activities, one of which is associated with an acyl coenzyme A: alcohol acyltransferase. This study demonstrates that wine LAB exhibit enzyme activities that can augment the ethyl ester content of wine. This knowledge will facilitate greater control over the impacts of malolactic fermentation on the fruity sensory properties and quality of wine. © 2012 Australian Wine Research Institute © 2012 The Society for Applied Microbiology.

Production of stable isotope-labeled acyl-coenzyme A thioesters by yeast stable isotope labeling by essential nutrients in cell culture

PubMed Central

Snyder, Nathaniel W.; Tombline, Gregory; Worth, Andrew J.; Parry, Robert C.; Silvers, Jacob A.; Gillespie, Kevin P.; Basu, Sankha S.; Millen, Jonathan; Goldfarb, David S.; Blair, Ian A.

2015-01-01

Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and catabolic pathways, including fatty acid biosynthesis and β-oxidation, the Krebs cycle, and cholesterol and isoprenoid biosynthesis. Stable isotope dilution-based methodology is the gold standard for quantitative analyses by mass spectrometry. However, chemical synthesis of families of stable isotope labeled metabolites such as acyl-coenzyme A thioesters is impractical. Previously, we biosynthetically generated a library of stable isotope internal standard analogs of acyl-CoA thioesters by exploiting the essential requirement in mammals and insects for pantothenic acid (vitamin B5) as a metabolic precursor for the CoA backbone. By replacing pantothenic acid in the cell media with commercially available [13C3 15N1]-pantothenic acid, mammalian cells exclusively incorporated [13C3 15N1]-pantothenate into the biosynthesis of acyl-CoA and acyl-CoA thioesters. We have now developed a much more efficient method for generating stable isotope labeled CoA and acyl-CoAs from [13C3 15N1]-pantothenate using Stable Isotope Labeling by Essential nutrients in Cell culture (SILEC) in Pan6 deficient yeast cells. Efficiency and consistency of labeling were also increased, likely due to the stringently defined and reproducible conditions used for yeast culture. The yeast SILEC method greatly enhances the ease of use and accessibility of labeled CoA thioesters and also provides proof-of-concept for generating other labeled metabolites in yeast mutants. PMID:25572876

Differential Substrate Specificity and Kinetic Behavior of Escherichia coli YfdW and Oxalobacter formigenes Formyl Coenzyme A Transferase▿ †

PubMed Central

Toyota, Cory G.; Berthold, Catrine L.; Gruez, Arnaud; Jónsson, Stefán; Lindqvist, Ylva; Cambillau, Christian; Richards, Nigel G. J.

2008-01-01

The yfdXWUVE operon appears to encode proteins that enhance the ability of Escherichia coli MG1655 to survive under acidic conditions. Although the molecular mechanisms underlying this phenotypic behavior remain to be elucidated, findings from structural genomic studies have shown that the structure of YfdW, the protein encoded by the yfdW gene, is homologous to that of the enzyme that mediates oxalate catabolism in the obligate anaerobe Oxalobacter formigenes, O. formigenes formyl coenzyme A transferase (FRC). We now report the first detailed examination of the steady-state kinetic behavior and substrate specificity of recombinant, wild-type YfdW. Our studies confirm that YfdW is a formyl coenzyme A (formyl-CoA) transferase, and YfdW appears to be more stringent than the corresponding enzyme (FRC) in Oxalobacter in employing formyl-CoA and oxalate as substrates. We also report the effects of replacing Trp-48 in the FRC active site with the glutamine residue that occupies an equivalent position in the E. coli protein. The results of these experiments show that Trp-48 precludes oxalate binding to a site that mediates substrate inhibition for YfdW. In addition, the replacement of Trp-48 by Gln-48 yields an FRC variant for which oxalate-dependent substrate inhibition is modified to resemble that seen for YfdW. Our findings illustrate the utility of structural homology in assigning enzyme function and raise the question of whether oxalate catabolism takes place in E. coli upon the up-regulation of the yfdXWUVE operon under acidic conditions. PMID:18245280

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

2016-01-01

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

Breed and trait preferences of Sheko cattle keepers in southwestern Ethiopia.

PubMed

Desta, Takele Taye; Ayalew, Workneh; Hegde, B P

2011-04-01

Like their smallholder subsistence counterparts in developing countries, breed and trait preferences of Sheko cattle keepers have broad perspectives. Our study has documented breed and trait preferences of Sheko cattle keepers in southwestern Ethiopia--the natural breeding tract of Sheko cattle. Our results showed that due to their multifunctionality, cattle are the most preferred livestock species. Overall, farmers showed slightly more preference to local Zebus over Sheko breed. This is due to voracious feeding behavior of Sheko cattle, which make them less preferable in the face of worsening feed shortage, and due to aggressive temperament of Sheko cattle. This is despite Sheko's outperforming potential over local Zebus in their milk production, draft power, and hardiness. At trait level, overall milk production was consistently reported as the most preferred trait followed by fertility and traction. This trait preference rank has matched with the reported frequency count ranks for Sheko cattle use. However, breed preference rank has not matched with reported trait preference ranks because Sheko excels local Zebus in all the three most preferred traits, but it was ranked second. Therefore, to minimize these conflicting interests, breed management plans for Sheko cattle should target on strategies that help to solve feed shortage problem and to improve feeding practices, and on selection of less aggressive Sheko cattle. Therefore, these strategies should be considered in line with Sheko cattle conservation and genetic improvement programs.

Prostate cancer survivors with a passive role preference in treatment decision-making are less satisfied with information received: Results from the PROFILES registry.

PubMed

Cuypers, Maarten; Lamers, Romy E D; de Vries, Marieke; Husson, Olga; Kil, Paul J M; van de Poll-Franse, Lonneke V

2016-11-01

To investigate decision-making role preferences and their association with the evaluation of information received in a sample of low-risk and intermediate-risk prostate cancer (Pca) survivors. Cross-sectional study involved 562 men diagnosed with low-risk or intermediate-risk Pca (median time since diagnosis, 48mo), measuring preferred decision-making role (Control Preference Scale) and the evaluation of information received (EORTC QLQ-INFO25). Analyses were performed using analysis of variance, chi-square tests, and multivariable linear regression models. Men who preferred a passive role were older and less educated than other preference groups and more often selected a noninvasive treatment option (all with P<0.001). The passive role preference group reported having received less information, judged the received information as less helpful, and indicated lower overall satisfaction with information received (all with P<0.05). Role preference groups did not differ in their desire to receive more information. Compared with nonpassive preference groups, the preference for a passive role in Pca treatment decision-making is associated with less satisfaction with the information received. Assessment of role preferences and tailored information provision could improve satisfaction with information received and perhaps may ultimately lead to improved patient participation in treatment decision-making. Copyright © 2016 Elsevier Inc. All rights reserved.

Changing Less-Preferred Duties to More-Preferred: A Potential Strategy for Improving Supervisor Work Enjoyment

ERIC Educational Resources Information Center

Green, Carolyn W.; Reid, Dennis H.; Passante, Susan; Canipe, Vicki

2008-01-01

We evaluated a strategy for making highly nonpreferred work duties more preferred as a potential means of enhancing work enjoyment among supervisors in a human service setting. Repeated preference ratings and rankings were completed by 4 supervisors during baseline to identify their most disliked work tasks. These tasks were then altered by…

Learning Preferences and Impacts of Education Programs in Dog Health Programs in Five Rural and Remote Australian Indigenous Communities

ERIC Educational Resources Information Center

Constable, Sophie; Dixon, Roselyn; Dixon, Robert

2011-01-01

As part of strategies to improve dog and community health in rural and remote Indigenous communities, this study investigated preferences and impacts of dog health education programs. Semistructured interviews with 63 residents from five communities explored learning preferences. Though each community differed, on average yarning was preferred by…

Evidence for two immunologically distinct acetyl-coenzyme A synthetases in yeast

NASA Technical Reports Server (NTRS)

Satyanarayana, T.; Mandel, A. D.; Klein, H. P.

1974-01-01

Evidence is presented that clearly establishes the presence of two acetyl-CoA synthetases in Saccharomyces cerevisiae, one elaborated under 'aerobic' conditions, the other under 'nonaerobic' conditions. The antibody produced by each enzyme is immunologically specific.

Stereospecificity of NAD+/NADH Reactions: A Project Experiment for Advanced Undergraduates.

ERIC Educational Resources Information Center

Lowrey, Jonathan S.; And Others

1981-01-01

Presents background information, materials needed, and experimental procedures to study enzymes dependent on pyridine nucleotide coenzymes (NAD/NADH). The experiments, suitable for advanced organic or biochemistry courses, require approximately 10-15 hours to complete. (SK)

Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

PubMed

Kofoed, Melissa A; Wampler, David A; Pandey, Arti S; Peters, John W; Ensign, Scott A

2011-09-01

NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the aforementioned site-directed mutants. We interpreted and rationalized these results in terms of a mechanism of catalysis for 2-KPCC employing a unique hydrophobic active-site architecture promoting thioether bond cleavage and enolacetone formation not seen for other DSOR enzymes. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Consumer preference models: fuzzy theory approach

NASA Astrophysics Data System (ADS)

Turksen, I. B.; Wilson, I. A.

1993-12-01

Consumer preference models are widely used in new product design, marketing management, pricing and market segmentation. The purpose of this article is to develop and test a fuzzy set preference model which can represent linguistic variables in individual-level models implemented in parallel with existing conjoint models. The potential improvements in market share prediction and predictive validity can substantially improve management decisions about what to make (product design), for whom to make it (market segmentation) and how much to make (market share prediction).

Swedish dental hygienists' preferences for workplace improvement and continuing professional development.

PubMed

Petrén, V; Levin, G; Chohan, T; Preber, H; Candell, A; Bergström, J

2005-08-01

The present study examined factors for workplace improvement and continuing professional development (CPD) for Swedish dental hygienists. Seventy-one per cent of 577 randomly selected members of Sweden's Dental Hygienist Association responded to a questionnaire. The chi-square test, Spearman's rank correlation, and multiple stepwise logistic regression modelling were used in the statistical analysis. The results showed that dental hygienists having more than 10 sick days annually and with a strong commitment to their work increased the preference for workplace improvements, such as peer recognition of dental hygienists' professional qualifications, clinical process quality, and time for reading research articles and participating in projects. In addition, dental hygienists in the 41-52 age group were associated with workplace improvements. This is in contrast to the factors that decreased preferences for workplace improvements: clear work roles, a 1-year training programme, a male clinic manager, and working in the private sector. Practicing dental hygiene in the public sector and lifestyle factors were the most influential determinants for a strong interest in CPD. Workplaces should observe people that are obviously committed to their work, those with many sick days, and those in a specific age group, as they indicate different preferences for workplace improvements. CPD seems to be a lower priority than workplace improvements for Swedish dental hygienists.

Tailoring risk communication to improve comprehension: Do patient preferences help or hurt?

PubMed

Barnes, Andrew J; Hanoch, Yaniv; Miron-Shatz, Talya; Ozanne, Elissa M

2016-09-01

Risk communication tools can facilitate patients' understanding of risk information. In this novel study, we examine the hypothesis that risk communication methods tailored to individuals' preferences can increase risk comprehension. Preferences for breast cancer risk formats, and risk comprehension data were collected using an online survey from 361 women at high risk for breast cancer. Women's initial preferences were assessed by asking them which of the following risk formats would be the clearest: (a) percentage, (b) frequency, (c) bar graph, (d) pictogram, and (e) comparison to other women. Next, women were presented with 5 different formats for displaying cancer risks and asked to interpret the risk information presented. Finally, they were asked again which risk format they preferred. Initial preferences for risk formats were not associated with risk comprehension scores. However, women with lower risk comprehension scores were more likely to update their risk format preferences after they evaluated risks in different formats. Less numerate women were more likely to prefer graphical rather than numeric risk formats. Importantly, we found that women preferring graphical risk formats had lower risk comprehension in these formats compared to numeric formats. In contrast, women preferring numeric formats performed equally well across formats. Our findings suggest that tailoring risk communication to patient preferences may not improve understanding of medical risks, particularly for less numerate women, and point to the potential perils of tailoring risk communication formats to patient preferences. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Defined tetra-allelic gene disruption of the 4-coumarate:coenzyme A ligase 1 (Pv4CL1) gene by CRISPR/Cas9 in switchgrass results in lignin reduction and improved sugar release.

PubMed

Park, Jong-Jin; Yoo, Chang Geun; Flanagan, Amy; Pu, Yunqiao; Debnath, Smriti; Ge, Yaxin; Ragauskas, Arthur J; Wang, Zeng-Yu

2017-01-01

The development of genome editing technologies offers new prospects in improving bioenergy crops like switchgrass ( Panicum virgatum ). Switchgrass is an outcrossing species with an allotetraploid genome (2 n  = 4 x  = 36), a complexity which forms an impediment to generating homozygous knock-out plants. Lignin, a major component of the plant cell wall and a contributor to cellulosic feedstock's recalcitrance to decomposition, stands as a barrier to efficient biofuel production by limiting enzyme access to cell wall polymers during the fermentation process. We developed a CRISPR/Cas9 genome editing system in switchgrass to target a key enzyme involved in the early steps of monolignol biosynthesis, 4-Coumarate:coenzyme A ligase (4CL). Three 4CL genes, Pv4CL1 , Pv4CL2, and Pv4CL3 , were identified in switchgrass. Expression analysis revealed that Pv4CL1 transcripts were more abundant in the stem than in the leaf, while Pv4CL2 transcripts were barely detectable and Pv4CL3 was mainly expressed in the leaf. Pv4CL1 was selected as the target for CRISPR/Cas9 editing because of its preferential expression in highly lignified stem tissues. Specific guide RNA was constructed to target Pv4CL1 . After introducing the construct into switchgrass calli, 39 transgenic plants were regenerated. Using two rounds of PCR screening and sequencing, four plants were confirmed to have tetra-allelic mutations simultaneously. The Pv4CL1 knock-out plants had reduced cell wall thickness, an 8-30% reduction in total lignin content, a 7-11% increase in glucose release, and a 23-32% increase in xylose release. This study established a successful CRISPR/Cas9 system in switchgrass with mutation efficiency reaching 10%. The system allows the precise targeting of the selected Pv4CL1 gene to create switchgrass knock-out mutant plants with decreased lignin content and reduced recalcitrance.

Effects of dietary L-carnitine and coenzyme Q10 at different supplemental ages on growth performance and some immune response in ascites-susceptible broilers.

PubMed

Geng, Ailian; Li, Baoming; Guo, Yuming

2007-02-01

Effects of dietary L-carnitine and coenzyme Q10 (CoQ10) at different supplemental ages on performance and some immune response were investigated in ascites-susceptible broilers. A 3 x 2 x 2 factorial design was used consisting of L-carnitine supplementation (0, 75, and 100 mg/kg), CoQ10 supplementation (0 and 40 mg/kg) and different supplemental ages (from day 1 on and from day 10 on). A total of 480 one-day-old Arbor Acre male broiler chicks were randomly allocated to 12 groups, every group had five replicates, each with eight birds. The birds were fed a corn-soybean based diet for six weeks. From day 10-21, all the birds were exposed to a low ambient temperature (12-15 degrees C) to increase the susceptibility to ascites. No significant effects were observed on growth performance by L-carnitine, CoQ10 supplementation, and different supplemental ages. Packed cell volume was significantly decreased by L-carnitine supplementation alone, and ascites heart index and ascites mortality were decreased by L-carnitine, CoQ10 supplementation alone, and L-carnitine + CoQ10 supplementation together (p < 0.05). Heart index of broilers was significantly improved by L-carnitine, CoQ10 supplementation alone during 0-3 week. Serum IgG content was improved by L-carnitine supplementation alone (p < 0.05), but lysozyme activity was increased by L-carnitine + CoQ10 supplementation together (p < 0.05). A significant L-carnitine by supplemental age interaction was observed in lysozyme activity. L-carnitine supplementation alone had no effects on the peripheral blood lymphocyte (PBL) proliferation in response to concanavalin A (ConA) and lipopolysaccharide, but supplemental CoQ10 alone and L-carnitine+ CoQ10 together decreased the PBL proliferation in response to ConA (p < 0.05). The present study suggested that L-carnitine + CoQ10 supplementation together had positive effects on some immune response of ascites-susceptible broilers, which might benefit for the reduction of broilers' susceptibility to ascites.

Public Preferences Regarding Informed Consent Models for Participation in Population-based Genomic Research

PubMed Central

Platt, Jodyn; Bollinger, Juli; Dvoskin, Rachel; Kardia, Sharon LR; Kaufman, David

2013-01-01

Purpose Some large population biobanks that house biospecimens and health information for research seek broad consent from participants, while others re-consent for specific new studies. Understanding research participants’ attitudes and preferences about broad and narrow consent may improve recruitment, retention, and public support. Methods An online survey was conducted among a representative sample of 4,659 US adults to examine relationships between consent preferences and demographic factors, beliefs about privacy, the value of research, and the perceived trustworthiness of researchers. Results Participants preferred broad consent (52%) over study-by-study consent models (48%). Higher preferences for study-by-study consent observed among Black non-Hispanic respondents, and respondents with lower income and education were explained by differences in the prevalence of one or more beliefs about the study. Respondents with fears about research and those that would feel respected if asked for permission for each research use preferred study-by-study consent. Preference for broad consent was related to the desire not to be bothered with multiple requests and the belief that the study could lead to improved treatments, cures, and lives saved. Conclusion These data suggest that support for broad consent is contingent on sufficient information about data use. Work with research participants and community leaders to understand, respond to, and influence opinions about a given, ongoing study may improve uptake of broad consent. PMID:23660530

A Land-Plant-Specific Glycerol-3-Phosphate Acyltransferase Family in Arabidopsis: Substrate Specificity, sn-2 Preference, and Evolution1[W][OA

PubMed Central

Yang, Weili; Simpson, Jeffrey P.; Li-Beisson, Yonghua; Beisson, Fred; Pollard, Mike; Ohlrogge, John B.

2012-01-01

Arabidopsis (Arabidopsis thaliana) has eight glycerol-3-phosphate acyltransferase (GPAT) genes that are members of a plant-specific family with three distinct clades. Several of these GPATs are required for the synthesis of cutin or suberin. Unlike GPATs with sn-1 regiospecificity involved in membrane or storage lipid synthesis, GPAT4 and -6 are unique bifunctional enzymes with both sn-2 acyltransferase and phosphatase activity resulting in 2-monoacylglycerol products. We present enzymology, pathway organization, and evolutionary analysis of this GPAT family. Within the cutin-associated clade, GPAT8 is demonstrated as a bifunctional sn-2 acyltransferase/phosphatase. GPAT4, -6, and -8 strongly prefer C16:0 and C18:1 ω-oxidized acyl-coenzyme As (CoAs) over unmodified or longer acyl chain substrates. In contrast, suberin-associated GPAT5 can accommodate a broad chain length range of ω-oxidized and unsubstituted acyl-CoAs. These substrate specificities (1) strongly support polyester biosynthetic pathways in which acyl transfer to glycerol occurs after oxidation of the acyl group, (2) implicate GPAT specificities as one major determinant of cutin and suberin composition, and (3) argue against a role of sn-2-GPATs (Enzyme Commission 2.3.1.198) in membrane/storage lipid synthesis. Evidence is presented that GPAT7 is induced by wounding, produces suberin-like monomers when overexpressed, and likely functions in suberin biosynthesis. Within the third clade, we demonstrate that GPAT1 possesses sn-2 acyltransferase but not phosphatase activity and can utilize dicarboxylic acyl-CoA substrates. Thus, sn-2 acyltransferase activity extends to all subbranches of the Arabidopsis GPAT family. Phylogenetic analyses of this family indicate that GPAT4/6/8 arose early in land-plant evolution (bryophytes), whereas the phosphatase-minus GPAT1 to -3 and GPAT5/7 clades diverged later with the appearance of tracheophytes. PMID:22864585

Preferences for physician services in Ukraine: a discrete choice experiment.

PubMed

Danyliv, Andriy; Pavlova, Milena; Gryga, Irena; Groot, Wim

2015-01-01

Evidence on preferences of Ukrainian consumers for healthcare improvements can help to design reforms that correspond to societal priorities. This study aims to elicit and to place monetary values on public preferences for out-patient physician services in Ukraine. The method of discrete choice experiment is used on a sample of 303 respondents, representative of the adult Ukrainian population. The random effect logit model with interactions provides the best fit for the data and is used to calculate the marginal willingness to pay (MWTP) for quality and access improvements. At a sample level, there is no clear preference to pay formally rather than informally or vice versa. We also do not find that visiting a general practitioner is preferred over direct access to a medical specialist. However, there are differences between population groups. Quality-related attributes of physician services appear important to respondents, especially the attitude of medical staff. Thus, interpersonal aspects of out-patient care should be given priority in decisions about investments in quality improvements. Other aspects, that is social quality and access, are important as well but their improvement brings fewer social gains. Measures should be taken to eradicate the informal payment channels and to strengthen the gate-keeping role of primary care. Copyright © 2014 John Wiley & Sons, Ltd.

Characterizing and improving the sensory and hedonic responses to polyphenol-rich aronia berry juice.

PubMed

Duffy, Valerie B; Rawal, Shristi; Park, Jeeha; Brand, Mark H; Sharafi, Mastaneh; Bolling, Bradley W

2016-12-01

Interest in nutrient-rich berry juices is growing, but their high polyphenol levels render them sensorily unappealing. Fifty adults, who were assessed for sensory phenotype and dietary behaviors, provided sensory and palatability ratings of juices from 'Viking' aronia berries for each of seven harvest weeks. By peak harvest, juice preference increased two-fold, averaging neither like/dislike. This hedonic shift was associated with: increases in juice sugars paralleling increases in perceived sweetness (maximum = weak); reductions in percent acidity paralleling reductions in sourness (minimum = moderate), astringency (minimum = to just above weak) and bitterness (minimum = just below weak). About 25% of adults liked the aronia juice, including adults who also liked an aqueous citric acid solution (average rating = moderately sour) or those who reported adventurous eating behaviors. Bitter taste phenotype, measured by propylthiouracil or quinine bitterness, failed to explain significant variation in juice sensation or preference. We also collected sensory and preference ratings from juice collected at peak harvest blended with sugar and/or sweet olfactory flavoring (10 ppm ethyl butyrate). Increasing juice sweetness by adding 5% sucrose decreased sourness and improved preference from weak dislike to weak like. Adding sweet olfactory flavoring decreased juice sourness without changing preference. Adding sweet flavoring and 3% sucrose resulted in reduction of sourness and improvements in preference ratings comparable to 5% added sucrose. Neither added sugar nor flavoring blocked juice astringency. In summary, these findings suggest that aronia juice, even from berries picked at peak harvest, appealed to only a few adults (sour likers or adventurous eaters). Although enhanced sweetness, with added sugar and sweet olfactory flavoring, improved aronia juice preference, broader sensory approaches are required to blunt astringency for greater consumer appeal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterizing and improving the sensory and hedonic responses to polyphenol-rich aronia berry juice

PubMed Central

Duffy, Valerie B.; Rawal, Shristi; Park, Jeeha; Brand, Mark H.; Sharafi, Mastaneh; Bolling, Bradley W.

2017-01-01

Interest in nutrient-rich berry juices is growing, but their high polyphenol levels render them sensorily unappealing. Fifty adults, who were assessed for sensory phenotype and dietary behaviors, provided sensory and palatability ratings of juices from ‘Viking’ aronia berries for each of seven harvest weeks. By peak harvest, juice preference increased two-fold, averaging neither like/dislike. This hedonic shift was associated with: increases in juice sugars paralleling increases in perceived sweetness (maximum = weak); reductions in percent acidity paralleling reductions in sourness (minimum = moderate), astringency (minimum = to just above weak) and bitterness (minimum = just below weak). About 25% of adults liked the aronia juice, including adults who also liked an aqueous citric acid solution (average rating = moderately sour) or those who reported adventurous eating behaviors. Bitter taste phenotype, measured by propylthiouracil or quinine bitterness, failed to explain significant variation in juice sensation or preference. We also collected sensory and preference ratings from juice collected at peak harvest blended with sugar and/or sweet olfactory flavoring (10 ppm ethyl butyrate). Increasing juice sweetness by adding 5% sucrose decreased sourness and improved preference from weak dislike to weak like. Adding sweet olfactory flavoring decreased juice sourness without changing preference. Adding sweet flavoring and 3% sucrose resulted in reduction of sourness and improvements in preference ratings comparable to 5% added sucrose. Neither added sugar nor flavoring blocked juice astringency. In summary, these findings suggest that aronia juice, even from berries picked at peak harvest, appealed to only a few adults (sour likers or adventurous eaters). Although enhanced sweetness, with added sugar and sweet olfactory flavoring, improved aronia juice preference, broader sensory approaches are required to blunt astringency for greater consumer appeal. PMID:27457970

First Principle and Experimental Study for Site Preferences of Formability Improved Alloying Elements in Mg Crystal

NASA Astrophysics Data System (ADS)

Zeng, Ying; Jiang, Bin; Shi, Ouling; Quan, Gaofen; Al-Ezzi, Salih; Pan, FuSheng

2018-07-01

Some alloying elements (Al, Er, Gd, Li, Mn, Sn, Y, Zn) were proved recently by calculations or experiments to improve the formability of Mg alloys, but ignoring their site preference in Mg crystals during the calculated process. A crystallographic model was built via first principle calculations to predict the site preferences of these elements. Regularities between doping elements and site preferences were summarized. Meanwhile, in the basis of the crystallographic model, a series of formulas were deduced combining the diffraction law. It predicted that a crystal plane with abnormal XRD peak intensity of the Mg-based solid solutions, compared to that of the pure Mg, prefers to possess solute atoms. Thus, three single-phase solid solution alloys were then prepared through an original In-situ Solution Treatment, and their XRD patterns were compared. Finally, the experiment further described the site preferences of these solute atoms in Mg crystal, verifying the calculation results.

First Principle and Experimental Study for Site Preferences of Formability Improved Alloying Elements in Mg Crystal

NASA Astrophysics Data System (ADS)

Zeng, Ying; Jiang, Bin; Shi, Ouling; Quan, Gaofen; Al-Ezzi, Salih; Pan, FuSheng

2018-03-01

Some alloying elements (Al, Er, Gd, Li, Mn, Sn, Y, Zn) were proved recently by calculations or experiments to improve the formability of Mg alloys, but ignoring their site preference in Mg crystals during the calculated process. A crystallographic model was built via first principle calculations to predict the site preferences of these elements. Regularities between doping elements and site preferences were summarized. Meanwhile, in the basis of the crystallographic model, a series of formulas were deduced combining the diffraction law. It predicted that a crystal plane with abnormal XRD peak intensity of the Mg-based solid solutions, compared to that of the pure Mg, prefers to possess solute atoms. Thus, three single-phase solid solution alloys were then prepared through an original In-situ Solution Treatment, and their XRD patterns were compared. Finally, the experiment further described the site preferences of these solute atoms in Mg crystal, verifying the calculation results.

Benefit transfer and spatial heterogeneity of preferences for water quality improvements.

PubMed

Martin-Ortega, J; Brouwer, R; Ojea, E; Berbel, J

2012-09-15

The improvement in the water quality resulting from the implementation of the EU Water Framework Directive is expected to generate substantial non-market benefits. A wide spread estimation of these benefits across Europe will require the application of benefit transfer. We use a spatially explicit valuation design to account for the spatial heterogeneity of preferences to help generate lower transfer errors. A map-based choice experiment is applied in the Guadalquivir River Basin (Spain), accounting simultaneously for the spatial distribution of water quality improvements and beneficiaries. Our results show that accounting for the spatial heterogeneity of preferences generally produces lower transfer errors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Delivering preference for place of death in a specialist palliative care setting.

PubMed

Oxenham, David; Finucane, Anne; Arnold, Elizabeth; Russell, Papiya

2013-01-01

Over the last 10 years, one of the key themes of public policy in palliative care has been achievement of choice in place of death. In Marie Curie Hospice Edinburgh a baseline audit conducted in 2006 showed that only a small proportion (18%) of patients referred to hospice services died at home. The audit also revealed that only 31% of those who expressed a preference to die at home were able to do so, whereas 91% of those who chose a setting other than home achieved their preference. Overall achievement of preferred place of death was 56%. However a significant number of patients (29%) did not have a recorded preference. A programme of quality improvement has continued over the last 7 years to improve identification, communication and achievement of preferred place of death for all patients. The mechanisms to change practice have been: changes to documentation; changes to clinical systems to support use of documentation; support for clinical staff to recognise the value of discussing preferences; and support for clinical staff to develop new skills. In addition the programme has been incorporated into local clinical strategy and this has enabled gaps in service to be addressed with a new service to support early discharge of those patients who wish to die at home. A recent audit showed that all patients had a recorded preference or a documented reason why their preference was unclarified. One third of patients died at home - nearly double the proportion that died at home in the baseline audit. Seventy one per cent of patients who wished to die at home actually died at home - a substantial increase from 31% at baseline. Achievement of preferred place of death for patients wishing to die in the hospice remained high at 88%. The focus on assessment of preference for place of death has led to substantial improvements in the identification and achievement of preference for patients dying under the care of the hospice. Furthermore, it has been associated with an increase in the overall proportion of patients who die at home.

Preferred Learning Styles of Professional Undergraduate and Graduate Athletic Training Students

ERIC Educational Resources Information Center

Thon, Sarah; Hansen, Pamela

2015-01-01

Context: Recognizing the preferred learning style of professional undergraduate and graduate athletic training students will equip educators to more effectively improve their teaching methods and optimize student learning. Objective: To determine the preferred learning style of professional undergraduate and graduate athletic training students…

77 FR 60722 - Certain Coenzyme Q10 Products and Methods of Making Same; Notice of Request for Statements on the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... respondents Zhejiang Medicine Co., Ltd., ZMC-USA, L.L.C., Xiamen Kingdomway Group Company, Pacific Rainbow... and Technology Co., Ltd. FOR FURTHER INFORMATION CONTACT: Lisa R. Barton, Acting Secretary to the...

Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

PubMed

Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

2015-02-01

Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword?

PubMed Central

Balakumar, Pitchai; Mahadevan, Nanjaian

2012-01-01

Statins are best-selling medications in the management of high cholesterol and associated cardiovascular complications. They inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase in order to prevent disproportionate cholesterol synthesis. Statins slow the progression of atherosclerosis, prevent the secondary cardiovascular events and improve the cardiovascular outcomes in patients with elevated cholesterol levels. The underlying mechanisms pertaining to the cardioprotective role of statins are linked with numerous pleiotropic actions including inhibition of inflammatory events and improvement of endothelial function, besides an effective cholesterol-lowering ability. Intriguingly, recent studies suggest possible interplay between statins and nuclear transcription factors like PPARs, which should also be taken into consideration while analysing the potential of statins in the management of cardiovascular complications. It could be suggested that statins have two major roles: (i) a well-established cholesterol-lowering effect through inhibition of HMG-CoA-reductase; (ii) a newly explored PPAR-activating property, which could mediate most of cardiovascular protective pleiotropic effects of statins including anti-inflammatory, antioxidant and anti-fibrotic properties. The present review addressed the underlying principles pertaining to the modulatory role of statins on PPARs. PMID:21790534

High-Yield Resveratrol Production in Engineered Escherichia coli ▿ †

PubMed Central

Lim, Chin Giaw; Fowler, Zachary L.; Hueller, Thomas; Schaffer, Steffen; Koffas, Mattheos A. G.

2011-01-01

Plant polyphenols have been the subject of several recent scientific investigations since many of the molecules in this class have been found to be highly active in the human body, with a plethora of health-promoting activities against a variety of diseases, including heart disease, diabetes, and cancer, and with even the potential to slow aging. Further development of these potent natural therapeutics hinges on the formation of robust industrial production platforms designed using specifically selected as well as engineered protein sources along with the construction of optimal expression platforms. In this work, we first report the investigation of various stilbene synthases from an array of plant species considering structure-activity relationships, their expression efficiency in microorganisms, and their ability to synthesize resveratrol. Second, we looked into the construct environment of recombinantly expressed stilbene synthases, including different promoters, construct designs, and host strains, to create an Escherichia coli strain capable of producing superior resveratrol titers sufficient for commercial usage. Further improvement of metabolic capabilities of the recombinant strain aimed at improving the intracellular malonyl-coenzyme A pool, a resveratrol precursor, resulted in a final improved titer of 2.3 g/liter resveratrol. PMID:21441338

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

PubMed

Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

2017-07-26

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

The ALDH21 gene found in lower plants and some vascular plants codes for a NADP+ -dependent succinic semialdehyde dehydrogenase.

PubMed

Kopečná, Martina; Vigouroux, Armelle; Vilím, Jan; Končitíková, Radka; Briozzo, Pierre; Hájková, Eva; Jašková, Lenka; von Schwartzenberg, Klaus; Šebela, Marek; Moréra, Solange; Kopečný, David

2017-10-01

Lower plant species including some green algae, non-vascular plants (bryophytes) as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated during dehydration. However, the gene is absent in flowering plants. Here, we show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP + -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic semialdehyde, an intermediate of the γ-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol. NAD + is a very poor coenzyme for ALDH21 unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH members. Structural comparison between the apoform and the coenzyme complex reveal that NADP + binding induces a conformational change of the loop carrying Arg-228, which seals the NADP + in the coenzyme cavity via its 2'-phosphate and α-phosphate groups. The crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg-121 and Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre-formed for substrate/product binding, Tyr-296 moves by more than 1 Å. Both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis. Our study implies that bryophytes but presumably also some green algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize SSAL to succinate in both cytosol and mitochondria, indicating a more diverse GABA shunt pathway compared with higher plants carrying only the mitochondrial ALDH5. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Methyl-coenzyme M reductase A as an indicator to estimate methane production from dairy cows.

PubMed

Aguinaga Casañas, M A; Rangkasenee, N; Krattenmacher, N; Thaller, G; Metges, C C; Kuhla, B

2015-06-01

The evaluation of greenhouse gas mitigation strategies requires the quantitative assessment of individual methane production. Because methane measurement in respiration chambers is highly accurate, but also comprises various disadvantages such as limited capacity and high costs, the establishment of an indicator for estimating methane production of individual ruminants would provide an alternative to direct methane measurement. Methyl-coenzyme M reductase is involved in methanogenesis and the subunit α of methyl-coenzyme M reductase is encoded by the mcrA gene of rumen archaea. We therefore examined the relationship between methane emissions of Holstein dairy cows measured in respiration chambers with 2 different diets (high- and medium-concentrate diet) and the mcrA DNA and mcrA cDNA abundance determined from corresponding rumen fluid samples. Whole-body methane production per kilogram of dry matter intake and mcrA DNA normalized to the abundance of the rrs gene coding for 16S rRNA correlated significantly when using qmcrA primers. Use of qmcrA primers also revealed linear correlation between mcrA DNA copy number and methane yield. Regression analyses based on normalized mcrA cDNA abundances revealed no significant linear correlation with methane production per kilogram of dry matter intake. Furthermore, the correlations between normalized mcrA DNA abundance and the rumen fluid concentration of acetic and isobutyric acid were positive, whereas the correlations with propionic and lactic acid were negative. These data suggest that the mcrA DNA approach based on qmcrA primers could potentially be a molecular proxy for methane yield after further refinement. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A paradigm shift for radical SAM reactions: The organometallic intermediate Ω is central to catalysis.

PubMed

Byer, Amanda S; Yang, Hao; McDaniel, Elizabeth C; Kathiresan, Venkatesan; Impano, Stella; Pagnier, Adrien; Watts, Hope; Denler, Carly; Vagstad, Anna; Piel, Jörn; Duschene, Kaitlin S; Shepard, Eric M; Shields, Thomas P; Scott, Lincoln G; Lilla, Edward A; Yokoyama, Kenichi; Broderick, William E; Hoffman, Brian M; Broderick, Joan B

2018-06-28

Radical S-adenosyl-L-methionine (SAM) en-zymes comprise a vast superfamily catalyzing diverse reactions essential to all life through ho-molytic SAM cleavage to liberate the highly-reactive 5-deoxyadenosyl radical (5-dAdo•). Our recent observation of a catalytically compe-tent organometallic intermediate Ω that forms dur-ing reaction of the radical SAM (RS) enzyme py-ruvate formate-lyase activating-enzyme (PFL-AE) was therefore quite surprising, and led to the question of its broad relevance in the superfamily. We now show that Ω in PFL-AE forms as an in-termediate under a variety of mixing order condi-tions, suggesting it is central to catalysis in this enzyme. We further demonstrate that Ω forms in a suite of RS enzymes chosen to span the totality of superfamily reaction types, implicating Ω as essential in catalysis across the RS superfamily. Finally, EPR and electron nuclear double reso-nance spectroscopy establish that Ω involves an Fe-C5 bond between 5-dAdo• and the [4Fe-4S] cluster. An analogous organometallic bond is found in the well-known adenosylcobalamin (co-enzyme B12) cofactor used to initiate radical reac-tions via a 5'-dAdo• intermediate. Generation of a 5'-dAdo• intermediate via homolytic metal-carbon bond cleavage thus appears to be similar for Ω and coenzyme B12. However coenzyme B12 is involved in enzymes catalyzing of only a small number (~12) of distinct reactions, while the RS superfamily has more than 100,000 distinct se-quences and over 80 reaction types character-ized to date. The appearance of Ω across the RS superfamily therefore dramatically enlarges the sphere of bio-organometallic chemistry in Nature.

Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages.

PubMed

Weidner, Thomas; Lucantoni, Leonardo; Nasereddin, Abed; Preu, Lutz; Jones, Peter G; Dzikowski, Ron; Avery, Vicky M; Kunick, Conrad

2017-05-15

Malaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs. Phenotypic screening of a small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54-luc asexual erythrocytic stage parasites identified a diarylthioether structurally unrelated to registered drugs. Hit expansion led to a series in which the most potent congener displayed nanomolar antiparasitic activity (IC 50  = 39 nM, 3D7 strain). Structure-activity relationship analysis revealed a thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite for antiplasmodial activity. Within the series, the oxazole derivative KuWei173 showed high potency (IC 50  = 75 nM; 3D7 strain), good solubility in aqueous solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue experiments identified inhibition of the plasmodial coenzyme A synthesis as a possible mode of action for this compound class. The class of antiplasmodial bishetarylthioethers reported here has been shown to interfere with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for registered anti-malarial drugs. The oxazole congener KuWei173 displays double-digit nanomolar antiplasmodial activity, selectivity against human cell lines, high drug likeness, and thus represents a promising chemical starting point for further drug development.

A comparison of fat-soluble antioxidants in wild and farm-reared chukar partridges (Alectoris chukar).

PubMed

Karadas, Filiz; Møller, Anders Pape; Karageçili, Mehmet Reşit

2017-06-01

This study assessed differences in antioxidant (carotenoid, retinol, retinol-ester, vitamin E and coenzyme Q 10 ) composition of egg yolk and tissue in chukar partridges (Alectoris chukar) newly hatched from eggs of birds maintained in captivity on commercial maize-soybean based diets and birds from the wild whose diet was obtained from the natural environment. All eggs were incubated in a commercial hatchery. Day-old chicks from both groups were sacrificed and dissected for antioxidant analysis. Fat soluble antioxidant concentrations of egg yolk and tissues were determined by HPLC. Total carotenoids, retinol, alpha-tocopherol, and total vitamin E concentration of wild egg yolks were significantly higher compared to yolks from farm-reared birds (p<0.05). However, gamma tocopherol, and coenzyme Q 10 were not significantly different in the yolks of either wild or farmed birds (p>0.05). The concentration of total carotenoids in all tissues of wild chukar one-day old partridges was significantly higher than in farmed one-day old chukar partridge tissues (p<0.05). Alpha tocopherol, free-retinol, retinol-esters and total vitamin A were significantly higher in most tissues of wild chukar when compared to farmed chicks (p<0.05). Coenzyme Q 10 concentrations of heart, kidney and brain tissues of farm-reared chukar day old chicks were significantly higher than tissues from wild birds, although leg and breast tissues of wild chicks were significantly higher than in farmed birds (p<0.05). These findings suggest that maternal access to antioxidants in the diet of farmed chukar partridges could positively influence fat soluble antioxidant concentrations in the egg yolk and tissues of day old chicks. Copyright © 2017 Elsevier Inc. All rights reserved.

A new oral otoprotective agent. Part 1: Electrophysiology data from protection against noise-induced hearing loss

PubMed Central

Cascella, Vincenza; Giordano, Pietro; Hatzopoulos, Stavros; Petruccelli, Joseph; Prosser, Silvano; Simoni, Edi; Astolfi, Laura; Fetoni, Annarita Rita; Skarżyński, Henryk; Martini, Alessandro

2012-01-01

Summary Background Data from animal studies show that antioxidants can compensate against noise-induced stress and sensory hair cell death. The aim of this study was to evaluate the otoprotection efficacy of various versions of orally administered Acuval 400® against noise damage in a rat animal model. Material/Methods Fifty-five Sprague Dawley rats were divided into 4 groups: A) noise-exposed animals; B) animals exposed to noise and treated with the Acuval; C) animals exposed to noise and treated with a combination of Coenzyme Q10 and Acuval; D) animals treated only with Acuval and Coenzyme Q10 and with no exposure to noise. All solutions were administered orally 5 times: 24 and 2 hrs prior to noise exposure, and then daily for 3 days. The auditory function was assessed by measuring auditory brainstem responses (ABR) in the range from 2 to 32 kHz at times =1, 7, 14 and 21 days after noise exposure. Results At low frequencies (click and 4 kHz) animals from both A and B groups showed significant threshold shifts in the majority of the tested frequencies and tested times. For the same frequencies, animals from group C presented threshold levels similar to those from group D. At frequencies ≥8 kHz the protective performance of the 2 Acuval groups is more clearly distinguished from the noise group A. At 32 kHz the 2 Acuval groups perform equally well in terms of otoprotection. Animals in Group D did not show any significant differences in the hearing threshold during the experiment. Conclusions The data of this study suggest that a solution containing Coenzyme Q10 and Acuval 400®, administered orally, protects from noise-induced hearing loss. PMID:22207104

A new oral otoprotective agent. Part 1: Electrophysiology data from protection against noise-induced hearing loss.

PubMed

Cascella, Vincenza; Giordano, Pietro; Hatzopoulos, Stavros; Petruccelli, Joseph; Prosser, Silvano; Simoni, Edi; Astolfi, Laura; Fetoni, Anna Rita; Skarżyński, Henryk; Martini, Alessandro

2012-01-01

Data from animal studies show that antioxidants can compensate against noise-induced stress and sensory hair cell death. The aim of this study was to evaluate the otoprotection efficacy of various versions of orally administered Acuval 400 against noise damage in a rat animal model. Fifty-five Sprague Dawley rats were divided into 4 groups: A) noise-exposed animals; B) animals exposed to noise and treated with the Acuval; C) animals exposed to noise and treated with a combination of Coenzyme Q10 and Acuval; D) animals treated only with Acuval and Coenzyme Q10 and with no exposure to noise. All solutions were administered orally 5 times: 24 and 2 hrs prior to noise exposure, and then daily for 3 days. The auditory function was assessed by measuring auditory brainstem responses (ABR) in the range from 2 to 32 kHz at times =1, 7, 14 and 21 days after noise exposure. At low frequencies (click and 4 kHz) animals from both A and B groups showed significant threshold shifts in the majority of the tested frequencies and tested times. For the same frequencies, animals from group C presented threshold levels similar to those from group D. At frequencies ≥ 8 kHz the protective performance of the 2 Acuval groups is more clearly distinguished from the noise group A. At 32 kHz the 2 Acuval groups perform equally well in terms of otoprotection. Animals in Group D did not show any significant differences in the hearing threshold during the experiment. The data of this study suggest that a solution containing Coenzyme Q10 and Acuval 400, administered orally, protects from noise-induced hearing loss.

TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

NASA Astrophysics Data System (ADS)

Kozlowski, Pawel; Liu, Hui; Kornobis, Karina; Lodowski, Piotr; Jaworska, Maria

2013-12-01

Coenzyme B12 (AdoCbl) is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT) has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl) was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM). Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C) triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl). Furthermore, potential energy surfaces (PESs) obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer) and a σ bonding-ligand charge transfer (SBLCT) states.

NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying G1 arrest and apoptosis.

PubMed

De Luca, Thomas; Morré, Dorothy M; Zhao, Haiyun; Morré, D James

2005-01-01

To elucidate possible biochemical links between growth arrest from antiproliferative chemotherapeutic agents and apoptosis, our work has focused on agents (EGCg, capsaicin, cis platinum, adriamycin, anti-tumor sulfonylureas, phenoxodiol) that target tNOX. tNOX is a cancer-specific cell surface NADH oxidase (ECTO-NOX protein), that functions in cancer cells as the terminal oxidase for plasma membrane electron transport. When tNOX is active, coenzyme Q(10) (ubiquinone) of the plasma membrane is oxidized and NADH is oxidized at the cytosolic surface of the plasma membrane. However, when tNOX is inhibited and plasma membrane electron transport is diminished, both reduced coenzyme Q(10) (ubiquinol) and NADH would be expected to accumulate. To relate inhibition of plasma membrane redox to increased ceramide levels and arrest of cell proliferation in G(1) and apoptosis, we show that neutral sphingomyelinase, a major contributor to plasma membrane ceramide, is inhibited by reduced glutathione and ubiquinone. Ubiquinol is without effect or stimulates. In contrast, sphingosine kinase, which generates anti-apoptotic sphingosine-1-phosphate, is stimulated by ubiquinone but inhibited by ubiquinol and NADH. Thus, the quinone and pyridine nucleotide products of plasma membrane redox, ubiquinone and ubiquinol, as well as NAD(+) and NADH, may directly modulate in a reciprocal manner two key plasma membrane enzymes, sphingomyelinase and sphingosine kinase, potentially leading to G(1) arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). As such, the findings provide potential links between coenzyme Q(10)-mediated plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents.

Coenzyme Q10 and statins: biochemical and clinical implications.

PubMed

Littarru, Gian Paolo; Langsjoen, Peter

2007-06-01

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Fatty Acid Synthesis in Pea Root Plastids Is Inhibited by the Action of Long-Chain Acyl- Coenzyme As on Metabolite Transporters1

PubMed Central

Fox, Simon R.; Rawsthorne, Stephen; Hills, Matthew J.

2001-01-01

The uptake in vitro of glucose (Glc)-6-phosphate (Glc-6-P) into plastids from the roots of 10- to 14-d-old pea (Pisum sativum L. cv Puget) plants was inhibited by oleoyl-coenzyme A (CoA) concentrations in the low micromolar range (1–2 μm). The IC50 (the concentration of inhibitor that reduces enzyme activity by 50%) for the inhibition of Glc-6-P uptake was approximately 750 nm; inhibition was reversed by recombinant rapeseed (Brassica napus) acyl-CoA binding protein. In the presence of ATP (3 mm) and CoASH (coenzyme A; 0.3 mm), Glc-6-P uptake was inhibited by 60%, due to long-chain acyl-CoA synthesis, presumably from endogenous sources of fatty acids present in the preparations. Addition of oleoyl-CoA (1 μm) decreased carbon flux from Glc-6-P into the synthesis of starch and through the oxidative pentose phosphate (OPP) pathway by up to 73% and 40%, respectively. The incorporation of carbon from Glc-6-P into fatty acids was not detected under any conditions. Oleoyl-CoA inhibited the incorporation of acetate into fatty acids by 67%, a decrease similar to that when ATP was excluded from incubations. The oleoyl-CoA-dependent inhibition of fatty acid synthesis was attributable to a direct inhibition of the adenine nucleotide translocator by oleoyl-CoA, which indirectly reduced fatty acid synthesis by ATP deprivation. The Glc-6-P-dependent stimulation of acetate incorporation into fatty acids was reversed by the addition of oleoyl-CoA. PMID:11457976

Production of biofuels and biochemicals by in vitro synthetic biosystems: Opportunities and challenges.

PubMed

Zhang, Yi-Heng Percival

2015-11-15

The largest obstacle to the cost-competitive production of low-value and high-impact biofuels and biochemicals (called biocommodities) is high production costs catalyzed by microbes due to their inherent weaknesses, such as low product yield, slow reaction rate, high separation cost, intolerance to toxic products, and so on. This predominant whole-cell platform suffers from a mismatch between the primary goal of living microbes - cell proliferation and the desired biomanufacturing goal - desired products (not cell mass most times). In vitro synthetic biosystems consist of numerous enzymes as building bricks, enzyme complexes as building modules, and/or (biomimetic) coenzymes, which are assembled into synthetic enzymatic pathways for implementing complicated bioreactions. They emerge as an alternative solution for accomplishing a desired biotransformation without concerns of cell proliferation, complicated cellular regulation, and side-product formation. In addition to the most important advantage - high product yield, in vitro synthetic biosystems feature several other biomanufacturing advantages, such as fast reaction rate, easy product separation, open process control, broad reaction condition, tolerance to toxic substrates or products, and so on. In this perspective review, the general design rules of in vitro synthetic pathways are presented with eight supporting examples: hydrogen, n-butanol, isobutanol, electricity, starch, lactate,1,3-propanediol, and poly-3-hydroxylbutyrate. Also, a detailed economic analysis for enzymatic hydrogen production from carbohydrates is presented to illustrate some advantages of this system and the remaining challenges. Great market potentials will motivate worldwide efforts from multiple disciplines (i.e., chemistry, biology and engineering) to address the remaining obstacles pertaining to cost and stability of enzymes and coenzymes, standardized building parts and modules, biomimetic coenzymes, biosystem optimization, and scale-up, soon. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of different ratios of monounsaturated and polyunsaturated fatty acids to saturated fatty acids on regulating body fat deposition in hamsters.

PubMed

Liao, Fang-Hsuean; Liou, Tsan-Hon; Shieh, Ming-Jer; Chien, Yi-Wen

2010-01-01

Effects of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid consumption on regulating body fat accumulation and body weight gain are controversial between animal and human studies. We designed a 2 x 2 factorial study, with two levels of MUFAs (60% and 30%) and two levels of polyunsaturated-to-saturated fatty acid (P/S) ratio (5 and 3) to prepare four kinds of experimental oils consisting of 60% MUFAs with a high or low P/S ratio (HMHR or HMLR, respectively) or 30% MUFAs with a high or low P/S ratio (LMHR or LMLR, respectively). Thirty-two male golden Syrian hamsters were randomly divided into four groups and fed the experimental diets containing 15% (w/w) fat for 12 wk. No difference was observed in the mean daily food intake. Hamsters fed the LMLR diet had increased weight gain, epididymal and retroperitoneal white adipose tissues, plasma non-esterified fatty acids, insulin, hepatic acetyl coenzyme A carboxylase and malic enzyme activities, and mRNA expressions of peroxisome proliferator-activated receptor-alpha and sterol regulatory element-binding protein-1c among all groups (P < 0.05). Hamsters fed the HMHR diet had lower plasma insulin levels and hepatic acetyl coenzyme A carboxylase activities among groups (P < 0.05) and elevated hepatic acyl coenzyme A oxidase and carnitine palmitoyltransferase-I activities compared with those fed the LMLR diet (P < 0.05). Hamsters fed the LMLR diet had increased weight gain and body fat accumulation, whereas the HMHR diet appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in beta-oxidation. 2010 Elsevier Inc. All rights reserved.

Thermodynamic and NMR analyses of NADPH binding to lipocalin-type prostaglandin D synthase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Shubin; Shimamoto, Shigeru; Maruno, Takahiro

2015-12-04

Lipocalin-type prostaglandin D synthase (L-PGDS) is one of the most abundant proteins in human cerebrospinal fluid (CSF) with dual functions as a prostaglandin D{sub 2} (PGD{sub 2}) synthase and a transporter of lipophilic ligands. Recent studies revealed that L-PGDS plays important roles in protecting against various neuronal diseases induced by reactive oxygen species (ROS). However, the molecular mechanisms of such protective actions of L-PGDS remain unknown. In this study, we conducted thermodynamic and nuclear magnetic resonance (NMR) analyses, and demonstrated that L-PGDS binds to nicotinamide coenzymes, including NADPH, NADP{sup +}, and NADH. Although a hydrophilic ligand is not common formore » L-PGDS, these ligands, especially NADPH showed specific interaction with L-PGDS at the upper pocket of its ligand-binding cavity with an unusually bifurcated shape. The binding affinity of L-PGDS for NADPH was comparable to that previously reported for NADPH oxidases and NADPH in vitro. These results suggested that L-PGDS potentially attenuates the activities of NADPH oxidases through interaction with NADPH. Given that NADPH is the substrate for NADPH oxidases that play key roles in neuronal cell death by generating excessive ROS, these results imply a novel linkage between L-PGDS and ROS. - Highlights: • Interactions of L-PGDS with nicotinamide coenzymes were studied by ITC and NMR. • The binding affinity of L-PGDS was strongest to NADPH among nicotinamide coenzymes. • NADPH binds to the upper part of L-PGDS ligand-binding cavity. • L-PGDS binds to both lipophilic and hydrophilic ligands. • This study implies a novel linkage between L-PGDS and reactive oxygen species.« less

Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells

PubMed Central

Fink, Brian D.; O'Malley, Yunxia; Dake, Brian L.; Ross, Nicolette C.; Prisinzano, Thomas E.; Sivitz, William I.

2009-01-01

Background Previously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and Results To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. Conclusions In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level. PMID:19158951

Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in endothelial cells.

PubMed

Fink, Brian D; O'Malley, Yunxia; Dake, Brian L; Ross, Nicolette C; Prisinzano, Thomas E; Sivitz, William I

2009-01-01

Previously, we reported that the "antioxidant" compound "mitoQ" (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level.

Investigation of Phenolic Acids in Suspension Cultures of Vitis vinifera Stimulated with Indanoyl-Isoleucine, N-Linolenoyl-L-Glutamine, Malonyl Coenzyme A and Insect Saliva

PubMed Central

Riedel, Heidi; Akumo, Divine N.; Saw, Nay Min Min Thaw; Smetanska, Iryna; Neubauer, Peter

2012-01-01

Vitis vinifera c.v. Muscat de Frontignan (grape) contains various high valuable bioactive phenolic compounds with pharmaceutical properties and industrial interest which are not fully exploited. The focus of this investigation consists in testing the effects of various biological elicitors on a non-morphogenic callus suspension culture of V. vinifera. The investigated elicitors: Indanoyl-isoleucine (IN), N-linolenoyl-L-glutamine (LG), insect saliva (IS) and malonyl coenzyme A (MCoA) were aimed at mimicking the influence of environmental pathogens on plants in their natural habitats and at provoking exogenous induction of the phenylpropanoid pathway. The elicitors’ indanoyl-isoleucine (IN), N-linolenoyl-L-glutamine (LG) and insect saliva (IS), as well as malonyl coenzyme A (MCoA), were independently inoculated to stimulate the synthesis of phenylpropanoids. All of the enhancers positively increased the concentration of phenolic compounds in grape cells. The highest concentration of phenolic acids was detected after 2 h for MCoA, after 48 h for IN and after 24 h for LG and IS respectively. At the maximum production time, treated grape cells had a 3.5-fold (MCoA), 1.6-fold (IN) and 1.5-fold (IS) higher phenolic acid content compared to the corresponding control samples. The HPLC results of grape cells showed two major resveratrol derivatives: 3-O-Glucosyl-resveratrol and 4-(3,5-dihydroxyphenyl)-phenol. Their influences of the different elicitors, time of harvest and biomass concentration (p < 0.0001) were statistically significant on the synthesis of phenolic compounds. The induction with MCoA was found to demonstrate the highest statistical effect corresponding to the strongest stress response within the phenylpropanoid pathway in grape cells. PMID:24957372

The reaction mechanism of methyl-coenzyme M reductase: How an enzyme enforces strict binding order

DOE PAGES

Wongnate, Thanyaporn; Ragsdale, Stephen W.

2015-02-17

Methyl-coenzyme M reductase (MCR) is a nickel tetrahydrocorphinoid (coenzyme F430) containing enzyme involved in the biological synthesis and anaerobic oxidation of methane. MCR catalyzes the conversion of methyl-2-mercaptoethanesulfonate (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoB 7SH) to CH 4 and the mixed disulfide CoBS-SCoM. In this study, the reaction of MCR from Methanothermobacter marburgensis, with its native substrates was investigated using static binding, chemical quench, and stopped-flow techniques. Rate constants were measured for each step in this strictly ordered ternary complex catalytic mechanism. Surprisingly, in the absence of the other substrate, MCR can bind either substrate; however, only one binary complex (MCR·methyl-SCoM)more » is productive whereas the other (MCR·CoB 7SH) is inhibitory. Moreover, the kinetic data demonstrate that binding of methyl-SCoM to the inhibitory MCR·CoB 7SH complex is highly disfavored ( Kd = 56 mM). However, binding of CoB 7SH to the productive MCR·methyl-SCoM complex to form the active ternary complex (CoB 7SH·MCR(Ni I)·CH 3SCoM) is highly favored ( Kd = 79 μM). Only then can the chemical reaction occur ( kobs = 20 s -1 at 25 °C), leading to rapid formation and dissociation of CH 4 leaving the binary product complex (MCR(Ni II)·CoB 7S -·SCoM), which undergoes electron transfer to regenerate Ni(I) and the final product CoBS-SCoM. In conclusion, this first rapid kinetics study of MCR with its natural substrates describes how an enzyme can enforce a strictly ordered ternary complex mechanism and serves as a template for identification of the reaction intermediates.« less

Tb3+-cleavage assays reveal specific Mg2+ binding sites necessary to pre-fold the btuB riboswitch for AdoCbl binding

NASA Astrophysics Data System (ADS)

Choudhary, Pallavi K.; Gallo, Sofia; Sigel, Roland K. O.

2017-03-01

Riboswitches are RNA elements that bind specific metabolites in order to regulate the gene expression involved in controlling the cellular concentration of the respective molecule or ion. Ligand recognition is mostly facilitated by Mg2+ mediated pre-organization of the riboswitch to an active tertiary fold. To predict these specific Mg2+ induced tertiary interactions of the btuB riboswitch from E. coli, we here report Mg2+ binding pockets in its aptameric part in both, the ligand-free and the ligand-bound form. An ensemble of weak and strong metal ion binding sites distributed over the entire aptamer was detected by terbium(III) cleavage assays, Tb3+ being an established Mg2+ mimic. Interestingly many of the Mn+ (n = 2 or 3) binding sites involve conserved bases within the class of coenzyme B12-binding riboswitches. Comparison with the published crystal structure of the coenzyme B12 riboswitch of S. thermophilum aided in identifying a common set of Mn+ binding sites that might be crucial for tertiary interactions involved in the organization of the aptamer. Our results suggest that Mn+ binding at strategic locations of the btuB riboswitch indeed facilitates the assembly of the binding pocket needed for ligand recognition. Binding of the specific ligand, coenzyme B12 (AdoCbl), to the btuB aptamer does however not lead to drastic alterations of these Mn+ binding cores, indicating the lack of a major rearrangement within the three-dimensional structure of the RNA. This finding is strengthened by Tb3+ mediated footprints of the riboswitch's structure in its ligand-free and ligand-bound state indicating that AdoCbl indeed induces local changes rather than a global structural rearrangement.

Improving the performance of solventogenic clostridia by reinforcing the biotin synthetic pathway.

PubMed

Yang, Yunpeng; Lang, Nannan; Yang, Gaohua; Yang, Sheng; Jiang, Weihong; Gu, Yang

2016-05-01

An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of solventogenic clostridia, we revealed that the insufficient biosynthesis of biotin, a pivotal coenzyme for many important biological processes, is a major limiting bottleneck in this anaerobe's performance. To address this problem, we strengthened the biotin synthesis of C. acetobutylicum by overexpressing four relevant genes involved in biotin transport and biosynthesis. This strategy led to faster growth and improved the titer and productivity of acetone, butanol and ethanol (ABE solvents) of C. acetobutylicum in both biotin-containing and biotin-free media. Expressionally modulating these four genes by modifying the ribosome binding site further promoted cellular performance, achieving ABE solvent titer and productivity as high as 21.9g/L and 0.30g/L/h, respectively, in biotin-free medium; these values exceeded those of the wild-type strain by over 30%. More importantly, biotin synthesis reinforcement also conferred improved ability of C. acetobutylicum to use hexose and pentose sugars, further demonstrating the potential of this metabolic-engineering strategy in solventogenic clostridia. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Characterization of a novel strain phylogenetically related to Kocuria rhizophila and its chemical modification to improve performance of microbial fuel cells.

PubMed

Luo, Jianmei; Li, Ming; Zhou, Minghua; Hu, Youshuang

2015-07-15

It is certainly an important research area to discovery new exoelectrogens for microbial fuel cells (MFCs), and how to effectively manipulate its cell property to improve power performance is still a great challenge. In this study, a new electrochemically active bacterium phylogenetically related to Kocuria rhizophila was first isolated and found electrogenic in MFCs, which was identified through the combination methods of molecular biology, physiological, biochemical and morphological characteristics. The MFCs inoculated with this strain generated power from a wide variety of substrates, reached a maximum power density of 75mW/m(2) in the substrate of 1g/L glucose. And the electron transfer mechanism was confirmed to be dominantly direct biofilm mechanism. Chemical treatment with five reagents was verified to be a feasible strategy to improve the power density of MFCs, increasing approximately 1.75 fold at most after treated with lysozyme. This enhancement was contributed to the significant enhancement on cell permeability, cell membrane fluidity and Coenzyme Q10 (the electron carrier). Thus this work offered a novel Gram-positive electrogenic bacterium and proved chemical treatment was a feasible strategy to improve electron transfer for application in MFCs. Copyright © 2015 Elsevier B.V. All rights reserved.

Purification of a jojoba embryo wax synthase, cloning of its cDNA, and production of high levels of wax in seeds of transgenic arabidopsis.

PubMed

Lardizabal, K D; Metz, J G; Sakamoto, T; Hutton, W C; Pollard, M R; Lassner, M W

2000-03-01

Wax synthase (WS, fatty acyl-coenzyme A [coA]: fatty alcohol acyltransferase) catalyzes the final step in the synthesis of linear esters (waxes) that accumulate in seeds of jojoba (Simmondsia chinensis). We have characterized and partially purified this enzyme from developing jojoba embryos. A protein whose presence correlated with WS activity during chromatographic fractionation was identified and a cDNA encoding that protein was cloned. Seed-specific expression of the cDNA in transgenic Arabidopsis conferred high levels of WS activity on developing embryos from those plants. The WS sequence has significant homology with several Arabidopsis open reading frames of unknown function. Wax production in jojoba requires, in addition to WS, a fatty acyl-CoA reductase (FAR) and an efficient fatty acid elongase system that forms the substrates preferred by the FAR. We have expressed the jojoba WS cDNA in Arabidopsis in combination with cDNAs encoding the jojoba FAR and a beta-ketoacyl-CoA synthase (a component of fatty acid elongase) from Lunaria annua. (13)C-Nuclear magnetic resonance analysis of pooled whole seeds from transgenic plants indicated that as many as 49% of the oil molecules in the seeds were waxes. Gas chromatography analysis of transmethylated oil from individual seeds suggested that wax levels may represent up to 70% (by weight) of the oil present in those seeds.

Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency.

PubMed

Hannibal, Luciana; Lysne, Vegard; Bjørke-Monsen, Anne-Lise; Behringer, Sidney; Grünert, Sarah C; Spiekerkoetter, Ute; Jacobsen, Donald W; Blom, Henk J

2016-01-01

Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status. Clinically, vitamin B12 deficiency leads to neurological deterioration and megaloblastic anemia, and, if left untreated, to death. Subclinical vitamin B12 deficiency (usually defined as a total serum B12 of <200 pmol/L) presents asymptomatically or with rather subtle generic symptoms that oftentimes are mistakenly ascribed to unrelated disorders. Numerous studies have now established that serum vitamin B12 has limited diagnostic value as a stand-alone marker. Low serum levels of vitamin B12 not always represent deficiency, and likewise, severe functional deficiency of the micronutrient has been documented in the presence of normal and even high levels of serum vitamin B12. This review discusses the usefulness and limitations of current biomarkers of B12 status in newborn screening, infant and adult diagnostics, the algorithms utilized to diagnose B12 deficiency and unusual findings of vitamin B12 status in various human disorders.

Prevalence and correlates of patient-centred preparatory information provision to computed tomography and magnetic resonance imaging outpatients: A cross-sectional study.

PubMed

Hyde, Lisa; Mackenzie, Lisa; Boyes, Allison W; Evans, Tiffany-Jane; Symonds, Michael; Sanson-Fisher, Rob

2018-06-02

Responsiveness to information preferences is key to high-quality, patient-centred care. This study examined the top ten preparatory information items not delivered in accordance with medical imaging outpatients' preferences, and patient characteristics associated with reporting a greater number of unmet information preferences. Magnetic resonance imaging and computed tomography outpatients were recruited consecutively in one major public hospital waiting room. Participants self-administered a touchscreen computer questionnaire assessing their sociodemographic and scan characteristics, and unmet preferences for 33 guideline-endorsed preparatory information items. Of 317 eligible patients, 280 (88%) consented to participate. Given equal rankings, the top ten unmet information preferences included 13 items which were endorsed by at least 25% of participants, and commonly related to receiving 'too little' information. One item related to the pre-scan period, seven items to the scan period and five items to the post-scan period. None of the patient characteristics examined were significantly associated with reporting a greater number of unmet information preferences. There is room to improve responsiveness to medical imaging outpatients' preparatory information preferences. Improvements should be targeted at individuals, rather than groups defined by sociodemographic or scan characteristics. A standardised approach to addressing individual patient's information preferences is needed. Copyright © 2018 Elsevier B.V. All rights reserved.

Patient Preferences for Attributes of Multiple Sclerosis Disease-Modifying Therapies

PubMed Central

Loucks, Aimee; Gipson, Gregory; Zhong, Lixian; Bui, Christine; Miller, Elizabeth; Owen, Mary; Pelletier, Daniel; Goodin, Douglas; Waubant, Emmanuelle; McCulloch, Charles E.

2015-01-01

Background: Timely individualized treatment is essential to improving relapsing-remitting multiple sclerosis (RRMS) patient health outcomes, yet little is known about how patients make treatment decisions. We sought to evaluate RRMS patient preferences for risks and benefits of treatment. Methods: Fifty patients with RRMS completed conjoint analysis surveys with 16 hypothetical disease-modifying therapy (DMT) medication profiles developed using a fractional factorial design. Medication profiles were assigned preference ratings from 0 (not acceptable) to 10 (most favorable). Medication attributes included a range of benefits, adverse effects, administration routes, and market durations. Analytical models used linear mixed-effects regression. Results: Participants showed the highest preference for medication profiles that would improve their symptoms (β = 0.81–1.03, P < .001), not a proven DMT outcome. Preventing relapses, the main clinical trial outcome, was not associated with significant preferences (P = .35). Each year of preventing magnetic resonance imaging changes and disease symptom progression showed DMT preferences of 0.17 point (β = 0.17, P = .002) and 0.12 point (β = 0.12, P < .001), respectively. Daily oral administration was preferred over all parenteral routes (P < .001). A 1% increase in death or severe disability decreased relative DMT preference by 1.15 points (P < .001). Conclusions: Patient preference focused on symptoms and prevention of progression but not on relapse prevention, the proven drug outcome. Patients were willing to accept some level of serious risk for certain types and amounts of benefits, and they strongly preferred daily oral administration over all other options. PMID:25892977

Consumer preferences for fresh tomato at the European scale: a common segmentation on taste and firmness.

PubMed

Causse, Mathilde; Friguet, Chloé; Coiret, Clément; Lépicier, Mélanie; Navez, Brigitte; Lee, Monica; Holthuysen, Nancy; Sinesio, Fiorella; Moneta, Elisabetta; Grandillo, Silvana

2010-01-01

Although tomato flavor has not been a major goal for breeders, nowadays it becomes important as it is a subject of consumer complaint. A better knowledge of tomato consumer preferences, at the European level, should provide the basis for improvement of fruit quality and for market segmentation. In the framework of a large European project, 806 consumers from 3 countries, The Netherlands, France, and Italy, were presented with a set of 16 varieties representing the diversity of fresh tomato offer in order to evaluate their preferences. In parallel, sensory profiles were constructed by expert panels in each country. Preference maps were then constructed in each country revealing the structure of consumer preferences and allowing identification of the most important characteristics. Then a global analysis revealed that preferences were quite homogeneous across countries. This study identified the overall flavor and firmness as the most important traits for improving tomato fruit quality. It showed that consumer preferences from different European countries, with different cultures and food practices, are segmented following similar patterns when projected onto a common referential plan. Moreover, the results clearly showed that diversification of taste and texture is required to satisfy all consumers' expectations as some consumers preferred firm tomatoes, while others preferred melting ones and were more or less demanding in terms of sweetness and flavor intensity. Detailed comparisons also showed the importance of the fruit appearance in consumer preference. © 2010 Institute of Food Technologists®

Musculoskeletal Health and Injury Prevention

DTIC Science & Technology

2008-07-01

benefits , from maintaining low back health to preventing knee injury; • Pilates is an alternative approach for treating non-specific low back pain...Omega-3 Fatty Acids • Calcium and Vitamin D • Coenzyme Q10 • Capsaicin Cream ( chili peppers) Summary Musculoskeletal health requires: • A

2-Oxoacid Metabolism in Methanogenic CoM and CoB Biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, David E

Coenzyme M (CoM) and coenzyme B (CoB) are essential for methane production by the euryarchaea that employ this specialized anaerobic metabolism. Two pathways are known to produce CoM, 2-mercaptoethanesulfonate, and both converge on the 2-oxoacid sulfopyruvate. These cells have recruited the rich biochemistry of amino acid and 2-oxoacid metabolizing enzymes to produce a compound that resembles oxaloacetate, but with a more stable and acidic sulfonate group. 7-Mercaptoheptanoylthreonine phosphate, CoB, likewise owes its carbon backbone to a 2-oxoacid. Three enzymes recruited from leucine biosynthesis have evolved to catalyze the elongation of 2-oxoglutarate to 2-oxosuberate in CoB biosynthesis. This chapter describes themore » enzymology, synthesis and analytical techniques used to study 2-oxoacid metabolism in these pathways. Protein structure and mechanistic information from enzymes provides insight into the evolution of new enzymatic activity, and the evolution of substrate specificity from promiscuous enzyme scaffolds.« less

Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells

PubMed Central

Tsuchiya, Yugo; Peak-Chew, Sew Yeu; Newell, Clare; Miller-Aidoo, Sheritta; Mangal, Sriyash; Zhyvoloup, Alexander; Bakovic´, Jovana; Malanchuk, Oksana; Pereira, Gonçalo C.; Kotiadis, Vassilios; Szabadkai, Gyorgy; Duchen, Michael R.; Campbell, Mark; Cuenca, Sergio Rodriguez; Vidal-Puig, Antonio; James, Andrew M.; Murphy, Michael P.; Filonenko, Valeriy; Skehel, Mark

2017-01-01

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions. PMID:28341808

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

PubMed Central

WU, JIANG; JI, FANG; DI, WEN; CHEN, HONGDUO; WAN, YINSHENG

2011-01-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells. PMID:22866118

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death.

PubMed

Wu, Jiang; Ji, Fang; DI, Wen; Chen, Hongduo; Wan, Yinsheng

2011-05-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

Bioavailability enhancement of coenzyme Q10: an extensive review of patents.

PubMed

Beg, Sarwar; Javed, Shamama; Kohli, Kanchan

2010-11-01

Coenzyme Q10 (CoQ10) is a major antioxidant principle found in human body which plays a vital role in maintaining several biochemical pathways of body. It acts as a potential mediator in transferring electrons in oxidoreductive reactions of electron transport chain. Chemically, it is a basic quinone containing moiety having a large and high molecular weight structure. Deficiency of this in body leads to several potential disorders like dysfunctions in cellular energetics, neurological degeneration, higher oxidative stress induced damage, breast cancer etc. The high molecular weight and lipophilicity of CoQ10 makes it poorly water soluble and consequently leads to low systemic availability. Several advancements have been made to enhance the bioavailability of CoQ10 using various approaches like size reduction, solubility enhancement (by solid dispersion, prodrug, complexation, ionization) and use of novel drug carriers such as liposomes, microspheres, nanoparticles, nanoemulsions and self-emulsifying system. The primary objective of the present review is to assemble patents representing the various approaches used for enhancement of CoQ10 bioavailability.

Extracellular ascorbate stabilization as a result of transplasma electron transfer in Saccharomyces cerevisiae.

PubMed

Santos-Ocaña, C; Navas, P; Crane, F L; Córdoba, F

1995-12-01

The presence of yeast cells in the incubation medium prevents the oxidation of ascrobate catalyzed by copper ions. Ethanol increases ascorbate retention. Pyrazole, an alcohol dehydrogenase inhibitor, prevents ascorbate stabilization by cells. Chelation of copper ions does not account for stabilization, since oxidation rates with broken or boiled cells or conditioned media are similar to control rates in the absence of cells. Protoplast integrity is needed to reach optimal values of stabilization. Chloroquine, a known inhibitor of plasma membrane redox systems, inhibits the ascorbate stabilization, the inhibition being partially reversed by coenzyme Q6. Chloroquine does not inhibit ferricyanide reduction. Growth of yeast in iron-deficient media to increase ferric ion reductase activity also increases the stabilization. In conclusion, extracellular ascorbate stabilization by yeast cells can reflect a coenzyme Q dependent transplasmalemma electron transfer which uses NADH as electron donor. Iron deficiency increases the ascorbate stabilization but the transmembrane ferricyanide reduction system can act independently of ascorbate stabilization.

Apparent growth phase-dependent phosphorylation of malonyl coenzyme A:acyl carrier protein transacylase (MCAT), a major fatty acid synthase II component in Mycobacterium bovis BCG.

PubMed

Sinha, Indrajit; Boon, Calvin; Dick, Thomas

2003-10-10

Probing protein extracts from exponentially growing and stationary phase cultures of Mycobacterium bovis BCG with anti-phospho amino acid antibodies revealed a 31-kDa anti-phospho threonine antibody-reactive protein specific to growing culture. The corresponding protein was purified via two-dimensional gel electrophoresis and identified via mass spectrometry to be malonyl coenzyme A:acyl carrier protein transacylase (MCAT), a component of the fatty acid biosynthetic pathway. MCAT tagged with histidine reacted with anti-phospho threonine antibody and was positive in an in-gel chemical assay for phospho proteins. Analysis of the growth phase dependence of MCAT-His phosphorylation and protein levels showed that phosphorylated MCAT-His can be detected only in growing culture. In contrast, MCAT-His protein level was growth phase-independent. These results suggest that MCAT may be a substrate of a protein kinase and phosphatase, and that aspects of fatty acid synthesis in tubercle bacilli are regulated by protein phosphorylation.

Effects of aeration on formation and localization of the acetyl coenzyme A synthetases of Saccharomyces cerevisiae

NASA Technical Reports Server (NTRS)

Klein, H. P.; Jahnke, L.

1979-01-01

Previous studies on the yeast Saccharomyces cerevisiae have shown that two different forms of the enzyme acetyl coenzyme A synthetase (ACS) are present, depending on the conditions under which the cells are grown. The paper evaluates the usefulness of a method designed to assay both synthetases simultaneously in yeast homogenates. The data presented confirm the possibility of simultaneous detection and estimation of the amount of both ACSs of S. cerevisiae in crude homogenates of this strain, making possible the study of physiological factors involved in the formation of these isoenzymes. One important factor for specifying which of the two enzymes is found in these yeast cells is the presence or absence of oxygen in their environment. Aeration not only affects the ratio of the two ACSs but also appears to affect the cellular distribution of these enzymes. Most of the data presented suggest the possibility that the nonaerobic ACS may serve as a precursor to the aerobic form.

(S)-3-hydroxy-3-methylglutaryl coenzyme A reductase, a product of the mva operon of Pseudomonas mevalonii, is regulated at the transcriptional level.

PubMed Central

Wang, Y L; Beach, M J; Rodwell, V W

1989-01-01

We have cloned and sequenced a 505-base-pair (bp) segment of DNA situated upstream of mvaA, the structural gene for (S)-3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88) of Pseudomonas mevalonii. The DNA segment that we characterized includes the promoter region for the mva operon. Nuclease S1 mapping and primer extension analysis showed that mvaA is the promoter-proximal gene of the mva operon. Transcription initiates at -56 bp relative to the first A (+1) of the translation start site. Transcription in vivo was induced by mevalonate. Structural features of the mva promoter region include an 80-bp A + T-rich region, and -12, -24 consensus sequences that resemble sequences of sigma 54 promoters in enteric organisms. The relative amplitudes of catalytic activity, enzyme protein, and mvaA mRNA are consistent with a model of regulation of this operon at the transcriptional level. Images PMID:2477360

Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

PubMed

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-09-01

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

Acyl Coenzyme A Thioesterase 7 Regulates Neuronal Fatty Acid Metabolism To Prevent Neurotoxicity

PubMed Central

Ellis, Jessica M.; Wong, G. William

2013-01-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7N−/−, revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7N−/− mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7N−/− mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity. PMID:23459938

Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

PubMed

Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

2013-05-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

Coenzyme Q10 deficiencies in neuromuscular diseases.

PubMed

Artuch, Rafael; Salviati, Leonardo; Jackson, Sandra; Hirano, Michio; Navas, Plácido

2009-01-01

Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids beta-oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by mutation(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases.

Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria.

PubMed

Faehnle, Christopher R; Le Coq, Johanne; Liu, Xuying; Viola, Ronald E

2006-10-13

Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical branch point transformation in amino acid bio-synthesis. The products of the aspartate pathway are essential in microorganisms, and this entire pathway is absent in mammals, making this enzyme an attractive target for antibiotic development. The first structure of an ASADH from a Gram-positive bacterium, Streptococcus pneumoniae, has now been determined. The overall structure of the apoenzyme has a similar fold to those of the Gram-negative and archaeal ASADHs but contains some interesting structural variations that can be exploited for inhibitor design. Binding of the coenzyme NADP, as well as a truncated nucleotide analogue, into an alternative conformation from that observed in Gram-negative ASADHs causes an enzyme domain closure that precedes catalysis. The covalent acyl-enzyme intermediate was trapped by soaking the substrate into crystals of the coenzyme complex, and the structure of this elusive intermediate provides detailed insights into the catalytic mechanism.

Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies.

PubMed

Ozaltin, Fatih

2014-06-01

Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q10 (CoQ10), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ10 deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ10 in the cell, which is determined by the severity of the mutation. Primary CoQ10 deficiency is unique among mitochondrial disorders because early supplementation with CoQ10 can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ10 deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.

Molecular lego for the assembly of biosensing layers.

PubMed

Mano, N; Kuhn, A

2005-03-31

We propose a procedure to assemble monolayers of redox mediator, coenzyme, enzyme and stabilizing polyelectrolyte on an electrode surface using essentially electrostatic and complexing interactions. In a first step a monolayer of redox mediator, substituted nitrofluorenones, is adsorbed. In a second step, a layer of calcium cations is immobilized at the interface. It establishes a bridge between the redox mediator and the subsequently adsorbed coenzyme NAD(+). In the next step we use the intrinsic affinity of the NAD(+) monolayer for dehydrogenases to build up a multilayer composed of mediator/Ca(2+)/NAD(+)/dehydrogenase. The so obtained modified electrode can be used as a biosensor. Quartz crystal microbalance measurements allowed us to better understand the different parameters responsible for the adsorption. A more detailed investigation of the system made it possible to finally stabilize the assembly sufficiently by the adsorption of a polyelectrolyte layer in order to perform rotating disk electrode measurements with the whole supramolecular architecture on the electrode surface.

Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals

PubMed Central

Atanassov, Ilian; Kuznetsova, Irina; Hinze, Yvonne; Mourier, Arnaud; Filipovska, Aleksandra

2017-01-01

Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment. PMID:29132502

Modeling of process parameters for enhanced production of coenzyme Q10 from Rhodotorula glutinis.

PubMed

Balakumaran, Palanisamy Athiyaman; Meenakshisundaram, Sankaranarayanan

2015-01-01

Coenzyme Q10 (CoQ10) plays an indispensable role in ATP generation through oxidative phosphorylation and helps in scavenging superoxides generated during electron transfer reactions. It finds extensive applications specifically related to oxidative damage and metabolic dysfunctions. This article reports the use of a statistical approach to optimize the concentration of key variables for the enhanced production of CoQ10 by Rhodotorula glutinis in a lab-scale fermenter. The culture conditions that promote optimum growth and CoQ10 production were optimized and the interaction of significant variables para-hydroxybenzoic acid (PHB, 819.34 mg/L) and soybean oil (7.78% [v/v]) was studied using response surface methodology (RSM). CoQ10 production increased considerably from 10 mg/L (in control) to 39.2 mg/L in batch mode with RSM-optimized precursor concentration. In the fed-batch mode, PHB and soybean oil feeding strategy enhanced CoQ10 production to 78.2 mg/L.

Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension.

PubMed

Davis, Benjamin Michael; Tian, Kailin; Pahlitzsch, Milena; Brenton, Jonathan; Ravindran, Nivedita; Butt, Gibran; Malaguarnera, Giulia; Normando, Eduardo M; Guo, Li; Cordeiro, M Francesca

2017-09-01

Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α-tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p<0.05) and Brn3 (p<0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Complementary and alternative medicine approaches to blood pressure reduction: An evidence-based review.

PubMed

Nahas, Richard

2008-11-01

ABSTRACTOBJECTIVETo review the evidence supporting complementary and alternative medicine approaches used in the treatment of hypertension.QUALITY OF EVIDENCEMEDLINE and EMBASE were searched from January 1966 to May 2008 combining the key words hypertension or blood pressure with acupuncture, chocolate, cocoa, coenzyme Q10, ubiquinone, melatonin, vitamin D, meditation, and stress reduction. Clinical trials, prospective studies, and relevant references were included.MAIN MESSAGEEvidence from systematic reviews supports the blood pressure-lowering effects of coenzyme Q10, polyphenol-rich dark chocolate, Qigong, slow breathing, and transcendental meditation. Vitamin D deficiency is associated with hypertension and cardiovascular risk; supplementation lowered blood pressure in 2 trials. Acupuncture reduced blood pressure in 3 trials; in 1 of these it was no better than an invasive placebo. Melatonin was effective in 2 small trials, but caution is warranted in patients taking pharmacotherapy.CONCLUSIONSeveral complementary and alternative medicine therapies can be considered as part of an evidence-based approach to the treatment of hypertension. The potential benefit of these interventions warrants further research using cardiovascular outcomes.

Glycemia, ketonemia, and brain enzymes of ketone body utilization in suckling and adult rats undernourished from intrauterine life.

PubMed

Escrivá, F; Rodríguez, C; Pascual-Leone, A M

1985-05-01

The effect of undernutrition from the 16th day of pregnancy up to 70th day of life on blood glucose and ketone bodies and on several brain mitochondrial enzymes related to energy metabolism or biosynthetic function was investigated. Undernutrition in perinatal period was established by means of a food restriction to pregnant rats and, later, to the lactating mother; undernourished postweaned rats received half the diet consumed by the controls. Body and brain weight from undernourished rats was less than controls throughout the entire period studied. Glycemia and ketonemia were also always lower than controls. Cytochrome c oxidase, citrate synthase, 3-hydroxybutyrate dehydrogenase, 3-oxoacid coenzyme A transferase, and acetoacetyl-coenzyme A thiolase activities during the suckling period were in most stages lower than controls; subsequently, activities in undernourished rats reached or surpassed the control values. These results could explain the "catch up" phenomenon in several ultrastructural parameters found by other authors in undernourished postweaned rats.

Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.

PubMed

Dusi, Sabrina; Valletta, Lorella; Haack, Tobias B; Tsuchiya, Yugo; Venco, Paola; Pasqualato, Sebastiano; Goffrini, Paola; Tigano, Marco; Demchenko, Nikita; Wieland, Thomas; Schwarzmayr, Thomas; Strom, Tim M; Invernizzi, Federica; Garavaglia, Barbara; Gregory, Allison; Sanford, Lynn; Hamada, Jeffrey; Bettencourt, Conceição; Houlden, Henry; Chiapparini, Luisa; Zorzi, Giovanna; Kurian, Manju A; Nardocci, Nardo; Prokisch, Holger; Hayflick, Susan; Gout, Ivan; Tiranti, Valeria

2014-01-02

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Heterogeneity in general practitioners' preferences for quality improvement programs: a choice experiment and policy simulation in France.

PubMed

Ammi, Mehdi; Peyron, Christine

2016-12-01

Despite increasing popularity, quality improvement programs (QIP) have had modest and variable impacts on enhancing the quality of physician practice. We investigate the heterogeneity of physicians' preferences as a potential explanation of these mixed results in France, where the national voluntary QIP - the CAPI - has been cancelled due to its unpopularity. We rely on a discrete choice experiment to elicit heterogeneity in physicians' preferences for the financial and non-financial components of QIP. Using mixed and latent class logit models, results show that the two models should be used in concert to shed light on different aspects of the heterogeneity in preferences. In particular, the mixed logit demonstrates that heterogeneity in preferences is concentrated on the pay-for-performance component of the QIP, while the latent class model shows that physicians can be grouped in four homogeneous groups with specific preference patterns. Using policy simulation, we compare the French CAPI with other possible QIPs, and show that the majority of the physician subgroups modelled dislike the CAPI, while favouring a QIP using only non-financial interventions. We underline the importance of modelling preference heterogeneity in designing and implementing QIPs.

Physicians' Preferences for Communication of Pharmacist-Provided Medication Therapy Management in Community Pharmacy.

PubMed

Guthrie, Kendall D; Stoner, Steven C; Hartwig, D Matthew; May, Justin R; Nicolaus, Sara E; Schramm, Andrew M; DiDonato, Kristen L

2017-02-01

(1) To identify physicians' preferences in regard to pharmacist-provided medication therapy management (MTM) communication in the community pharmacy setting; (2) to identify physicians' perceived barriers to communicating with a pharmacist regarding MTM; and (3) to determine whether Missouri physicians feel MTM is beneficial for their patients. A cross-sectional prospective survey study of 2021 family and general practice physicians registered with MO HealthNet, Missouri's Medicaid program. The majority (52.8%) of physicians preferred MTM data to be communicated via fax. Most physicians who provided care to patients in long-term care (LTC) facilities (81.0%) preferred to be contacted at their practice location as opposed to the LTC facility. The greatest barriers to communication were lack of time and inefficient communication practices. Improved/enhanced communication was the most common suggestion for improvement in the MTM process. Approximately 67% of respondents reported MTM as beneficial or somewhat beneficial for their patients. Survey respondents saw value in the MTM services offered by pharmacists. However, pharmacists should use the identified preferences and barriers to improve their currently utilized communication practices in hopes of increasing acceptance of recommendations. Ultimately, this may assist MTM providers in working collaboratively with patients' physicians.

Further improvement in ganoderic acid production in static liquid culture of Ganoderma lucidum by integrating nitrogen limitation and calcium ion addition.

PubMed

Li, Huan-Jun; Zhang, De-Huai; Han, Li-Liang; Yu, Xuya; Zhao, Peng; Li, Tao; Zhong, Jian-Jiang; Xu, Jun-Wei

2016-01-01

To further improve the ganoderic acid (GA) production, a novel integrated strategy by combining nitrogen limitation and calcium ion addition was developed. The effects of the integrated combination on the content of GA-T (one powerful anticancer compound), their intermediates (squalene and lanosterol) and on the transcription levels of GA biosynthetic genes in G. lucidum fermentation were investigated. The maximum GA-T content with the integrated strategy were 1.87 mg/ 100 mg dry cell weight, which was 2.1-4.2 fold higher than that obtained with either calcium ion addition or nitrogen limitation alone, and it is also the highest record as ever reported in submerged fermentation of G. lucidum. The squalene content was increased by 3.9- and 2.2-fold in this case compared with either individual strategy alone. Moreover, the transcription levels of the GA biosynthetic genes encoding 3-hydroxy-3-methyglutaryl coenzyme A reductase and lanosterol synthase were also up-regulated by 3.3-7.5 and 1.3-2.3 fold, respectively.

Screening Phosphorylation Site Mutations in Yeast Acetyl-CoA Carboxylase Using Malonyl-CoA Sensor to Improve Malonyl-CoA-Derived Product.

PubMed

Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

2018-01-01

Malonyl-coenzyme A (malonyl-CoA) is a critical precursor for the biosynthesis of a variety of biochemicals. It is synthesized by the catalysis of acetyl-CoA carboxylase (Acc1p), which was demonstrated to be deactivated by the phosphorylation of Snf1 protein kinase in yeast. In this study, we designed a synthetic malonyl-CoA biosensor and used it to screen phosphorylation site mutations of Acc1p in Saccharomyces cerevisiae . Thirteen phosphorylation sites were mutated, and a combination of three site mutations in Acc1p, S686A, S659A, and S1157A, was found to increase malonyl-CoA availability. ACC1 S686AS659AS1157A expression also improved the production of 3-hydroxypropionic acid, a malonyl-CoA-derived chemical, compared to both wild type and the previously reported ACC1 S659AS1157A mutation. This mutation will also be beneficial for other malonyl-CoA-derived products.

Start-up performance and granular sludge features of an improved external circulating anaerobic reactor for algae-laden water treatment.

PubMed

Yu, Yaqin; Lu, Xiwu

2017-09-01

The microbial characteristics of granular sludge during the rapid start of an enhanced external circulating anaerobic reactor were studied to improve algae-laden water treatment efficiency. Results showed that algae laden water was effectively removed after about 35 d, and the removal rates of chemical oxygen demand (COD) and algal toxin were around 85% and 92%, respectively. Simultaneously, the gas generation rate was around 380 mL/gCOD. The microbial community structure in the granular sludge of the reactor was complicated, and dominated by coccus and filamentous bacteria. Methanosphaera , Methanolinea , Thermogymnomonas , Methanoregula , Methanomethylovorans , and Methanosaeta were the major microorganisms in the granular sludge. The activities of protease and coenzyme F 420 were high in the granular sludge. The intermittent stirring device and the reverse-flow system were further found to overcome the disadvantage of the floating and crusting of cyanobacteria inside the reactor. Meanwhile, the effect of mass transfer inside the reactor can be accelerated to help give the reactor a rapid start.

Cross-Sectional Data That Explore the Relationship Between Outpatients' Quality of Life and Preferences for Quality Improvement in Oncology Settings.

PubMed

Fradgley, Elizabeth A; Bryant, Jamie; Paul, Christine L; Hall, Alix E; Sanson-Fisher, Robert W; Oldmeadow, Christopher

2016-06-01

This cross-sectional study assessed the association between oncology outpatients' quality improvement preferences and health-related quality of life (HRQoL). Implementation of specific initiatives preferred by patients with lower HRQoL may be a strategic approach to enhancing care for potentially vulnerable patients. English-speaking adults were recruited from five outpatient chemotherapy clinics located in New South Wales, Australia. Using touch screen devices, participants selected up to 25 initiatives that would improve their experiences and completed the Functional Assessment of Cancer Therapy-General (FACT-G) survey. The logistic odds of selecting an initiative according to FACT-G scores were calculated to determine whether preferences were associated with HRQoL after controlling for potential confounders. Of the 411 eligible outpatients approached to participate, 263 (64%) completed surveys. Commonly selected initiatives were up-to-date information on treatment and condition progress (19.8%), access to or information on financial assistance (18.3%), and reduced clinic wait times (17.5%). For those with relatively lower FACT-G scores, the adjusted odds of selecting five initiatives illustrated an increasing trend: convenient appointment scheduling systems (+23% [P = .002]), reduced wait times (+15% [P = .01]), information on medical emergencies (+14% [P = .04]), access to or information on financial assistance (+15% [P = .009]), help to maintain daily living activities (+18% [P = .007]). Two areas of improvement were commonly selected: easily accessible health services and information and support for self-management. Although the results suggest an association between a few quality improvement preferences and HRQoL, a wider spectrum of patient characteristics must be considered when targeting quality improvement to patient subgroups. Copyright © 2016 by American Society of Clinical Oncology.

Wind profiler signal detection improvements

NASA Technical Reports Server (NTRS)

Hart, G. F.; Divis, Dale H.

1992-01-01

Research is described on potential improvements to the software used with the NASA 49.25 MHz wind profiler located at Kennedy Space Center. In particular, the analysis and results are provided of a study to (1) identify preferred mathematical techniques for the detection of atmospheric signals that provide wind velocities which are obscured by natural and man-made sources, and (2) to analyze one or more preferred techniques to demonstrate proof of the capability to improve the detection of wind velocities.

Toxicological Findings of Pilots Involved in Aviation Accidents Operated under 14 CFR Part 135

DTIC Science & Technology

2009-08-01

metoprolol (Lopressor® or Toprol XL®), pravas- tatin (Pravachol®), atorvastatin (Lipitor®), rosuvastatin (Crestor®), amlodipine (Norvasc®), benazepril... atorvastatin , and rosuvastatin are hy- droxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors used in the treatment of high blood cholesterol

Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

EPA Science Inventory

Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

Patient Preferences for Device-Aided Treatments Indicated for Advanced Parkinson Disease.

PubMed

Marshall, Thomas; Pugh, Amy; Fairchild, Angelyn; Hass, Steven

2017-12-01

Effective treatment for advanced Parkinson disease (PD) uncontrolled with oral medication includes device-aided therapies such as deep brain stimulation (DBS) and continuous levodopa-carbidopa infusion to the duodenum via a portable pump. Our objective was to quantify patient preferences for attributes of these device-aided treatments. We administered a Web-enabled survey to 401 patients in the United States. A discrete-choice experiment (DCE) was used to evaluate patients' willingness to accept tradeoffs among efficacy, tolerability, and convenience of alternative treatments. DCE data were analyzed using random-parameters logit. Best-worst scaling (BWS) was used to elicit the relative importance of device-specific attributes. Conditional logit was used to analyze the BWS data. We tested for differences in preferences among subgroups of patients. Improving ability to think clearly was twice as important as a 6-hour-per-day improvement in control of movement symptoms. After controlling for efficacy, treatment delivered via portable infusion pump was preferred over DBS, and both devices were preferred to oral therapy with poor symptom control. Patients were most concerned about device attributes relating to risk of stroke, difficulty thinking, and neurosurgery. Avoiding surgery to insert a wire in the brain was more important than avoiding surgery to insert a tube into the small intestine. Some differences in preferences among subgroups were statistically, but not qualitatively, significant. This study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions. Copyright © 2017. Published by Elsevier Inc.

Knowing One's Lot in Life versus Climbing the Social Ladder: The Formation of Redistributive Preferences in Urban China

ERIC Educational Resources Information Center

Smyth, Russell; Mishra, Vinod; Qian, Xiaolei

2010-01-01

This paper examines, how individual preferences for redistribution in general and redistribution to improve access to education, improve social protection for the poor, reduce income inequality and reduce unemployment depend on beliefs about what determines one's lot in life and self-assessed prospects for climbing the social ladder in urban…

Willingness to Pay Survey for Chesapeake Bay Total ...

EPA Pesticide Factsheets

A stated preference survey to collect data on households’ use of Chesapeake Bay and its watershed, and of their preferences for a variety of water quality improvements likely to follow from pollution reduction programs. The goal of the project is to obtain valuation estimates that can be used to evaluate alternative policies and approaches to improving water in the Chesapeake Bay.

Evaluating the Performance Improvement Preferences of Disability Service Managers: An Exploratory Study Using Gilbert's Behavior Engineering Model

ERIC Educational Resources Information Center

Wooderson, John R.; Cuskelly, Monica; Meyer, Kim A.

2017-01-01

Background: Front-line managers play an important role in managing the performance of staff working in services for people with intellectual disability, but little is known about the practices they prefer to use to improve staff performance and whether these align with what research has shown to be effective. Method: This study comprised two…

Patient preferences for attributes of multiple sclerosis disease-modifying therapies: development and results of a ratings-based conjoint analysis.

PubMed

Wilson, Leslie S; Loucks, Aimee; Gipson, Gregory; Zhong, Lixian; Bui, Christine; Miller, Elizabeth; Owen, Mary; Pelletier, Daniel; Goodin, Douglas; Waubant, Emmanuelle; McCulloch, Charles E

2015-01-01

Timely individualized treatment is essential to improving relapsing-remitting multiple sclerosis (RRMS) patient health outcomes, yet little is known about how patients make treatment decisions. We sought to evaluate RRMS patient preferences for risks and benefits of treatment. Fifty patients with RRMS completed conjoint analysis surveys with 16 hypothetical disease-modifying therapy (DMT) medication profiles developed using a fractional factorial design. Medication profiles were assigned preference ratings from 0 (not acceptable) to 10 (most favorable). Medication attributes included a range of benefits, adverse effects, administration routes, and market durations. Analytical models used linear mixed-effects regression. Participants showed the highest preference for medication profiles that would improve their symptoms (β = 0.81-1.03, P < .001), not a proven DMT outcome. Preventing relapses, the main clinical trial outcome, was not associated with significant preferences (P = .35). Each year of preventing magnetic resonance imaging changes and disease symptom progression showed DMT preferences of 0.17 point (β = 0.17, P = .002) and 0.12 point (β = 0.12, P < .001), respectively. Daily oral administration was preferred over all parenteral routes (P < .001). A 1% increase in death or severe disability decreased relative DMT preference by 1.15 points (P < .001). Patient preference focused on symptoms and prevention of progression but not on relapse prevention, the proven drug outcome. Patients were willing to accept some level of serious risk for certain types and amounts of benefits, and they strongly preferred daily oral administration over all other options.

Improving the palatability of activated charcoal in pediatric patients.

PubMed

Cheng, Adam; Ratnapalan, Savithiri

2007-06-01

To compare the taste preference and ease of swallowing of activated charcoal among healthy teenagers when mixed separately with 3 different additives: chocolate milk, Coca-Cola, and water. Healthy volunteers between 14 to 19 years of age were selected for the study. Five grams of activated charcoal (25 mL of 0.2 g/mL of Charcodote [Pharma Science, Montreal, Canada]) was mixed with 25 mL of chocolate milk, Coca-Cola, or water individually to make up 50 mL. The volunteers drank the 3 cups of the charcoal-additive mixture separately and then rated taste and ease of swallowing on a 10-cm visual analogue scale. The subjects then indicated their preferred charcoal-additive mixture if he/she had to drink 9 more portions of charcoal (this would estimate the dose of charcoal for a 50-kg child). A total of 44 subjects were recruited (25 boys and 19 girls). The mean scores for taste preference for chocolate milk, Coca-Cola, and water mixtures of charcoal were 5.5, 6.3, and 2.0, respectively, on a 10-cm visual analogue scale. Thus, subjects preferred the taste of charcoal mixed with chocolate milk or Coca-Cola over charcoal mixed with water (P = 0.0003 for both comparisons). The subjects did not show a statistically significant difference for ease of swallowing between the 3 charcoal-additive mixtures. Overall, 48% preferred the chocolate milk mixture, 45% preferred the Coca-Cola mixture, and 7% preferred charcoal mixed with water. Healthy teenaged subjects identified that activated charcoal (Charcodote) mixed with chocolate milk or Coca-Cola (in a 1:1 ratio) improved taste but had no significant effect on improving ease of swallowing. Overall, the addition of chocolate milk or coke improves the palatability of charcoal and is favored over charcoal mixed with water alone.

Do we prescribe what patients prefer? Pilot study to assess patient preferences for medication regimen characteristics.

PubMed

Witticke, Diana; Seidling, Hanna Marita; Klimm, Hans-Dieter; Haefeli, Walter Emil

2012-01-01

The aim of this pilot study was to evaluate patients' self-reported attitudes towards medication-related factors known to impair adherence and to assess their prevalence in ambulatory care as an essential prerequisite to improve patient adherence. We conducted a face-to-face interview with 110 primary care patients maintained on at least one drug. For each drug, the patient was asked to specify medication-related factors of interest, ie, dosage form, dosage interval, required relationship with food intake, and the planned time of day for intake, and to rate the individual relevance of each prevalent parameter on a three-point Likert scale (discriminating between prefer, neutral, and dislike). Tablets with a once-daily dosage frequency were the most preferred dosage form, with a high prevalence in the ambulatory setting. Drug intake in the morning and evening were most preferred, and drug intake at noon was least preferred, but also had a low prevalence in contrast with drug intake independent of meals that was most preferred. Interestingly, only one quarter (26.4%) of all the patients were able to indicate clear preferences or dislikes. When patients are asked to specify their preferences for relevant medication regimen characteristics, they clearly indicated regimens that have been associated with better adherence in earlier studies. Therefore, our results suggest that adaptation of drug regimens to individual preferences might be a promising strategy to improve adherence. Because the German health care system may differ from other systems in relevant aspects, our findings should be confirmed by evaluation of patient preferences in other health care systems. Once generalizability of the study results is shown, these findings could be a promising basis upon which to promote patient adherence right from the beginning of drug therapy.

Modeling the Mental Health Practice Change Preferences of Educators: A Discrete-Choice Conjoint Experiment.

PubMed

Cunningham, Charles E; Barwick, Melanie; Short, Kathy; Chen, Yvonne; Rimas, Heather; Ratcliffe, Jenna; Mielko, Stephanie

2014-01-01

Schools are sometimes slow to adopt evidence-based strategies for improving the mental health outcomes of students. This study used a discrete-choice conjoint experiment to model factors influencing the decision of educators to adopt strategies for improving children's mental health outcomes. A sample of 1,010 educators made choices between hypothetical mental health practice change strategies composed by systematically varying the four levels of 16 practice change attributes. Latent class analysis yielded two segments with different practice change preferences. Both segments preferred small-group workshops, conducted by engaging experts, teaching skills applicable to all students. Participants expressed little interest in Internet options. The support of colleagues, administrators, and unions exerted a strong influence on the practice change choices of both segments. The Change Ready segment, 77.1 % of the sample, was more intent on adopting new strategies to improve the mental health of students. They preferred that schools, rather than the provincial ministry of education, make practice change decisions, coaching was provided to all participants, and participants received post-training follow-up sessions. The Demand Sensitive segment (22.9 %) was less intent on practice change. They preferred that individual teachers make practice change decisions, recommended discretionary coaching, and chose no post-training follow-up support. This study emphasizes the complex social, organizational, and policy context within which educators make practice change decisions. Efforts to disseminate strategies to improve the mental health outcomes of students need to be informed by the preferences of segments of educators who are sensitive to different dimensions of the practice change process. In the absence of a broad consensus of educators, administrators, and unions, potentially successful practice changes are unlikely to be adopted.

An Improved Graph Model for Conflict Resolution Based on Option Prioritization and Its Application

PubMed Central

Yin, Kedong; Li, Xuemei

2017-01-01

In order to quantitatively depict differences regarding the preferences of decision makers for different states, a score function is proposed. As a foundation, coalition motivation and real-coalition analysis are discussed when external circumstance or opportunity costs are considering. On the basis of a confidence-level function, we establish the score function using a “preference tree”. We not only measure the preference for each state, but we also build a collation improvement function to measure coalition motivation and to construct a coordinate system in which to analyze real-coalition stability. All of these developments enhance the applicability of the graph model for conflict resolution (GMCR). Finally, an improved GMCR is applied in the “Changzhou Conflict” to demonstrate how it can be conveniently utilized in practice. PMID:29077049

An Improved Graph Model for Conflict Resolution Based on Option Prioritization and Its Application.

PubMed

Yin, Kedong; Yu, Li; Li, Xuemei

2017-10-27

In order to quantitatively depict differences regarding the preferences of decision makers for different states, a score function is proposed. As a foundation, coalition motivation and real-coalition analysis are discussed when external circumstance or opportunity costs are considering. On the basis of a confidence-level function, we establish the score function using a "preference tree". We not only measure the preference for each state, but we also build a collation improvement function to measure coalition motivation and to construct a coordinate system in which to analyze real-coalition stability. All of these developments enhance the applicability of the graph model for conflict resolution (GMCR). Finally, an improved GMCR is applied in the "Changzhou Conflict" to demonstrate how it can be conveniently utilized in practice.

Ecological influences on individual differences in color preference.

PubMed

Schloss, Karen B; Hawthorne-Madell, Daniel; Palmer, Stephen E

2015-11-01

How can the large, systematic differences that exist between individuals' color preferences be explained? The ecological valence theory (Palmer & Schloss, Proceedings of the National Academy of Sciences 107:8877-8882, 2010) posits that an individual's preference for each particular color is determined largely by his or her preferences for all correspondingly colored objects. Therefore, individuals should differ in their color preferences to the extent that they have different preferences for the same color-associated objects or that they experience different objects. Supporting this prediction, we found that individuals' color preferences were predicted better by their own preferences for correspondingly colored objects than by other peoples' preferences for the same objects. Moreover, the fit between color preferences and affect toward the colored objects was reliably improved when people's own idiosyncratic color-object associations were included in addition to a standard set of color-object associations. These and related results provide evidence that individual differences in color preferences are reliably influenced by people's personal experiences with colored objects in their environment.

Ribose in the heart.

PubMed

Herrick, James; St Cyr, John

2008-01-01

Every cell needs energy, i.e., adenosine triphosphate (ATP), to carry out its function. Decreased oxygen levels, decreased blood flow, and other stressful conditions can drastically effect the intracellular concentrations of these energy compounds. Skeletal muscle, unlike the heart, can address this drop in ATP by employing the myokinase reaction, ultimately producing ATP with a subsequent elevation in adenosine monophosphate (AMP). Ribose, a naturally occurring 5-carbon monosaccharide, is a key component of RNA, DNA (which has deoxyribose), acetyl coenzyme A, and ATP. Each cell produces its own ribose, involved in the pentose phosphate pathway (PPP), to aid in ATP production. States of ischemia and/or hypoxia can severely lower levels of cellular energy compounds in the heart, with an associated compromise in cellular processes, ultimately reflected in altered function. Ribose appears to provide a solution to the problem in replenishing the depressed ATP levels and improving functional status of patients afflicted with cardiovascular diseases.

Oleoyl Coenzyme A Regulates Interaction of Transcriptional Regulator RaaS (Rv1219c) with DNA in Mycobacteria*

PubMed Central

Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin; Mukamolova, Galina V.

2014-01-01

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria. PMID:25012658

Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria.

PubMed

Turapov, Obolbek; Waddell, Simon J; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A; Tudo, Griselda; Labesse, Gilles; Young, Danielle I; Young, Michael; Andrew, Peter W; Butcher, Philip D; Cohen-Gonsaud, Martin; Mukamolova, Galina V

2014-09-05

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of HIBCH gene mutations causing autosomal recessive Leigh syndrome: a gene involved in valine metabolism.

PubMed

Soler-Alfonso, Claudia; Enns, Gregory M; Koenig, Mary Kay; Saavedra, Heather; Bonfante-Mejia, Eliana; Northrup, Hope

2015-03-01

Leigh syndrome is a progressive neurodegenerative disorder with usual onset of symptoms during the first year of life. The disorder has been associated with mutations in over 30 genes. This difficulty with genetic heterogeneity makes whole exome sequencing a more cost-effective approach for investigation of etiology. We describe an individual with typical Leigh syndrome who was found to have compound heterozygous mutations in the gene HIBCH (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism of valine. She exhibited significant clinical improvement after a valine-restricted diet. A subset of patients with uncharacterized Leigh syndrome present with specific biochemical abnormalities. This report highpoints the challenges and restrictions of routine metabolic testing and features the recognition of inborn errors of metabolism as potential treatable causes of Leigh syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

THE EFFECTS OF IONIZING RADIATIONS ON THE BIOCHEMISTRY OF MAMMALIAN TISSUES.

DTIC Science & Technology

Contents: The effects of Ionizing Radiations on the Biochemistry of Mammalian Tissues: (1) Studies on the Effect of X-irradiation on Coenzyme A ... Levels of the Livers of Mice; (2) Influence of X-irradiation on the Development of a Detoxification System for Phosphorothioates in the Livers of Rats

Molecular survey of turfgrass species for mutations conferring resistance to ACCase inhibiting herbicides

USDA-ARS?s Scientific Manuscript database

The control of grassy weeds in turfgrass is often problematic due to lack of herbicide selectivity. Seven different naturally occurring mutation sites have been reported to confer resistance to Acetyl coenzyme A carboxylase inhibiting herbicides. One or more of these mutation sites may hold potentia...

Comparison of different supplemental cobalt forms on fiber digestion and cobalamin levels

USDA-ARS?s Scientific Manuscript database

Cobalt (Co) is essential for rumen microbial metabolism to synthesize methane, acetate and methionine. It also serves as a structural component of vitamin B*12, which functions as a coenzyme in energy metabolism. A study was conducted to determine if Co form (cobalt carbonate vs cobalt glucoheptona...

Comparison of supplemental cobalt form on fibre digestion and cobalamin concentrations in cattle

USDA-ARS?s Scientific Manuscript database

Cobalt is essential for rumen microbial metabolism to synthesize methane, acetate and methionine. It also serves as a structural component of vitamin B12, which functions as a coenzyme in energy metabolism. A study was conducted to determine if cobalt form (cobalt carbonate vs cobalt glucoheptonate...

Comparison of different supplemental cobalt forms on digestion and cobalamin levels

USDA-ARS?s Scientific Manuscript database

Cobalt (Co) is essential for rumen microbial metabolism to synthesize methane, acetate and methionine. It also serves as a structural component of vitamin B12, which functions as a coenzyme in energy metabolism. A study was conducted to determine if Co form (cobalt carbonate vs cobalt glucoheptonat...

Effects of contour enhancement on low-vision preference and visual search.

PubMed

Satgunam, Premnandhini; Woods, Russell L; Luo, Gang; Bronstad, P Matthew; Reynolds, Zachary; Ramachandra, Chaithanya; Mel, Bartlett W; Peli, Eli

2012-09-01

To determine whether image enhancement improves visual search performance and whether enhanced images were also preferred by subjects with vision impairment. Subjects (n = 24) with vision impairment (vision: 20/52 to 20/240) completed visual search and preference tasks for 150 static images that were enhanced to increase object contours' visual saliency. Subjects were divided into two groups and were shown three enhancement levels. Original and medium enhancements were shown to both groups. High enhancement was shown to group 1, and low enhancement was shown to group 2. For search, subjects pointed to an object that matched a search target displayed at the top left of the screen. An "integrated search performance" measure (area under the curve of cumulative correct response rate over search time) quantified performance. For preference, subjects indicated the preferred side when viewing the same image with different enhancement levels on side-by-side high-definition televisions. Contour enhancement did not improve performance in the visual search task. Group 1 subjects significantly (p < 0.001) rejected the High enhancement, and showed no preference for medium enhancement over the original images. Group 2 subjects significantly preferred (p < 0.001) both the medium and the low enhancement levels over original. Contrast sensitivity was correlated with both preference and performance; subjects with worse contrast sensitivity performed worse in the search task (ρ = 0.77, p < 0.001) and preferred more enhancement (ρ = -0.47, p = 0.02). No correlation between visual search performance and enhancement preference was found. However, a small group of subjects (n = 6) in a narrow range of mid-contrast sensitivity performed better with the enhancement, and most (n = 5) also preferred the enhancement. Preferences for image enhancement can be dissociated from search performance in people with vision impairment. Further investigations are needed to study the relationships between preference and performance for a narrow range of mid-contrast sensitivity where a beneficial effect of enhancement may exist.

Stated Preference Survey Estimating the Willingness to Pay ...

EPA Pesticide Factsheets

A national stated preference survey designed to elicit household willingness to pay for reductions in impinged and entrained fish at cooling water intake structures. To improve estimation of environmental benefits estimation

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

PubMed

Liu, Jiankang

2008-01-01

We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

Employment preferences of public sector nurses in Malawi: results from a discrete choice experiment.

PubMed

Mangham, Lindsay J; Hanson, Kara

2008-12-01

To understand the employment preferences of Malawian public sector registered nurses, and to ascertain whether salary increases significantly affect how nurses regard their employment. A discrete choice experiment was used to assess the significance of six job attributes on nurses' preferences over pairs of job descriptions: net monthly pay, provision of government housing, opportunities to upgrade their qualifications, typical workload, availability of resources and place of work. A multivariate model was used to estimate the extent to which nurses were willing to trade between their monetary benefits, non-monetary benefits, and working conditions, and to determine the relative importance of the job attributes. Most nurses were willing to trade among attributes, and very few appeared to have preferences that were dominated by a single job attribute. All attributes had a statistically significant influence on nurses' preferences, and further analysis showed the rate at which they were willing to forego pay increases for other improvements in their employment conditions. Opportunities to upgrade professional qualifications, government housing and the increases in net monthly pay had the greatest impact on nurses' employment choices. Salary enhancement can improve the motivation and retention of nurses, as well as improvements of employment conditions, which support existing efforts to address the health worker shortage.

THE EFFECT OF ANIMAL MATURITY AND FAT DISTRIBUTION ON THE QUALITY OF IRRADIATED BEEF. Report No. 7 (Final), September 6, 1957-June 30, 1960

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henrickson, R.L.

1961-10-31

The effects of animal maturity and fat distribution on the quality of irradiated beef were investigated. For ground beef the preference ratings decressed as the irrsdiation dose increassd. When the meat was stored at 40 deg F, those samples treated with low doses of irradiation quickly decreased in preference. Meat treated with 0.5 megarad of gamma radiation had little irradiation flavor change. Ground meat from animals slaughtered at 12 months of age was generally preferred, followed by products from 24 and 6 month old animals. Altering the fat content of the ground meat caused some change in eating preference ofmore » the irradiated product during storage. Meat of low fat content from animals slaughtered at 12 months of age was generally preferred. For steak, shear and taste panel values indicated that some tenderness variation does exist among animals. Flavor and texture difference also occurred among beef muscles. Aging the meat 14 days prior to being irradiated did not greatly improve the flavor. An irradiation treatment was found to improve the tenderness of hoth the semitendinosus and longissimus dorsi muscles. No improvement in flavor, arorua, or texture was observed when beef was irradiated prior to the on-set of rigor. (auth)« less

Eliciting population preferences for mass colorectal cancer screening organization.

PubMed

Nayaradou, Maximilien; Berchi, Célia; Dejardin, Olivier; Launoy, Guy

2010-01-01

The implementation of mass colorectal cancer (CRC) screening is a public health priority. Population participation is fundamental for the success of CRC screening as for any cancer screening program. The preferences of the population may influence their likelihood of participation. The authors sought to elicit population preferences for CRC screening test characteristics to improve the design of CRC screening campaigns. A discrete choice experiment was used. Questionnaires were compiled with a set of pairs of hypothetical CRC screening scenarios. The survey was conducted by mail from June 2006 to October 2006 on a representative sample of 2000 inhabitants, aged 50 to 74 years from the northwest of France, who were randomly selected from electoral lists. Questionnaires were sent to 2000 individuals, each of whom made 3 or 4 discrete choices between hypothetical tests that differed in 7 attributes: how screening is offered, process, sensitivity, rate of unnecessary colonoscopy, expected mortality reduction, method of screening test result transmission, and cost. Complete responses were received from 656 individuals (32.8%). The attributes that influenced population preferences included expected mortality reduction, sensitivity, cost, and process. Participants from high social classes were particularly influenced by sensitivity. The results demonstrate that the discrete choice experiment provides information on patient preferences for CRC screening: improving screening program effectiveness, for instance, by improving test sensitivity (the most valued attribute) would increase satisfaction among the general population with regard to CRC screening programs. Additional studies are required to study how patient preferences actually affect adherence to regular screening programs.

Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.

PubMed

Banach, Maciej; Serban, Corina; Sahebkar, Amirhossein; Ursoniu, Sorin; Rysz, Jacek; Muntner, Paul; Toth, Peter P; Jones, Steven R; Rizzo, Manfredi; Glasser, Stephen P; Lip, Gregory Y H; Dragan, Simona; Mikhailidis, Dimitri P

2015-01-01

To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to μkat/L, multiply by 0.0167]; 95% CI, -14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, -0.53; 95% CI, -1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, -0.001; 95% CI, -0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, -0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

PubMed Central

2014-01-01

Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.

PubMed

Gobin-Limballe, S; Djouadi, F; Aubey, F; Olpin, S; Andresen, B S; Yamaguchi, S; Mandel, H; Fukao, T; Ruiter, J P N; Wanders, R J A; McAndrew, R; Kim, J J; Bastin, J

2007-12-01

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an inborn mitochondrial fatty-acid beta-oxidation (FAO) defect associated with a broad mutational spectrum, with phenotypes ranging from fatal cardiopathy in infancy to adolescent-onset myopathy, and for which there is no established treatment. Recent data suggest that bezafibrate could improve the FAO capacities in beta-oxidation-deficient cells, by enhancing the residual level of mutant enzyme activity via gene-expression stimulation. Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, we investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblasts representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 h) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. This pattern of response was not due to differential inductions of VLCAD messenger RNA, as shown by quantitative real-time polymerase chain reaction, but reflected variable increases in measured VLCAD residual enzyme activity in response to bezafibrate. Genotype cross-analysis allowed the identification of alleles carrying missense mutations, which could account for these different pharmacological profiles and, on this basis, led to the characterization of 9 mild and 11 severe missense mutations. Altogether, the responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype, thus providing a new approach for analysis of genetic heterogeneity. Finally, this study emphasizes the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy.

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q(10) in elderly men and women.

PubMed

Yubero-Serrano, Elena M; Gonzalez-Guardia, Lorena; Rangel-Zuñiga, Oriol; Delgado-Casado, Nieves; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Caballero, Javier; Marin, Carmen; Gutierrez-Mariscal, Francisco M; Tinahones, Francisco J; Villalba, Jose M; Tunez, Isaac; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2013-02-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid-rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells.

Matching services with local preferences: managing primary education services in a rural district of India.

PubMed

Subrahmanian, R

1999-02-01

India's poorest households have particularly little access to education. Urgent reforms are therefore needed to improve the universal availability of quality basic services and universal access to those services. At least 32 million children in India are estimated to not be enrolled and attending school. These children must be brought into schools in order to meet the goal of Universal Elementary Education (UEE). Widespread support exists for the decentralization of public services due to the equity and efficiency benefits associated with it. In particular, decentralization is seen to facilitate the matching of services with local preferences, increasing the chances of meeting policy goals. This approach is explored in the context of research conducted in a village of Raichur district, where poor households' preferences with regard to school timing are analyzed. Sections consider the equity and efficiency merits of decentralization, the agenda for improving education service delivery in India, users' relationship to the education system in Raichur district, how preferences are revealed, whose preferences are important in the conflict between local and policy perspectives, preference heterogeneity in the village context, and whether aspects of education services can be selectively decentralized.

Improving uptake and engagement with child body image interventions delivered to mothers: Understanding mother and daughter preferences for intervention content.

PubMed

Garbett, Kirsty M; Diedrichs, Phillippa C

2016-12-01

Mothers are a key influence on adolescent girls' body image. This study aimed to improve understanding of mothers' and daughters' preferences for content in body image interventions designed to assist mothers to promote positive body image among their daughters. British mother-daughter dyads (N=190) viewed descriptions of five evidence-based influences on body image (family, friends, and relationships; appearance-based teasing; media and celebrities; appearance conversations; body acceptance and care). Mothers and daughters each selected the two most important influences to learn about in these interventions. Overall, both mothers and daughters most frequently opted for family, friends, and relationships and body acceptance and care, whereas media and celebrities was their least preferred topic. While the overall sample of mothers and daughters agreed on preferences, Fisher's exact tests showed that within-dyad agreement was low. Recommendations for improving parent and child engagement with, and effectiveness of, child body image interventions delivered to parents are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patients' Preferences Related to Benefits, Risks, and Formulations of Schizophrenia Treatment.

PubMed

Levitan, Bennett; Markowitz, Michael; Mohamed, Ateesha F; Johnson, F Reed; Alphs, Larry; Citrome, Leslie; Bridges, John F P

2015-07-01

The objective of this study was to quantify patients' preferences related to benefits and risks of antipsychotic treatments for schizophrenia and to assess the relative importance of treatment attributes and adherence. Treatment-related preferences among U.S. residents with a self-reported physician diagnosis of schizophrenia were assessed via a discrete-choice experiment. Patients chose between competing hypothetical scenarios characterized by improvements in positive symptoms, negative symptoms, and social functioning; incidence of weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia; and medication formulation. Preferences were estimated by using a random-parameters logit model, and the impact of adherence was estimated with conditional logit models. The final sample consisted of 271 patients. Complete improvement in positive symptoms was the most preferred outcome (relative importance score of 10.0), followed by elimination of hyperglycemia (3.6, 95% confidence interval [CI]=2.6-4.6), improvement in negative symptoms (3.0, CI=1.6-4.3), reduced weight gain (2.6, CI=1.2-4.0), avoidance of hyperprolactinemia (1.7, CI=.9-2.6), improved social functioning (1.5, CI=.4-2.5), and avoidance of EPS (1.0, CI=.3-1.8). Patients judged a daily pill superior to monthly injections (p<.01) and monthly injections superior to injections every three months (p<.01) for adherent patients and monthly injections superior to a daily pill for nonadherent patients (p=.01). Persons who self-identified as having schizophrenia judged improvement in positive symptoms as the most important treatment benefit. Hyperglycemia was identified as the most important adverse event. Patients judged oral formulations to be better than monthly injections for adherent patients and monthly injections to be a better choice for nonadherent patients.

A fuzzy set preference model for market share analysis

NASA Technical Reports Server (NTRS)

Turksen, I. B.; Willson, Ian A.

1992-01-01

Consumer preference models are widely used in new product design, marketing management, pricing, and market segmentation. The success of new products depends on accurate market share prediction and design decisions based on consumer preferences. The vague linguistic nature of consumer preferences and product attributes, combined with the substantial differences between individuals, creates a formidable challenge to marketing models. The most widely used methodology is conjoint analysis. Conjoint models, as currently implemented, represent linguistic preferences as ratio or interval-scaled numbers, use only numeric product attributes, and require aggregation of individuals for estimation purposes. It is not surprising that these models are costly to implement, are inflexible, and have a predictive validity that is not substantially better than chance. This affects the accuracy of market share estimates. A fuzzy set preference model can easily represent linguistic variables either in consumer preferences or product attributes with minimal measurement requirements (ordinal scales), while still estimating overall preferences suitable for market share prediction. This approach results in flexible individual-level conjoint models which can provide more accurate market share estimates from a smaller number of more meaningful consumer ratings. Fuzzy sets can be incorporated within existing preference model structures, such as a linear combination, using the techniques developed for conjoint analysis and market share estimation. The purpose of this article is to develop and fully test a fuzzy set preference model which can represent linguistic variables in individual-level models implemented in parallel with existing conjoint models. The potential improvements in market share prediction and predictive validity can substantially improve management decisions about what to make (product design), for whom to make it (market segmentation), and how much to make (market share prediction).

The Development and Public Health Implications of Food Preferences in Children

PubMed Central

Beckerman, Jacob P.; Alike, Queen; Lovin, Erika; Tamez, Martha; Mattei, Josiemer

2017-01-01

Food preferences are a primary determinant of dietary intake and behaviors, and they persist from early childhood into later life. As such, establishing preferences for healthy foods from a young age is a promising approach to improving diet quality, a leading contributor to cardiometabolic health. This narrative review first describes the critical period for food preference development starting in utero and continuing through early childhood. Infants’ innate aversion to sour and bitter tastes can lead them to initially reject some healthy foods such as vegetables. Infants can learn to like these foods through exposures to their flavors in utero and through breastmilk. As solid foods are introduced through toddlerhood, children’s food preferences are shaped by parent feeding practices and environmental factors such as food advertising. Next, we discuss two key focus areas to improve diet quality highlighted by the current understanding of food preferences: (1) promoting healthy food preferences through breastfeeding and early exposures to healthy foods and (2) limiting the extent to which innate preferences for sweet and salty tastes lead to poor diet quality. We use an ecological framework to summarize potential points of intervention and provide recommendations for these focus areas, such as worksite benefits that promote breastfeeding, and changes in food retail and service environments. Individuals’ choices around breastfeeding and diet may ultimately be influenced by policy and community-level factors. It is thus crucial to take a multilevel approach to establish healthy food preferences from a young age, which have the potential to translate into lifelong healthy diet. PMID:29326942

Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

PubMed

Xu, Yangying; Nisenblat, Victoria; Lu, Cuiling; Li, Rong; Qiao, Jie; Zhen, Xiumei; Wang, Shuyu

2018-03-27

Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease.

PubMed

Polyak, Erzsebet; Ostrovsky, Julian; Peng, Min; Dingley, Stephen D; Tsukikawa, Mai; Kwon, Young Joon; McCormack, Shana E; Bennett, Michael; Xiao, Rui; Seiler, Christoph; Zhang, Zhe; Falk, Marni J

2018-04-01

Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials. Here, lifespan effects of N-acetylcysteine (NAC), vitamin E, vitamin C, coenzyme Q10 (CoQ10), mitochondrial-targeted CoQ10 (MS010), lipoate, and orotate were evaluated as the primary outcome in a well-established, short-lived C. elegans gas-1(fc21) animal model of RC complex I disease. Healthspan effects were interrogated to assess potential reversal of their globally disrupted in vivo mitochondrial physiology, transcriptome profiles, and intermediary metabolic flux. NAC or vitamin E fully rescued, and coenzyme Q, lipoic acid, orotic acid, and vitamin C partially rescued gas-1(fc21) lifespan toward that of wild-type N2 Bristol worms. MS010 and CoQ10 largely reversed biochemical pathway expression changes in gas-1(fc21) worms. While nearly all drugs normalized the upregulated expression of the "cellular antioxidant pathway", they failed to rescue the mutant worms' increased in vivo mitochondrial oxidant burden. NAC and vitamin E therapeutic efficacy were validated in human fibroblast and/or zebrafish complex I disease models. Remarkably, rotenone-induced zebrafish brain death was preventable partially with NAC and fully with vitamin E. Overall, these pre-clinical model animal data demonstrate that several classical antioxidant drugs do yield significant benefit on viability and survival in primary mitochondrial disease, where their major therapeutic benefit appears to result from targeting global cellular, rather than intramitochondria-specific, oxidative stress. Clinical trials are needed to evaluate whether the two antioxidants, NAC and vitamin E, that show greatest efficacy in translational model animals significantly improve the survival, function, and feeling of human subjects with primary mitochondrial RC disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Prospective Evaluation of Patient Usage of Above and Below Threshold Waveforms With Traditional Spinal Cord Stimulation Devices.

PubMed

Owusu, Stephanie; Huynh, Alexander; Gruenthal, Eric; Prusik, Julia; Owusu-Sarpong, Stephane; Cherala, Rasan; Peng, Sophia; Pilitsis, Julie G; McCallum, Sarah E

2017-08-01

Spinal cord stimulation (SCS) is an efficacious therapy used to treat chronic pain. The type of SCS programming is important in improving patients' quality of life and overall satisfaction. In this study, 19 patients who underwent SCS with traditional devices were given between 4 and 6 programs including programs with stimulation below sensory threshold and above sensory threshold. Usage patterns and preferences were assessed. SCS patients were given 4-6 programs, some above sensory threshold and some below threshold immediately postoperatively after permanent implantation. Usage patterns of different programs were documented, including percent of time that the settings were used and preference for above threshold vs. below threshold settings during sleeping, walking, sitting, and vigorous activity. Improvements at three months in Oswestry disability index (ODI), numeric rating scale (NRS), Beck depression inventory (BDI), McGill pain questionnaire (MPQ), pain catastrophizing scale (PCS), insomnia severity index (ISI), and Epworth sleepiness scale (ESS) were evaluated. Patients were all trialed on above sensory threshold programs. Six weeks after implantation, most patients preferred above threshold stimulation (74%) vs. below threshold waveforms (21%). Patient diagnosis, type/location of lead or recharging burden played no role in patient preference. Above threshold patients had significantly better improvement in BDI scores than did below threshold patients (p < 0.05) at three-month follow-up but also had worse ESS scores (p < 0.05). Above threshold stimulation was preferred for walking and sitting (p < 0.05). Results indicate that when given the option between waveforms inducing paresthesias and those that do not, SCS patients tend to prefer waveforms that induce paresthesias. Among users of above threshold waveforms, there was preference for these settings during walking and sitting. There was a trend for below threshold preference in vigorous activity and sleeping. © 2017 International Neuromodulation Society.

A Patient-Centered, Provider-Facilitated Approach to the Refinement of Nonlinear Frequency Compression Parameters Based on Subjective Preference Ratings of Amplified Sound Quality.

PubMed

Johnson, Earl E; Light, Keri C

2015-09-01

To evaluate sound quality preferences of participants wearing hearing aids with different strengths of nonlinear frequency compression (NFC) processing versus no NFC processing. Two analysis methods, one without and one with a qualifier as to the magnitude of preferences, were compared for their percent agreement to differentiate a small difference in perceived sound quality as a result of applied NFC processing. A single-blind design was used with participants unaware of the presence or strength of NFC processing (independent variable). The National Acoustic Laboratories-Nonlinear 2 (NAL-NL2) prescription of amplification was chosen because audibility is intentionally not prescribed in the presence of larger sensorineural hearing loss thresholds. A lack of prescribed audibility, when present, was deemed an objective qualifier for NFC. NFC is known to improve the input bandwidth available to listeners when high-frequency audibility is not otherwise available and increasing strengths of NFC were examined. Experimental condition 3 (EC3) was stronger than the manufacturer default (EC2). More aggressive strengths (e.g., EC4 and EC5), however, were expected to include excessive distortion and even reduce the output bandwidth that had been prescribed as audible by NAL-NL2 (EC1). A total of 14 male Veterans with severe high-frequency sensorineural hearing loss. Participant sound quality preference ratings (dependent variable) without a qualifier as to the magnitude of preference were analyzed based on binomial probability theory, as is traditional with paired comparison data. The ratings with a qualifier as to the magnitude of preference were analyzed based on the nonparametric statistic of the Wilcoxon signed rank test. The binomial probability analysis method identified a sound quality preference as well as the nonparametric probability test method. As the strength of NFC increased, more participants preferred the EC with less NFC. Fourteen of 14 participants showed equal preference between EC1 and EC2 perhaps, in part, because EC2 showed no objective improvement in audibility for six of the 14 participants (42%). Thirteen of the 14 participants showed no preference between NAL-NL2 and EC3, but all participants had an objective improvement in audibility. With more NFC than EC3, more and more participants preferred the other EC with less NFC in the paired comparison. By referencing the recommended sensation levels of amplitude compression (e.g., NAL-NL2) in the ear canal of hearing aid wearers, the targeting of NFC parameters can likely be optimized with respect to improvements in effective audibility that may contribute to speech recognition without adversely impacting sound quality. After targeting of NFC parameters, providers can facilitate decisions about the use of NFC parameters (strengths of processing) via sound quality preference judgments using paired comparisons. American Academy of Audiology.

Gender-related needs and preferences in cancer care indicate the need for an individualized approach to cancer patients.

PubMed

Wessels, Hester; de Graeff, Alexander; Wynia, Klaske; de Heus, Miriam; Kruitwagen, Cas L J J; Woltjer, Gerda T G J; Teunissen, Saskia C C M; Voest, Emile E

2010-01-01

Improving quality of care for cancer patients requires insight into their specific wishes, needs, and preferences concerning cancer care. The aim of this study was to explore the impact of gender on cancer patients' needs and preferences. Data were obtained from 386 questionnaires assessing cancer patients' preferences for health care. Multivariate regression analyses were performed with data obtained from medical oncology patients treated in seven Dutch hospitals, using the scales of the questionnaire as dependent variables. Patients rated safety, expertise, performance, and attitude of physicians and nurses highest on their list of preferences. There were significant differences between male and female patients concerning preferences in health care in 15 of the 21 scales and in two of the eight single items. Without exception, women found the care aspects mentioned in these scales and items more important than men. Multivariate regression analysis showed that, of all the patient- and disease-related factors, gender was the most important independent predictor of patient preferences. Gender impacts cancer patients' needs and preferences and should be taken into account for optimal cancer care. Cancer care might be tailored toward gender, for example, with regard to the means and extent of communication, manner and extent of support, counseling and rehabilitation, consultation length, and physician assignment. The results of this study may guide health care professionals and organizations to develop a gender-specific health care approach to further improve cancer patient-centered care.

Gender-Related Needs and Preferences in Cancer Care Indicate the Need for an Individualized Approach to Cancer Patients

PubMed Central

Wessels, Hester; de Graeff, Alexander; Wynia, Klaske; de Heus, Miriam; Kruitwagen, Cas L.J.J.; Woltjer, Gerda T.G.J.; Teunissen, Saskia C.C.M.

2010-01-01

Aim. Improving quality of care for cancer patients requires insight into their specific wishes, needs, and preferences concerning cancer care. The aim of this study was to explore the impact of gender on cancer patients' needs and preferences. Patients and Methods. Data were obtained from 386 questionnaires assessing cancer patients' preferences for health care. Multivariate regression analyses were performed with data obtained from medical oncology patients treated in seven Dutch hospitals, using the scales of the questionnaire as dependent variables. Results. Patients rated safety, expertise, performance, and attitude of physicians and nurses highest on their list of preferences. There were significant differences between male and female patients concerning preferences in health care in 15 of the 21 scales and in two of the eight single items. Without exception, women found the care aspects mentioned in these scales and items more important than men. Multivariate regression analysis showed that, of all the patient- and disease-related factors, gender was the most important independent predictor of patient preferences. Conclusion. Gender impacts cancer patients' needs and preferences and should be taken into account for optimal cancer care. Cancer care might be tailored toward gender, for example, with regard to the means and extent of communication, manner and extent of support, counseling and rehabilitation, consultation length, and physician assignment. The results of this study may guide health care professionals and organizations to develop a gender-specific health care approach to further improve cancer patient–centered care. PMID:20507890

Improving Fatty Acid Availability for Bio-Hydrocarbon Production in Escherichia coli by Metabolic Engineering

PubMed Central

Lin, Fengming; Chen, Yu; Levine, Robert; Lee, Kilho; Yuan, Yingjin; Lin, Xiaoxia Nina

2013-01-01

Previous studies have demonstrated the feasibility of producing fatty-acid-derived hydrocarbons in Escherichia coli. However, product titers and yields remain low. In this work, we demonstrate new methods for improving fatty acid production by modifying central carbon metabolism and storing fatty acids in triacylglycerol. Based on suggestions from a computational model, we deleted seven genes involved in aerobic respiration, mixed-acid fermentation, and glyoxylate bypass (in the order of cyoA, nuoA, ndh, adhE, dld, pta, and iclR) to modify the central carbon metabolic/regulatory networks. These gene deletions led to increased total fatty acids, which were the highest in the mutants containing five or six gene knockouts. Additionally, when two key enzymes in the fatty acid biosynthesis pathway were over-expressed, we observed further increase in strain △cyoA△adhE△nuoA△ndh△pta△dld, leading to 202 mg/g dry cell weight of total fatty acids, ~250% of that in the wild-type strain. Meanwhile, we successfully introduced a triacylglycerol biosynthesis pathway into E. coli through heterologous expression of wax ester synthase/acyl-coenzyme:diacylglycerol acyltransferase (WS/DGAT) enzymes. The added pathway improved both the amount and fuel quality of the fatty acids. These new metabolic engineering strategies are providing promising directions for future investigation. PMID:24147139