Separation behavior of octadecadienoic acid isomers and identification of cis- and trans-isomers using gas chromatography.

PubMed

Shibamoto, Shigeaki; Gooley, Andrew; Yamamoto, Kouhei

2015-01-01

Using a strongly polar cyanopropyl capillary column we have investigated the gas chromatography (GC) separation behaviors of 24 octadecadienoic acid methyl ester (18:2ME) isomers compared against saturated methyl stearate (18:0ME) and arachidic acid methyl ester (20:0ME), and the dependency on the GC column temperature. The 24 isomers were obtained by performing cis-to trans-isomerization of six regioisomers: five of the 18:2ME isomers were prepared by the partial reduction of methyl α-linolenate and methyl γ-linolenate C18 trienoic acids with different double bond positions, whereas the sixth isomer, 18:2ME (c5, c9), was obtained from a raw constituent fatty acid methyl ester (FAME) sample extracted from Japanese yew seeds. There are no reference standards commercially available for 18:2ME isomers, and in elucidating the elution order of these isomers this study should help the future identification of cis- and trans-type of 18:2ME. We also report the identification method of cis- and trans-type of FAME using equivalent chain lengths and attempt the identification of cis- and trans-type of 18:2ME isomers from partially hydrogenated canola oil.

Quantitative high-performance liquid chromatographic determination of retinoids in human serum using on-line solid-phase extraction and column switching. Determination of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid, 4-oxo-all-trans-retinoicacid and 4-oxo-13-cis-retinoic acid.

PubMed

Gundersen, T E; Lundanes, E; Blomhoff, R

1997-03-28

A fully automated isocratic high-performance liquid chromatographic method for the determination of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, has been developed using on-line solid-phase extraction and a column switching technique allowing clean-up and pre-concentration in a single step. A 500-microliter sample of serum was diluted with 750 microliters of a solution containing 20% acetonitrile and the internal standard 9,10-dimethylanthracene. About 1000 microliters of this mixture was injected on a 20 x 4.6 mm I.D. poly ether ether ketone (PEEK) pre-column with titanium frits packed with Bondapak C18, 37-53 microns, 300 A particles. Proteins and very polar compounds were washed out to waste, from the pre-column, with 0.05% trifluoroacetic acid (TFA)-acetonitrile (8.5:1.5, v/v). More than 200 aliquots of diluted serum could be injected on this pre-column before elevated back-pressure enforces replacement. Components retained on the pre-column were backflushed to the analytical column for separation and detection at 360 nm. Baseline separation was achieved using a single 250 x 4.6 mm I.D. Suplex pKb-100 column and a mobile phase containing 69:10:2:16:3 (v/v) of acetonitrile-methanol-n-butanol-2% ammonium acetate-glacial acetic acid. A total time of analysis of less than 30 min, including sample preparation, was achieved. Recoveries were in the range of 79-86%. The limit of detection was 1-7 ng/ml serum and the precision, in the concentration range 20-1000 ng/ml, was between 1.3 and 4.5% for all five compounds. The method was applied for the analysis of human serum after oral administration of 60 mg Roaccutan. The method is well suited for pharmacological studies, while the endogenous levels of some retinoic acid isomers are below the limit of quantitation.

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

PubMed

Periquet, B; Lambert, W; Garcia, J; Lecomte, G; De Leenheer, A P; Mazieres, B; Thouvenot, J P; Arlet, J

1991-11-09

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

Cooxidation of 13-cis-retinoic acid by prostaglandin H synthase.

PubMed

Samokyszyn, V M; Sloane, B F; Honn, K V; Marnett, L J

1984-10-30

Cooxidative metabolism of 13-cis-retinoic acid (13-CIS) via prostaglandin H synthase was investigated employing ram seminal vesicle microsomes. Oxidation of 13-CIS utilizing H2O2, 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-OOH-18:2), or 1-hydroperoxy-5-phenyl-4-pentene was detected by measurement of O2 incorporation. UV spectroscopy and HPLC of extracted incubation mixtures demonstrated that 13-CIS was metabolized to oxidized derivatives. Similar spectral changes and HPLC profiles were obtained with H2O2, 13-OOH-18:2, or arachidonic acid as substrates. 4-Hydroxy-13-cis-retinoic acid and all trans-retinoic acid were products of cooxidation as well as other polar metabolites. Oxidation was inhibited by the antioxidant butylated hydroxyanisole and the spin trap, nitrosobenzene. These results indicate that 13-cis-retinoic acid is cooxidized by prostaglandin H synthase and suggest a free radical mechanism resembling that of lipid peroxidation.

Conceptual biotransformation of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl-beta-glucuronide in rat whole embryo culture.

PubMed

Creech Kraft, J; Juchau, M R

1992-05-28

In cultured rat conceptuses, intraamniotic microinjections of 2500 ng/mL of 4-oxo-13-cis-retinoic acid, 600 ng/mL 4-oxo-all-trans-retinoic acid or 4000 ng/mL all-trans-retinoyl-beta-glucuronide, produce qualitatively and quantitatively similar patterns of dysmorphogenesis as those reported after the intraamniotic microinjection of 250 ng/mL all-trans-retinoic acid [Lee et al., Teratology 44: 313-323, 1991; Creech Kraft et al., Teratology 45: 259-270, 1992]. In the present study, we utilized HPLC techniques to analyze retinoid levels in cultured rat conceptuses, 1.5 hr after intraamniotic microinjections of 4-oxo-13-cis-retinoic acid (2500 ng/mL), 4-oxo-all-trans-retinoic acid (600 ng/mL) or all-trans-retinoyl-beta-glucuronide (4000 ng/mL). Our findings show that, after the microinjections of 4-oxo-all-trans-retinoic acid or 4-oxo-13-cis-retinoic acid (at these selected concentrations), 4-oxo-all-trans-retinoic acid was predominant in the embryos proper at concentrations of about 200 nM. This was roughly equivalent to the levels of all-trans-retinoic acid assayed after microinjections of all-trans-retinoyl-beta-glucuronide (4000 ng/mL). We conclude from these studies that both 4-oxo-all-trans-retinoic acid and all-trans-retinoic acid behave as ultimate or proximate dysmorphogens.

Comparative teratology and transplacental pharmacokinetics of all-trans-retinoic acid, 13-cis-retinoic acid, and retinyl palmitate following daily administrations in rats.

PubMed

Collins, M D; Tzimas, G; Hummler, H; Bürgin, H; Nau, H

1994-07-01

The retinoids are teratogenic in a wide variety of species. In the rat, 13-cis-retinoic acid and retinyl palmitate are significantly less potent teratogens than all-trans-retinoic acid. This investigation questioned whether differing teratogenic potencies of these moieties can be correlated with the concentrations of these drugs and/or metabolites in the embryonic compartment. Approximately equipotent teratogenic doses of these three retinoids were administered and the pharmacokinetics in maternal plasma and embryo of the most prevalent vitamin A metabolites were measured. The glucuronides of the respective retinoids were the predominant metabolites in the maternal plasma, but were not detected in the embryo. Also, the transport of 13-cis-retinoic acid across the placenta occurred to a much lesser extent than the transport of all-trans-retinoic acid. Administration of either all-trans- or 13-cis-retinoic acid causes a depression in the endogenous retinol concentration. This depression is more pronounced in the maternal plasma than in the embryo. The depression of the retinol level in both plasma and embryo after 13-cis-retinoic acid administration (75 mg/kg/day) was greater than the depression after all-trans-retinoic acid (6 mg/kg/day), corroborating the inferential teratological data that the 13-cis-retinoic acid dose was more embryotoxic than the all-trans-retinoic acid dose. Although the dose of all-trans-retinoic acid was less embryotoxic than that of either 13-cis-retinoic acid or retinyl palmitate, the embryonic exposure to all-trans-retinoic acid was considerably larger, as determined by maximum concentration or area under the concentration-versus-time curve, after administration of all-trans-retinoic acid than after either retinyl palmitate or 13-cis-retinoic acid application. These results suggest that embryonic retinoids other than all-trans-retinoic acid--including the administered substances themselves--are important in the teratogenic process induced

Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid indicates differential cytosolic/nuclear localization.

PubMed

Rühl, R; Plum, C; Elmazar, M M; Nau, H

2001-09-01

Isotretinoin (13-cis-retinoic acid [13CRA], Accutane) is used for the treatment of dermatological diseases. Isotretinoin is, however, teratogenic in animals and humans. The mechanism of action of its teratogenicity is still not clearly identified. It has little or no binding properties to cytosolic retinoid-binding proteins or nuclear retinoid receptors (RAR, RXR). One hypothesis is that the teratogenicity of 2 approximately equipotent teratogenic doses of 13CRA and all-trans-retinoic acids (ATRA) could mainly be correlated to ATRA in the nuclei, where the retinoic acid receptors (RARs) are located. To test this hypothesis, female mice at gestational day 11 were treated with approximately equipotent teratogenic doses of 13-cis-retinoic acid (100 mg/kg orally) or all-trans-retinoic acid (10 mg/kg orally) and sacrificed 1 h and 4 h after administration. Embryos were homogenized and centrifuged into 4 fractions, and the purity of the fractions was tested by quantification of marker constituents for various cell compartments. We analyzed, by RP-HPLC, nuclear, mitochondrial, microsomal, and cytosolic fractions, as well as embryo homogenate and maternal plasma. After treatment with 13-cis-retinoic acid, this substance was mainly located in the nuclear fraction of the embryo (approximately 82%), whereas all-trans-retinoic acid, after ATRA treatment, was mainly located in the cytosolic supernatant (approximately 64%). The binding to cellular retinoid-binding protein (CRABP) may limit the access of ATRA to the nucleus, in contrast to 13CRA, which does not bind to CRABP. The concentration of ATRA in the nuclear fraction was similar after administration of either 13CRA or ATRA. The teratogenic activity of 13-cis-retinoic acid could therefore be explained by its access to the nucleus and its possible conversion to all-trans-retinoic acids, which will interact with the nuclear retinoid receptors.

Low density supercritical fluids precipitation of 9-cis and all trans-β-carotenes enriched particulates from Dunaliella salina.

PubMed

Chen, Jian-Ren; Wu, Jia-Jiuan; Lin, Justin Chun-Te; Wang, Yuan-Chuen; Young, Chiu-Chung; Shieh, Chwen-Jen; Hsu, Shih-Lan; Chang, Cheih-Ming J

2013-07-19

In this study, supercritical anti-solvent (SAS) pulverization coupled with reverse phase elution chromatography was employed to isolate 9-cis and trans-β-carotenes from Dunaliella salina. Total concentration of 9-cis (134.7mg/g) and trans-β-carotene (204.2mg/g) was increased from 338.9mg/g of the ultrasonic extract to 859.7mg/g (338.9 for 9-cis and 520.8 for trans) of the elution fraction. The SAS pulverization of the collected fraction further produced submicron-sized particulates containing 932.1mg/g (355.6 for 9-cis and 576.5 for trans) of total β-carotenes with a recovery of 86.3% (83.9% for cis and 87.8% for trans). Effects of two SAS operational conditions on the purity, recovery of total β-carotenes, mean size and morphology of the precipitates were obtained from an experimentally designed method. Generation of micronized particulates enriched with 9-cis and trans-β-carotenes by low-density SAS was proved to be feasible and environmental benign. Copyright © 2013 Elsevier B.V. All rights reserved.

Structural Elucidation of cis / trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry

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

Zheng, Xueyun; Renslow, Ryan S.; Makola, Mpho M.

Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/transmore » isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.« less

Metabolism of oral 9-cis-retinoic acid in the human. Identification of 9-cis-retinoyl-beta-glucuronide and 9-cis-4-oxo-retinoyl-beta-glucuronide as urinary metabolites.

PubMed

Sass, J O; Masgrau, E; Saurat, J H; Nau, H

1995-09-01

Data from a number of investigators suggest that the 9-cis-isomer of RA1 (9-cis-RA) may be a promising agent in chemoprevention and treatment of certain types of cancer. Therefore, clinical studies on this retinoid have been initiated. However, up to now, no information has been published on the metabolism of 9-cis-RA in the human. Herein, we report the first data on retinoid metabolism after multiple administration of 9-cis-RA (20 mg/day po) to human volunteers. After 2 and 12-13 hr, plasma concentrations of 9-cis-RA and its metabolites 9,13-dicis-RA, 13-cis-RA, and all-trans-RA were low. In contrast, dosing with 13-cis-RA yielded much higher plasma retinoid levels. Effects on plasma retinol concentrations did not become obvious after any drug treatment. Several retinoid metabolites were found in the urine of 9-cis-RA-treated individuals, and 9-cis-RAG, as well as 9-cis-4-oxo-RAG, could be identified. After treatment with 9-cis-RA, high concentrations of the administered drug were found in the feces, along with comparably low concentrations of 13-cis-RA, 9,13-dicis-RA, and all-trans-RA. Our report indicates that 9-cis-RA is either eliminated much more rapidly than 13-cis-RA, or it is poorly absorbed, and presents the characterization of two urinary glucuronides.

Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats.

PubMed

Ferguson, Sherry A; Siitonen, Paul H; Cisneros, F Javier; Gough, Bobby; Young, John F

2006-06-01

Male and female Sprague-Dawley rats were orally gavaged with 13-cis-retinoic acid (7.5 or 15 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg) for 7 consecutive days. Blood was collected out to 8 hr after the last gavage on day 7. HPLC serum concentrations of 13-cis-retinoic acid, all-trans-retinoic acid, and 13-cis-4-oxo-retinoic acid were subjected to model independent pharmacokinetic analyses. Peak serum levels of 563 to 1640 ng/ml were observed for rats treated with 13-cis-retinoic acid at 1.5-2 hr after gavage. Peak serum levels of 183 to 267 ng/ml at 1.5 hr after gavage were observed for all-trans-retinoic acids. The elimination half-life of 13-cis-retinoic acid was about 1.5 hr while the elimination half-life of all-trans-retinoic acid was slightly longer. There were no sex differences for any parameter. Serum levels resulting from the 7.5 mg/kg 13-cis-retinoic acid were similar to those of human Accutane users.

Trans-Fatty Acid-Stimulated Mammary Gland Growth in Ovariectomized Mice is Fatty Acid Type and Isomer Specific.

PubMed

Berryhill, Grace E; Miszewski, Susan G; Trott, Josephine F; Kraft, Jana; Lock, Adam L; Hovey, Russell C

2017-03-01

We previously reported that the trans-18:2 fatty acid trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulates mammary gland development independent of estrogen and its receptor. Given the negative consequences of dietary trans-fatty acids on various aspects of human health, we sought to establish whether other trans-fatty acids could similarly induce ovary-independent mammary gland growth in mice. Prepubertal BALB/cJ mice were ovariectomized at 21 days of age then were fed diets enriched with cis-9, trans-11 CLA (c9,t11-CLA), or mixtures of trans-18:1 fatty acids supplied by partially hydrogenated sunflower, safflower, or linseed oil. The resultant mammary phenotype was evaluated 3 weeks later and compared to the growth response elicited by t10,c12-CLA, or the defined control diet. Whereas partially hydrogenated safflower oil increased mammary gland weight, none of the partially hydrogenated vegetable oils promoted mammary ductal growth. Similarly, the c9,t11-CLA supplemented diet was without effect on mammary development. Taken together, our data emphasize a unique effect of t10,c12-CLA in stimulating estrogen-independent mammary gland growth manifest as increased mammary ductal area and elongation that was not recapitulated by c9,t11-CLA or the partially hydrogenated vegetable oil diets.

Plasma pharmacokinetics and metabolism of 13-cis- and all-trans-retinoic acid in the cynomolgus monkey and the identification of 13-cis- and all-trans-retinoyl-beta-glucuronides. A comparison to one human case study with isotretinoin.

PubMed

Kraft, J C; Slikker, W; Bailey, J R; Roberts, L G; Fischer, B; Wittfoht, W; Nau, H

1991-01-01

In order to compare the disposition and metabolism of 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (all-trans-RA) in the nonpregnant female cynomolgus monkey, the plasma concentrations of the parent compound, the oxidized metabolites 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, and the conjugate metabolites 13-cis-retinoyl-beta-glucuronide (13-cis-RAG) and all trans-retinoyl-beta-glucuronide (all-trans-RAG), were determined on day 1 and day 10 after oral dosing of 2 and 10 mg 13-cis- and all-trans-RA/kg/day. Both 13-cis-RAG and all-trans-RAG have been identified as major plasma metabolites in these studies using thermospray/HPLC/mass-spectrometry of the intact conjugates. AUC comparisons from 0-24 hr after administration indicated that 13-cis-RA treatment resulted in primarily cis metabolites and all-trans-RA treatment resulted in primarily trans metabolites, although low levels of isomerization products were observed. Comparison of the two doses (2 and 10 mg/kg, po) revealed that the AUCs were proportional to the dose administered. Although qualitatively similar, elimination of 13-cis-RA in the monkey was more rapid than in the human, and approximately a 10-fold greater dose of 13-cis-RA was required in the monkey to produce the AUC values comparable to the human. The elimination of all-trans-RA in monkey was faster than that of 13-cis-RA and tended to increase with repeated dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations between conceptal concentrations of all-trans-retinoic acid and dysmorphogenesis after microinjections of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinoyl-beta-glucuronide, or retinol in cultured whole rat embryos.

PubMed

Kraft, J C; Juchau, M R

1992-01-01

Retinol (4,000 ng/ml), all-trans-retinoyl-beta-glucuronide (4,000 ng/ml), and 13-cis-retinoic acid (1,500 ng/ml) each produced dysmorphogenic effects qualitatively similar to those elicited by 250 ng/ml of all-trans-retinoic acid after microinjections of the respective individual retinoids into the amniotic cavities of cultured whole rat embryos. Subsequent HPLC analyses of the cultured whole conceptuses, embryos proper, yolk sacs, and culture media (24 hr after microinjections) indicated that conceptal biotransformation of each of the retinoids had occurred during the culture period. All-trans-retinoic acid was present in the embryos proper at quantitatively similar concentrations (20-100 nM) after microinjections of the selected quantities of each of the microinjected retinoids: retinol, all-trans-retinoyl-beta-glucuronide, 13-cis-retinoic acid, or all-trans-retinoic acid. The results suggested that all-trans-retinoic acid acted as an ultimate dysmorphogen for the retinoids tested with respect to the anomalies monitored in the embryo culture system.

9-cis Retinoic Acid is the ALDH1A1 Product that Stimulates Melanogenesis

PubMed Central

Paterson, Elyse K.; Ho, Hsiang; Kapadia, Rubina; Ganesan, Anand K.

2013-01-01

Aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme that catalyzes the conversion of lipid aldehydes to lipid carboxylic acids, plays pleiotropic roles in UV-radiation resistance, melanogenesis, and stem cell maintenance. In this study, a combination of RNAi and pharmacologic approaches were used to determine which ALDH1A1 substrates and products regulate melanogenesis. Initial studies revealed that neither the UV-induced lipid aldehyde 4-hydroxy-2-nonenal nor the ALDH1A1 product all-trans retinoic acid appreciably induced melanogenesis. In contrast, both the ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, Tyrosinase mRNA, and melanin. ALDH1A1 depletion inhibited the ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalyzing the conversion of 9-cis retinal to 9-cis retinoic acid. The addition of potent ALDH1A inhibitors (cyanamide or Angeli’s salt) suppressed Tyrosinase and MITF mRNA accumulation in vitro and also melanin accumulation in skin equivalents, suggesting that 9-cis retinoids regulate melanogenesis in the intact epidermis. Taken together, these studies not only identify cyanamide as a potential novel treatment for hyperpigmentary disorders, but also identify 9-cis retinoic acid as a pigment stimulatory agent that may have clinical utility in the treatment of hypopigmentary disorders, such as vitiligo. PMID:23489423

The cis-9,trans-11 isomer of conjugated linoleic acid (CLA) lowers plasma triglyceride and raises HDL cholesterol concentrations but does not suppress aortic atherosclerosis in diabetic apoE-deficient mice.

PubMed

Nestel, Paul; Fujii, Akihiko; Allen, Terri

2006-12-01

Reduction in atherosclerosis has been reported in experimental animals fed mixtures of conjugated linoleic acid (CLA). In this study, the major naturally occurring CLA isomer (cis-9,trans-11) was tested in an atherosclerosis-prone mouse model. In a model of insulin deficient apoE deficient mice, 16 animals were fed for 20 weeks with supplemental CLA (09.%, w/w) and compared with a similar number of mice of this phenotype. A control comparison was made of metabolic changes in non-diabetic apoE deficient mice that develop little atherosclerosis over 20 weeks. At 20 weeks, plasma lipids were measured and aortic atherosclerosis quantified by Sudan staining in the arch, thoracic and abdominal segments. The diabetic apoE deficient mice developed marked dyslipidemia, primarily as cholesterol-enriched chylomicron and VLDL-sized lipoproteins and atherosclerosis in the aortic arch. However, there were no significant differences between CLA fed and non-CLA fed mice in either phenotype in plasma cholesterol concentration (in diabetic: 29.4+/-7.7 and 29.5+/-5.9 mmol/L, respectively) or in the area of aortic arch atherosclerosis (in diabetic: 24.8+/-10.3 and 27.6+/-7.7%, respectively). However, among diabetic mice the triglyceride concentration in triglyceride-rich lipoproteins was significantly lower in those fed CLA (for plasma 2.2+/-0.8 to 1.1+/-0.3 mmol/L; P<0.001), a significant difference that was seen also in the non-diabetic mice in which HDL cholesterol increased significantly with CLA (0.35+/-0.12-0.56+/-0.15 mmol/L). In this atherosclerosis-prone model, the diabetic apoE deficient mouse, supplemental 0.9% CLA (cis-9,trans-11) failed to reduce the severity of aortic atherosclerosis, although plasma triglyceride concentration was substantially lowered and HDL cholesterol raised.

1H NMR Measurement of the Trans Cis Photoisomerization of Cinnamic Acid Derivatives

NASA Astrophysics Data System (ADS)

Danylec, Basil; Iskander, Magdy N.

2002-08-01

1H NMR spectroscopy was used to follow the course of the photochemical conversion of methyl p-hydroxy-trans-cinnamate to the thermodynamically less stable cis isomer. Integration of the new olefinic cis proton doublet (5.66 ppm, J = 12.9 Hz), which was then compared to the trans isomer (6.15 ppm, J = 15.9 Hz), allowed the determination of the relative amounts of these two isomers.

In vitro and in vivo metabolism of all-trans- and 13-cis-retinoic acid in hamsters. Identification of 13-cis-4-oxoretinoic acid.

PubMed

Frolik, C A; Roller, P P; Roberts, A B; Sporn, M B

1980-09-10

Administration of either all-trans-[3H]- or 13-cis-[3H]retinoic acid to hamsters fed a normal diet results in the formation of a number of polar metabolites. At least one of these metabolites has been shown to be common to both isomers of retinoic acid and can be generated in a hamster liver 10,000 X g supernatant system using 13-cis-retinoic acid as substrate. It has been identified as 13-cis-4-oxoretinoic acid by mass spectral, ultraviolet absorption, and proton NMR characteristics, as well as by its co-migration with synthetic 13-cis-4-oxoretinoic acid in two different high pressure liquid chromatographic systems. In addition, its metabolic precursor, 13-cis-4-hydroxyretinoic acid, has been tentatively identified. These compounds are believed to be early metabolites in the elimination pathway of retinoic acid from the body.

Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo.

PubMed

Aliwarga, Theresa; Raccor, Brianne S; Lemaitre, Rozenn N; Sotoodehnia, Nona; Gharib, Sina A; Xu, Libin; Totah, Rheem A

2017-11-01

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling properties. AA is an ω-6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds. In plasma and red blood cell (RBC) membranes, cis- and trans-EETs have been observed, and both have multiple physiological functions. We developed a sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay that separates cis- and trans- isomers of EETs and applied it to determine the relative distribution of cis- vs. trans-EETs in reaction mixtures of AA subjected to free radical oxidation in benzene and liposomes in vitro. We also determined the in vivo distribution of EETs in several tissues, including human and mouse heart, and RBC membranes. We then measured EET levels in heart and RBC of young mice compared to old. Formation of EETs in free radical reactions of AA in benzene and in liposomes exhibited time- and AA concentration-dependent increase and trans-EET levels were higher than cis-EETs under both conditions. In contrast, cis-EET levels were overall higher in biological samples. In general, trans-EETs increased with mouse age more than cis-EETs. We propose a mechanism for the non-enzymatic formation of cis- and trans-EETs involving addition of the peroxyl radical to one of AA's double bonds followed by bond rotation and intramolecular homolytic substitution (S H i). Enzymatic formation of cis-EETs by cytochrome P450 most likely occurs via a one-step concerted mechanism that does not allow bond rotation. The ability to accurately measure

Developmental stage-associated differences in the transplacental distribution of 13-cis- and all-trans-retinoic acid as well as their glucuronides in rats and mice.

PubMed

Tzimas, G; Collins, M D; Nau, H

1995-07-01

In mice and rats, 13-cis-retinoic acid (13-cis-RA) has a much lower teratogenic potency than all-trans-retinoic acid (all-trans-RA). Previous studies on Gestational Day (GD) 11 or 12 (in mice or rats, respectively) showed a limited transfer of 13-cis-RA to the embryo, in contrast to the efficient transplacental passage of all-trans-RA. In the present study we examined if the distribution between maternal circulation and embryo of 13-cis- and all-trans-RA as well as their metabolites is different at gestational times when the placenta is developing from a choriovitelline to a chorioallantoic type. In the first experiment, 13-cis-RA was administered orally to pregnant rats (75 mg/kg/day) daily, from either GD 7 to 12 or 11 to 16. In the second experiment, 13-cis-RA or all-trans-RA was given orally to pregnant mice once on either GD 11 or 14, at two dose levels (10 and 100 mg/kg). HPLC analysis of plasma and embryo samples collected at various time points post-treatment showed that 13-cis-RA was predominantly metabolized to its beta-glucuronide (13-cis-RAG) while all-trans-RA was primarily biotransformed to all-trans-4-oxo-RA and to a lesser extent to all-trans-RAG. 13-cis-RA showed a more efficient transplacental passage to the rat embryo on GD 16 than on GD 12, as indicated by higher ratios of embryonic to maternal plasma concentrations (E/M concentration ratio) on GD 16 vs. GD 12 and its E/M ratio of area-under-the-concentration-time-curve values (E/M AUC ratio; twofold higher on GD 16 vs. GD 12). In the mouse, the E/M concentration ratio of 13-cis-RA was significantly higher on GD 14 than on GD 11 only at the low dose. On the other hand, all-trans-RA and all-trans-4-oxo-RA showed an efficient transfer to the mouse embryo at both gestational times. In both species, 13-cis- and all-trans-RAG embryonic concentrations on the later gestational days exceeded significantly the corresponding ones on the earlier gestational days which resulted in far higher E

A sensitive high-pressure liquid chromatography/particle beam/mass spectrometry assay for the determination of all-trans-retinoic acid and 13-cis-retinoic acid in human plasma.

PubMed

Lehman, P A; Franz, T J

1996-03-01

A highly sensitive assay for the measurement of all-trans-retinoic acid (tretinoin) and 13-cis-retinoic acid (isotretinoin) has been developed. Collected plasma samples were protein precipitated with 2-propanol followed by solid phase extraction. The retinoic acids were subsequently derivatized to their pentafluorobenzyl esters followed by separation and isolation by reverse phase high-pressure liquid chromatography. The HPLC eluate was directed to a mass spectrometer via a particle beam interface. Selected ion monitoring (299 m/z) for the retinoic acid's carboxylate anion produced by negative chemical ionization using methane reagent gas achieved minimum detection limits of 25 pg injected. Endogenous blood levels in 19 male and 9 female subjects were measured. It was found that females have significantly more all-trans-retinoic acid than males and that both sexes demonstrate significantly more all-trans-retinoic acid then 13-cis-retinoic acid.

The high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid (isotretinoin) is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not of isomerization to all-trans-retinoic acid.

PubMed

Tzimas, G; Bürgin, H; Collins, M D; Hummler, H; Nau, H

1994-01-01

Previous studies suggested that the rabbit is much more susceptible to the teratogenic action of 13-cis-retinoic acid (13-cis-RA) than the mouse or the rat, while the teratogenicity of all-trans-RA was comparable in these species. In the present study we investigated if pharmacokinetics can explain these species- and structure-related differences. The embryotoxic and teratogenic potential of all-trans-retinoic acid (all-trans-RA) and 13-cis-RA were evaluated in the Swiss hare rabbit after oral administration of daily doses of the two drugs throughout organogenesis, from gestation day (GD) 6 to 18 (plug day = GD 0). All-trans-RA was given at dose levels of 0.7, 2 or 6 mg/kg body weight per day and 13-cis-RA at 3, 7.5 or 10 mg/kg per day. The doses needed to elicit a minimum teratogenic response were found to be 6 mg/kg per day for all-trans-RA and 10 mg/kg per day for 13-cis-RA. Using these doses, transplacental pharmacokinetics of all-trans- and 13-cis-RA were performed. Pregnant rabbits were treated once daily from GD 7 to 12 and plasma and embryo samples were collected for HPLC analysis at various time intervals after the final dose. The main plasma metabolites of all-trans- and 13-cis-RA were all-trans-beta-glucuronide (all-trans-RAG) and 13-cis-4-oxo-RA, respectively. The elimination of 13-cis-RA and its metabolites from maternal plasma were much slower than of all-trans-RA resulting in accumulation of the 13-cis-isomers in plasma. Marked differences in the placental transfer of the two drugs and their metabolites were observed. All-trans-RA and all-trans-4-oxo-RA were efficiently transferred to the rabbit embryo, reaching concentrations similar to the plasma levels. On the contrary, the 13-cis-isomers reached the embryo to a lesser extent. Despite its limited placental transfer, a considerable embryonic exposure to 13-cis-RA and 13-cis-4-oxo-RA was noticed after treatment with isotretinoin, as indicated by their area-under-the-concentration-time-curve (AUC

Identification of activities that catalyze the cis-trans isomerization of the double bond of a mono-unsaturated fatty acid in Pseudomonas sp. strain E-3.

PubMed

Okuyama, H; Enari, D; Shibahara, A; Yamamoto, K; Morita, N

1996-06-01

A cell-free extract of Pseudomonas sp. strain E-3 catalyzed the conversion of 9-cis-hexadecenoic acid [16:1(9c)] to 9-trans-hexadecenoic acid [16:1(9t)] in the free acid form and when 16:1(9c) was esterified to phosphatidylethanolamine (PE). The cytosolic fraction catalyzed the isomerizations of free 16:1(9c) by itself and of 16:1(9c) esterified to PE in the presence of the membrane fraction. Tracer experiments using [2,2-2H2]16:1(9c) demonstrated that the isomerization of free 16:1(9c) occurred independently of the isomerization of 16:1(9c) esterified to PE, indicating that this bacterium has two types of activities that catalyze the cis-trans isomerization of the double bond of a mono-unsaturated fatty acid.

Prediction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information.

PubMed

Song, Jiangning; Burrage, Kevin; Yuan, Zheng; Huber, Thomas

2006-03-09

The majority of peptide bonds in proteins are found to occur in the trans conformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt the cis form. Proline cis/trans isomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of proline cis/trans isomerization in proteins would have many important applications towards the understanding of protein structure and function. In this paper, we propose a new approach to predict the proline cis/trans isomerization in proteins using support vector machine (SVM). The preliminary results indicated that using Radial Basis Function (RBF) kernels could lead to better prediction performance than that of polynomial and linear kernel functions. We used single sequence information of different local window sizes, amino acid compositions of different local sequences, multiple sequence alignment obtained from PSI-BLAST and the secondary structure information predicted by PSIPRED. We explored these different sequence encoding schemes in order to investigate their effects on the prediction performance. The training and testing of this approach was performed on a newly enlarged dataset of 2424 non-homologous proteins determined by X-Ray diffraction method using 5-fold cross-validation. Selecting the window size 11 provided the best performance for determining the proline cis/trans isomerization based on the single amino acid sequence. It was found that using multiple sequence alignments in the form of PSI-BLAST profiles could significantly improve the prediction performance, the prediction accuracy increased from 62.8% with single sequence to 69.8% and Matthews Correlation Coefficient (MCC) improved from 0.26 with single local sequence to 0.40. Furthermore, if coupled with the predicted secondary structure information by PSIPRED, our method yielded a prediction accuracy of 71.5% and MCC of 0.43, 9% and 0

Trans-cis molecular photoswitching in interstellar space

NASA Astrophysics Data System (ADS)

Cuadrado, S.; Goicoechea, J. R.; Roncero, O.; Aguado, A.; Tercero, B.; Cernicharo, J.

2016-11-01

As many organic molecules, formic acid (HCOOH) has two conformers (trans and cis). The energy barrier to internal conversion from trans to cis is much higher than the thermal energy available in molecular clouds. Thus, only the most stable conformer (trans) is expected to exist in detectable amounts. We report the first interstellar detection of cis-HCOOH. Its presence in ultraviolet (UV) irradiated gas exclusively (the Orion Bar photodissociation region), with a low trans-to-cis abundance ratio of 2.8 ± 1.0, supports a photoswitching mechanism: a given conformer absorbs a stellar photon that radiatively excites the molecule to electronic states above the interconversion barrier. Subsequent fluorescent decay leaves the molecule in a different conformer form. This mechanism, which we specifically study with ab initio quantum calculations, was not considered in Space before but likely induces structural changes of a variety of interstellar molecules submitted to UV radiation. This paper makes use of observations obtained with the IRAM-30 m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).

Teratogenicity and transplacental pharmacokinetics of 13-cis-retinoic acid in rabbits.

PubMed

Eckhoff, C; Chari, S; Kromka, M; Staudner, H; Juhasz, L; Rudiger, H; Agnish, N

1994-03-01

No embryotoxic or teratogenic effects, considered to be treatment related, were observed in rabbits after daily oral doses of 3 mg/kg of 13-cis-retinoic acid (13-cis-RA) from Day 8 to Day 11 of gestation. In contrast, treatment with 15 mg/kg/day significantly increased the rate of fetal resorptions (22%) and 13 out of 68 surviving fetuses (16%) were malformed. Pharmacokinetic studies with both dosing regimens of 13-cis-RA in pregnant rabbits showed that on Day 11 of gestation, high concentrations of parent compound, 13-cis-RA, and its major metabolite, 13-cis-4-oxoRA, existed in maternal plasma. Much lower concentrations were found for all-trans-4-oxoRA and all-trans-RA. The area under the concentration-time curve (AUC) of all-trans-RA following the 15 mg/kg/day dosing regimen of 13-cis-RA was only 1.2% that of parent compound 13-cis-RA. At this dose, embryo levels of 13-cis-RA, 13-cis-4-oxoRA, and all-trans-4-oxoRA were 2.5-, 4.7-, and 3.6-fold higher by AUC comparison (24-hr period of Day 11) compared with the dose of 3 mg/kg. However, embryo levels of all-trans-RA were virtually identical at both doses and were, in fact, somewhat lower than endogenous concentrations measured in untreated rabbit embryos. In contrast to mice, where isomerization from 13-cis- to all-trans-RA was suggested to be crucial for the teratogenic action of 13-cis-RA, we found that the teratogenic action of 13-cis-RA (15 mg/kg/day) in rabbits is characterized by increased whole embryo concentrations of 13-cis-RA, 13-cis-4-oxoRA, and all-trans-4-oxoRA, but not of all-trans-RA.

Determination of 13-cis-retinoic acid and its major metabolite, 4-oxo-13-cis-retinoic acid, in human blood by reversed-phase high-performance liquid chromatography.

PubMed

Vane, F M; Stoltenborg, J K; Buggé, C J

1982-02-12

A high-performance liquid chromatography (HPLC) method for the quantitation of 13-cis-retinoic acid (13-cis-RA) and its major metabolite, 4-oxo-13-cis-RA, in human blood has been developed. The method includes extraction of 1 ml of blood with diethyl ether at pH 6 and the analysis of the extract by reversed-phase HPLC with solvent programming and detection at 365 nm. The quantitation ranges for 13-cis-RA and 4-oxo-13-cis-RA are 10--2000 and 50--2000 ng/ml of blood, respectively. The method also provides estimates of the concentrations of all-trans-RA and 4-oxo-all-trans-RA. The mean intra- and inter-assay variabilities for all four compounds were 6% or less. The method separates 13-cis-RA and 4-oxo-13-cis-RA from 9-cis-RA, all-trans-RA, 4-oxo-all-trans-RA, and some other possible metabolites, such as hydroxy and epoxy retinoic acids. The method has been successfully applied to the analyses of over 1200 blood samples from four 13-cis-RA clinical studies.

ATR-FTIR spectroscopic investigation of the cis- and trans-bis-(α-amino acids) copper(II) complexes

NASA Astrophysics Data System (ADS)

Berestova, Tatyana V.; Kuzina, Lyudmila G.; Amineva, Natalya A.; Faizrakhmanov, Ilshat S.; Massalimov, Ismail A.; Mustafin, Akhat G.

2017-06-01

The crystalline phases of the trans-(a) and cis-(b)-isomers of bis-(α-amino acids) copper(II) complexes [Cu(bL)2] 1-5 (bL - bidentate ligand: gly (1), S-ala (2), R,S-val (3), (±)-thr (4), R,S-phe (5)) were studied by ATR-FTIR spectroscopy in the mid region IR spectrum. It was established that asymmetric νas(COO) and symmetric νs(COO) stretching vibrations of carboxylic groups of 1-5 are sensitive to change of the geometric structure and have a different maxima for the trans(a)- and cis(b)-isomers. It found that νas(COO) and νs(COO) stretching vibrations of cis-isomers are broadened and shifted to longer wavelengths (b) as compared with trans-isomers (a). Shown that peculiarities of crystal packing molecules of geometric isomers may affect on carboxylate stretching vibration bis-α-amino acids complexes copper(II) 1-5 a,b.

Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity.

PubMed Central

Heipieper, H J; Diefenbach, R; Keweloh, H

1992-01-01

A trans unsaturated fatty acid was found as a major constituent in the lipids of Pseudomonas putida P8. The fatty acid was identified as 9-trans-hexadecenoic acid by gas chromatography, argentation thin-layer chromatography, and infrared absorption spectrometry. Growing cells of P. putida P8 reacted to the presence of sublethal concentrations of phenol in the medium with changes in the fatty acid composition of the lipids, thereby increasing the degree of saturation. At phenol concentrations which completely inhibited the growth of P. putida, the cells were still able to increase the content of the trans unsaturated fatty acid and simultaneously to decrease the proportion of the corresponding 9-cis-hexadecenoic acid. This conversion of fatty acids was also induced by 4-chlorophenol in nongrowing cells in which the de novo synthesis of lipids had stopped, as shown by incorporation experiments with labeled acetate. The isomerization of the double bond in the presence of chloramphenicol indicates a constitutively operating enzyme system. The cis-to-trans modification of the fatty acids studied here apparently is a new way of adapting the membrane fluidity to the presence of phenols, thereby compensating for the elevation of membrane permeability induced by these toxic substances. PMID:1622260

[13C]-Specific labeling of 8-2' linked (-)-cis-blechnic, (-)-trans-blechnic and (-)-brainic acids in the fern Blechnum spicant

NASA Technical Reports Server (NTRS)

Davin, Laurence B.; Wang, Chang-Zeng; Helms, Gregory L.; Lewis, Norman G.

2003-01-01

In vivo administration experiments using stable (13C) and radio (14C) labeled precursors established that the optically active 8-2' linked lignans, (-)-cis-blechnic, (-)-trans-blechnic and (-)-trans-brainic acids, were directly derived from L-phenylalanine, cinnamate, and p-coumarate but not either from tyrosine or acetate. The radiochemical time course data suggest that the initial coupling product is (-)-cis-blechnic acid, which is then apparently converted into both (-)-trans-blechnic and (-)-trans-brainic acids in vivo. These findings provide additional evidence for vascular plant proteins engendering distinct but specific phenolic radical-radical coupling modes, i.e., for full control over phenylpropanoid coupling in vivo, whether stereoselective or regiospecific.

Recombinant human glutathione S-transferases catalyse enzymic isomerization of 13-cis-retinoic acid to all-trans-retinoic acid in vitro.

PubMed Central

Chen, H; Juchau, M R

1998-01-01

The steric conversion of 13-cis-retinoic acid (13-cRA) to all-trans-retinoic acid (t-RA) has been proposed as an activation mechanism for the observed therapeutic and teratogenic activities of 13-cRA. Here we have investigated the catalysis of isomerization of 13-cRA to t-RA by recombinant human glutathione S-transferases (GSTs). Substrate was incubated with GST in 0.1 M sodium phosphate buffer, pH 7.5, at 37 degrees C in total darkness. The t-RA generated was measured quantitatively by HPLC. Under the reaction conditions used, GSTP1-1 was far more effective than human GSTM1-1 or human GSTA1-1 in catalysing the isomerization reaction. The reaction catalysed by GSTP1-1 showed substrate saturation and the Km and Vmax values for the reaction were approx. 7 microM and 650 pmol/min per nmol respectively. The reaction rate increased linearly with increasing enzyme concentration. The reaction was inhibited both by heat treatment and by S-decylglutathione (a potent inhibitor of transferase activity associated with GST). Additions of polyclonal rabbit antiserum for human GSTP1-1 to the reaction resulted in a significant decrease in generation of t-RA (70-80%). In addition, ethacrynic acid, a selective substrate for Pi isoforms of GST, also inhibited the isomerization of 13-cRA to t-RA catalysed by GSTP1-1. Under the same reaction conditions, GSTP1-1 was much less effective in catalysing the steric conversion of 9-cis-retinoic acid to t-RA, indicating that the enzyme was stereospecific for the conversion of 13-cRA to t-RA. These observations suggest that enzymic catalysis was the primary mechanism for the GSTP1-1-dependent conversion of 13-cRA to t-RA. Reactions catalysed by a purified rat hepatic GST Pi isoenzyme proceeded more slowly than reactions catalysed by human GSTP1-1. Comparative studies also showed that there were marked species differences in catalytic activities between various purified mammalian hepatic GST mixtures. PMID:9806904

Recombinant human glutathione S-transferases catalyse enzymic isomerization of 13-cis-retinoic acid to all-trans-retinoic acid in vitro.

PubMed

Chen, H; Juchau, M R

1998-11-15

The steric conversion of 13-cis-retinoic acid (13-cRA) to all-trans-retinoic acid (t-RA) has been proposed as an activation mechanism for the observed therapeutic and teratogenic activities of 13-cRA. Here we have investigated the catalysis of isomerization of 13-cRA to t-RA by recombinant human glutathione S-transferases (GSTs). Substrate was incubated with GST in 0.1 M sodium phosphate buffer, pH 7.5, at 37 degrees C in total darkness. The t-RA generated was measured quantitatively by HPLC. Under the reaction conditions used, GSTP1-1 was far more effective than human GSTM1-1 or human GSTA1-1 in catalysing the isomerization reaction. The reaction catalysed by GSTP1-1 showed substrate saturation and the Km and Vmax values for the reaction were approx. 7 microM and 650 pmol/min per nmol respectively. The reaction rate increased linearly with increasing enzyme concentration. The reaction was inhibited both by heat treatment and by S-decylglutathione (a potent inhibitor of transferase activity associated with GST). Additions of polyclonal rabbit antiserum for human GSTP1-1 to the reaction resulted in a significant decrease in generation of t-RA (70-80%). In addition, ethacrynic acid, a selective substrate for Pi isoforms of GST, also inhibited the isomerization of 13-cRA to t-RA catalysed by GSTP1-1. Under the same reaction conditions, GSTP1-1 was much less effective in catalysing the steric conversion of 9-cis-retinoic acid to t-RA, indicating that the enzyme was stereospecific for the conversion of 13-cRA to t-RA. These observations suggest that enzymic catalysis was the primary mechanism for the GSTP1-1-dependent conversion of 13-cRA to t-RA. Reactions catalysed by a purified rat hepatic GST Pi isoenzyme proceeded more slowly than reactions catalysed by human GSTP1-1. Comparative studies also showed that there were marked species differences in catalytic activities between various purified mammalian hepatic GST mixtures.

Simultaneous analysis of retinol, all-trans- and 13-cis-retinoic acid and 13-cis-4-oxoretinoic acid in plasma by liquid chromatography using on-column concentration after single-phase fluid extraction.

PubMed

Teerlink, T; Copper, M P; Klaassen, I; Braakhuis, B J

1997-06-20

A reversed-phase high-performance liquid chromatographic method for the simultaneous analysis of retinol, all-trans-retinoic acid, 13-cis-retinoic acid and 13-cis-4-oxoretinoic acid in human plasma and cell culture medium is described. Sample preparation involves precipitation of proteins and extraction of retinoids with 60% acetonitrile. After centrifugation, the acetonitrile content of the supernatant is reduced to 45%, allowing on-column concentration of analytes. Injection volumes up to 2.0 ml (equivalent to 0.525 ml of sample) can be used without compromising chromatographic resolution of all-trans-retinoic acid and 13-cis-retinoic acid. Retinoids were stable in this extract and showed no isomerization when stored in the dark in a cooled autosampler, allowing automated analysis of large series of samples. Recoveries from spiked plasma samples were between 95 and 103%. Although no internal standard was used, the inter-assay precision for all retinoids was better than 6% and 4% at concentrations of 30 nM and 100 nM, respectively. The method is a valuable tool for the study of cellular metabolism of all-trans-retinoic acid, as polar metabolites of this compound can be detected with high sensitivity in cell culture media.

Solid-state stability studies of 13-cis-retinoic acid and all-trans-retinoic acid using microcalorimetry and HPLC analysis.

PubMed

Tan, X; Meltzer, N; Lindebaum, S

1992-09-01

The solid-state stabilities of 13-cis-retinoic acid and all-trans-retinoic acid in the presence and absence of oxygen were investigated. The samples were first evaluated using microcalorimetry. The rate laws of different samples under different conditions were deduced from the shapes of the heat flow curves, and the activation energies of the reactions were determined from Arrhenius plots. Under an air atmosphere, the decomposition of 13-cis-retinoic acid is an autocatalytic reaction, while all-trans-retinoic acid undergoes a zero-order process. The degradation of the two compounds at a selected elevated temperature was also determined utilizing HPLC analysis. This technique confirmed the decomposition kinetics. Hence, their half-lives and shelf lives at room temperature could be calculated. Under a nitrogen atmosphere, the microcalorimetric experiment showed a first-order phenomenon for both samples, but HPLC analysis showed no degradation, suggesting that the two samples, in the absence of oxygen, undergo only a physical change.

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides.

PubMed

Gómez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, José

2007-11-09

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.

Regioselective cis-trans isomerization of arachidonic double bonds by thiyl radicals: the influence of phospholipid supramolecular organization.

PubMed

Ferreri, Carla; Samadi, Abdelouahid; Sassatelli, Fabio; Landi, Laura; Chatgilialoglu, Chryssostomos

2004-02-04

Trans unsaturated fatty acids in humans may be originated by two different contributions. The exogenous track is due to dietary supplementation of trans fats and the endogenous path deals with free-radical-catalyzed cis-trans isomerization of fatty acids. Arachidonic acid residue (5c,8c,11c,14c-20:4), which has only two out of the four double bonds deriving from the diet, was used to differentiate the two paths and to assess the importance of a radical reaction. A detailed study on the formation of trans phospholipids catalyzed by the HOCH2CH2S* radical was carried out on L-alpha-phosphatidylcholine from egg lecithin and 1-stearoyl-2-arachidonoyl-L-alpha-phosphatidylcholine (SAPC) in homogeneous solution or in large unilamellar vesicles (LUVET). Thiyl radicals were generated from the corresponding thiol by either gamma-irradiation or UV photolysis, and the reaction course was followed by GC, Ag/TLC, and 13C NMR analyses. The isomerization was found to be independent of cis double bond location (random process) in i-PrOH solution. In the case of vesicles, the supramolecular organization of lipids produced a dramatic change of the isomerization outcome: (i) in egg lecithin, the reactivity of arachidonate moieties is higher than that of oleate and linoleate residues, (ii) in the linoleate residues of egg lecithin, the 9t,12c-18:2 isomer prevailed on the 9c,12t-18:2 isomer (3:1 ratio), and (iii) a regioselective isomerization of SAPC arachidonate residues occurred in the 5 and 8 positions. This effect of "positional preference" indicates that thiyl radicals entering the hydrophobic region of the membrane bilayer start to isomerize polyunsaturated fatty acid residues having the double bonds nearest to the membrane surfaces. We propose that arachidonic acid and its trans isomers can function as biomarkers in membranes for distinguishing the two trans fatty acid-forming pathways.

Structural analysis of conjugated linoleic acid produced by Lactobacillus plantarum, and factors affecting isomer production.

PubMed

Kishino, Shigenobu; Ogawa, Jun; Ando, Akinori; Iwashita, Takashi; Fujita, Tsuyoshi; Kawashima, Hiroshi; Shimizu, Sakayu

2003-01-01

An isomer of the conjugated linoleic acid (CLA) produced from linoleic acid by Lactobacillus plantarum was identified as cis-9,trans-11-octadecadienoic acid by proton nuclear magnetic resonance spectroscopy. Together with earlier results, we concluded that the bacterium produces two CLA isomers, cis-9,trans-11- and trans-9,trans-11-octadecadienoic acid from linoleic acid. The addition of L-serine, glucose, AgNO3, or NaCl to the reaction mixture reduced production of the latter.

Synthesis of cis-4-trifluoromethyl- and cis-4-difluoromethyl-l-pyroglutamic acids.

PubMed

Qiu, Xiao-Long; Qing, Feng-Ling

2003-05-02

Efforts to synthesize 4-trifluoromethyl- and 4-difluoromethyl-l-pyroglutamic acids are described. After many arduous efforts, we successfully synthesized our target molecules cis-4-trifluoromethyl-l-pyroglutamic acid 25 and cis-4-difluoromethyl-l-pyroglutamic acid 26 from trans-4-hydroxy-l-proline through oxidation of fluorinated prolinates with RuO(4).

Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.

PubMed

Ferguson, Sherry A; Cisneros, F Javier; Gough, B; Hanig, Joseph P; Berry, Kimberly J

2005-10-01

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid.

PubMed

Cisneros, F J; Gough, B J; Patton, R E; Ferguson, S A

2005-01-01

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints. Copyright (c) 2005 John Wiley & Sons, Ltd.

Prostaglandin H synthase-catalyzed oxidation of all-trans- and 13-cis-retinoic acid to carbon-centered and peroxyl radical intermediates.

PubMed

Freyaldenhoven, M A; Lloyd, R V; Samokyszyn, V M

1996-06-01

Due to the importance of all-trans-retinoic acid (RA) in the treatment of various dermatological conditions and the wide distribution of prostaglandin H synthase (PGHS) in tissues, we have further examined the mechanisms involved in the hydroperoxide-dependent cooxidation of RA and its isomer, 13-cis-retinoic acid ((13Z)-RA), by PGHS. Hydroperoxide-dependent, PGHS-catalyzed oxidation of RA and (13Z)-RA was shown to form free radical adducts, using electron spin resonance (ESR) spin trapping techniques and 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) or 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-OOH-18:2) as hydroperoxide substrates. Utilization of the spin trap alpha-phenyl-N-tert-butylnitrone (PBN) resulted in the detection of (13Z)-RA-PBN and RA-PBN adducts whose spectra were characterized by hyperfine coupling constants of aH = 4.16/aN = 15.69 and aH = 3.01/aN =15.92, respectively. Identical experiments under anaerobic conditions were carried out using the spin trap 2-methyl-2-nitrosopropane (NtB) which yielded nitroxide adducts whose spectra were characterized by a triplet of doublets with values of aH = 3.49/aN = 15.84 for the (13Z)-RA adduct and aH = 3.49/aN = 15.88 for the RA adduct. These results are indicative of secondary carbon-centered radical formation. We also used (+)-benzo[a]pyrene 7(S),8(S)-dihydrodiol ((+)-BP-7,8-diol) as a peroxyl radical probe. The results demonstrated the formation of (+)-BP-7,8-diol-derived tetrols, with the trans-anti tetrol representing the major oxidation product in systems undergoing PPHP-dependent, PGHS-catalyzed oxidation of (13Z)-RA or RA. These results are consistent with the formation of peroxyl radicals in these systems. In all experiments, the (13Z)-RA isomer appeared to be a better substrate for the enzyme compared to the all-trans isomer. Collectively these results provide further evidence to support the previously proposed mechanism for retinoid oxidation by PGHS involving the intermediacy of C4 carbon

All-trans-retinoic acid and 13-cis-retinoic acid: pharmacokinetics and biological activity in different cell culture models of human keratinocytes.

PubMed

Schroeder, M; Zouboulis, C C

2007-02-01

Despite its known biological effect on epithelial cells, 13- CIS-retinoic acid shows low binding affinity to either cellular retinoic acid-binding proteins or nuclear retinoid receptors compared to its isomer all- TRANS-retinoic acid. We have postulated a prodrug-drug relation with 13- CIS-retinoic acid which isomerizes to all- TRANS-retinoic acid. On the other hand, the biological effects of these two compounds can differ in the widely used cell culture models of HaCaT and normal primary keratinocytes. In this study, we seeded HaCaT and normal keratinocytes at high densities leading to early confluence in order to imitate high keratinocyte proliferation, such as in acne and psoriasis, while to model decreased keratinocyte proliferation, as in aged and steroid-damaged skin, cells were seeded at a low density. High performance liquid chromatography was administered to examine retinoid uptake and metabolism in monolayer HaCaT and normal keratinocyte cultures and the 4-methylumbelliferyl heptanoate assay to estimate cell growth at different cell densities. Major qualitative and quantitative differences were detected in the two cell types regarding intracellular 13- CIS-retinoic acid isomerization to all- TRANS-retinoic acid. On the other hand, the two retinoic acid isomers showed similar effects on cell growth of both cell types tested with increasing proliferation at low cell densities, but being rather inactive at high ones in normal keratinocytes and exhibiting an antiproliferative effect in HaCaT keratinocytes. The missing effect of retinoids on cell proliferation in high seeding densities of normal keratinocytes may indicate that the normalizing activity of retinoids on hyperkeratotic diseases, such as acne or psoriasis, is likely to be carried out by modulation of cell differentiation than cell growth. On the other hand, induced keratinocyte proliferation in low seeding densities may provide an explanation for the acanthosis induced by topical retinoids in aged

Separation of Cis-Trans Phospholipid Isomers using Reversed Phase LC with High Resolution MS Detection

PubMed Central

Bird, Susan S.; Marur, Vasant R.; Stavrovskaya, Irina G.; Kristal, Bruce S.

2012-01-01

The increased presence of synthetic trans fatty acids into western diets has been shown to have deleterious effects on physiology and raising an individual’s risk of developing metabolic disease, cardiovascular disease, and stroke. The importance of these fatty acids for health and the diversity of their (patho) physiological effects suggest that not only should the free trans fatty acids be studied, but that monitoring the presence of these fats into the side-chains of biological lipids, such as glycerophospholipids, is also essential. We developed a high resolution LC-MS method that quantitatively monitors the major lipid classes found in biospecimens in an efficient, sensitive and robust manner while also characterizing individual lipid side-chains through the use of HCD fragmentation and chromatographic alignment. We herein show how this previously described reversed phase method can baseline separate the cis-trans isomers of phosphatidylglycerol and phosphatidylcholine (PC) with two 18:1 side chains, in both positive and negative mode, as neat solutions and when spiked into a biological matrix. Endogenous PC (18:1/18:1) cis and PC (18:1/18:1) trans isomers were examined in mitochondrial and serum profiling studies, where rats were fed diets enriched in either trans 18:1 fatty acids, or cis 18:1 fatty acids. In this study, we determined the cis:trans isomer ratios of PC (18:1/18:1) and related this ratio to dietary composition. This generalized LC-MS method enables the monitoring of trans fats in biological lipids in the context of a non-targeted method, allowing for relative quantitation and enhanced identification of unknown lipids in complex matrices. PMID:22656324

The efficacy of 9-cis retinoic acid in experimental models of cancer.

PubMed

Gottardis, M M; Lamph, W W; Shalinsky, D R; Wellstein, A; Heyman, R A

1996-01-01

9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemotherapeutic agent. Treatment of the human promyelocytic leukemia cell line HL-60 with 9-cis RA decreases cell proliferation, increases cell differentiation, and increases apoptosis. Induction of apoptosis correlates with an increase in tissue transglutaminase (type II) activity. In vivo, 9-cis RA induces complete tumor regression of an early passage human lip squamous cell carcinoma xenograft. Finally, 9-cis RA inhibits the anchorage-independent growth of the human breast cancer cell lines MCF-7 and LY2 (an antiestrogen-resistant MCF-7 variant). Transient co-transfection assays indicate that 9-cis RA inhibits estrogen receptor transcription of an ERE-tk-LUC reporter through RAR or RXR receptors. These data suggest that retinoid receptors can antagonize estrogen-dependent transcription and provides one possible mechanism for the inhibition of cell growth by 9-cis RA in breast cancer cell lines. In summary, these findings present evidence that 9-cis RA has a wide range of activities in human cancer models.

13-cis retinoic acid and isomerisation in paediatric oncology--is changing shape the key to success?

PubMed

Armstrong, Jane L; Redfern, Christopher P F; Veal, Gareth J

2005-05-01

Retinoic acid isomers have been used with some success as chemotherapeutic agents, most recently with 13-cis retinoic acid showing impressive clinical efficacy in the paediatric malignancy neuroblastoma. The aim of this commentary is to review the evidence that 13-cis retinoic acid is a pro-drug, and consider the implications of retinoid metabolism and isomerisation for the further development of retinoic acid for cancer therapy. The low binding affinity of 13-cis retinoic acid for retinoic acid receptors, low activity in gene expression assays and the accumulation of the all-trans isomer in cells treated with 13-cis retinoic acid, coupled with the more-favourable pharmacokinetic profile of 13-cis retinoic acid compared to other isomers, suggest that intracellular isomerisation to all-trans retinoic acid is the key process underlying the biological activity of 13-cis retinoic acid. Intracellular metabolism of all-trans retinoic acid by a positive auto-regulatory loop may result in clinical resistance to retinoic acid. Agents that block or reduce the metabolism of all-trans retinoic acid are therefore attractive targets for drug development. Devising strategies to deliver 13-cis retinoic acid to tumour cells and facilitate the intracellular isomerisation of 13-cis retinoic acid, while limiting metabolism of all-trans retinoic acid, may have a major impact on the efficacy of 13-cis retinoic acid in paediatric oncology.

Determination of the kinetics of degradation of 13-cis-retinoic acid and all-trans-retinoic acid in solution.

PubMed

Tan, X; Meltzer, N; Lindenbaum, S

1993-09-01

The degradations of 13-cis-retinoic acid and all-trans-retinoic acid in an organic solvent were determined with an HPLC assay. The degradation curves at 70, 50 and 37 degrees C all showed autocatalytic characteristics for both isomers. For this kind of complex reaction, the usual method cannot be used to estimate the shelf-lives and half-lives at room temperature. In this work a new method was developed to directly calculate the shelf-lives and half-lives. From this equation the activation energy was found to change as the multiple step reaction progressed.

The role of 11-cis-retinyl esters in vertebrate cone vision.

PubMed

Babino, Darwin; Perkins, Brian D; Kindermann, Aljoscha; Oberhauser, Vitus; von Lintig, Johannes

2015-01-01

A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim- and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH2), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH2. We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments. © FASEB.

Stimulation of Phospholipid Scrambling of the Erythrocyte Membrane by 9-Cis-Retinoic Acid.

PubMed

Abed, Majed; Alzoubi, Kousi; Lang, Florian; Al Mamun Bhuayn, Abdulla

2017-01-01

The endogenous retinoid 9-cis-retinoic acid has previously been shown to trigger apoptosis in a wide variety of cells including several tumor cells and has thus been suggested for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms participating in the accomplishment of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i) and formation of ceramide. The present study explored, whether 9-cis-retinoic acid induces eryptosis and whether the effect involves Ca2+ and/or ceramide. Flow cytometry was employed to estimate erythrocyte volume from forward scatter, phosphatidylserine exposure at the cell surface from annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was quantified from hemoglobin concentration in the supernatant. A 48 hours exposure of human erythrocytes to 9-cis-retinoic acid (≥ 0.5 µg/ml) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Exposure to 9-cis-retinoic acid (≥ 0.5 µg/ml) significantly increased Fluo3-fluorescence, and the effect of 9-cis-retinoic acid on annexin-V-binding was significantly blunted by removal of extracellular Ca2+. Exposure to 9-cis-retinoic acid (1 µg/ml) further significantly increased the ceramide abundance at the erythrocyte surface and significantly increased hemolysis. 9-cis-retinoic acid triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part downstream of Ca2+ and ceramide. © 2017 The Author(s)Published by S. Karger AG, Basel.

Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood.

PubMed

Vane, F M; Buggé, C J

1981-01-01

The metabolites of 13-cis-retinoic acid (Accutane) were investigated in blood samples from human volunteers on chronic treatment for dermatological disorders. The major metabolite was isolated by reverse-phase high-pressure liquid chromatography and identified as 4-oxo-13-cis-retinoic acid by comparison of its mass and NMR spectra to the spectra of the reference compound. 4-Oxo-all-trans-retinoic acid was also identified, but the extent to which this compound was a metabolite of 13-cis-retinoic acid or an artifactual isomerization product of the major metabolite is unknown. Chromatographic data suggested that small amounts of 13-cis-retinoic acid, 4-hydroxy-13-cis-retinoic acid, and dioxygenated metabolites of 13-cis-retinoic acid may also be present in the blood. This study indicates that a major metabolic pathway of 13-cis-retinoic acid in humans is oxidation at C4 of the cyclohexenyl group.

trans-10,cis-12 Conjugated linoleic acid induces depolarization of mitochondrial membranes in HT-29 human colon cancer cells: a possible mechanism for induction of apoptosis.

PubMed

Cho, Han Jin; Kwon, Gyoo Taik; Park, Jung Han Yoon

2009-10-01

Conjugated linoleic acid (CLA), which is naturally present in a variety of foods such as milk fat and the meat of ruminant animals, has been demonstrated to exert chemoprotective effects in several tissues in experimental animals. CLA is a collective term, which denotes one or more positional and geometric isomers of octadecadienoic acid, with cis-9,trans-11 (c9t11) and trans-10,cis-12 CLA (t10c12) being the principal isomers in commercial preparations. We observed previously that physiological levels of CLA inhibited HT-29 cell growth, and the growth inhibitory effects of CLA were attributed to the effect of t10c12, but not c9t11. In the present study, we assessed the mechanisms by which physiological levels of CLA and t10c12 induce apoptosis in HT-29 cells. HT-29 cells were cultured for 3 days in serum-free medium in the presence of various concentrations of CLA (0-20 micromol/L) or t10c12 (0-4 micromol/L). Addition of CLA or t10c12 to culture medium resulted in a dose-dependent increase in the numbers of apoptotic cells. The results of western blot analysis of total cell lysates showed that CLA and t10c12 increased the levels of cleaved caspase-9, caspase-3, and poly(ADP-ribose) polymerase but did not alter the levels of Bcl-2 family member proteins. However, these fatty acids were shown to increase the translocation of Bad and Bax to the mitochondria, increase mitochondrial membrane permeability, and induce the release of cytochrome c and Smac/Diablo from the mitochondria. In addition, CLA and t10c12 diminished Akt content and Akt phosphorylation. These findings indicate that physiological levels of t10c12 induce apoptosis in HT-29 colon cancer cells, which is mediated via mitochondrion-mediated events associated with a decline in Akt activity, an increase in the translocation of the pro-apototic Bad and Bax to the mitochondria, and the subsequent disruption of normal mitochondrial membrane potential.

Sex Pheromone of the Almond Moth and the Indian Meal Moth: cis-9, trans-12-Tetradecadienyl Acetate.

PubMed

Kuwahara, Y; Kitamura, C; Takashi, S; Hara, H; Ishii, S; Fukami, H

1971-02-26

Female moths of different species but belonging to the same subfamily produce an identical compound as their sex pheromone. The sex pheromone of the almond moth, Cadra cautella (Walker), and the Indian meal moth, Plodia interpunctella (Hübner), has been isolated and identified as cis-9, trans-12-tetradecadienyl acetate.

Studies on long chain cis- and trans-acyl-CoA esters and Acyl-CoA dehydrogenase from rat heart mitochondria.

PubMed

Korsrud, G O; Conacher, H B; Jarvis, G A; Beare-Rogers, J L

1977-02-01

The beta-oxidation of long chain fatty acids was investigated in a preparation of rat heart mitochondria. The acyl-CoA esters of the cis and trans isomers of delta9-hexadecenoic, delta9-octadecenoic, delta11-eicosenoic, and delta13-docosenoic acids were prepared. Rates of the acyl-CoA reaction were determined with an extract from rat heart mitochondria. The apparent Michaelis constant (Km) and maximum velocity (Vmax) were calculated for each substrate. In general, apparent Vmax values decreased with increasing chain length of the monoenoic substrates. Reduced activity of acyl-CoA dehydrogenase with long chain acyl-CoA esters could have contributed to accumulation of lipids in hearts of rats fed diets containing long chain fatty acids.

Conjugated linolenic acid (CLnA), conjugated linoleic acid (CLA) and other biohydrogenation intermediates in plasma and milk fat of cows fed raw or extruded linseed.

PubMed

Akraim, F; Nicot, M C; Juaneda, P; Enjalbert, F

2007-07-01

Thirty lactating dairy cows were used in a 3 × 3 Latin-square design to investigate the effects of a raw or extruded blend of linseed and wheat bran (70:30) on plasma and milk fatty-acids (FA). Linseed diets, containing 16.6% linseed blend on a dry-matter basis, decreased milk yield and protein percentage. They decreased the proportions of FA with less than 18 carbons in plasma and milk and resulted in cis-9, cis-12, cis-15 18:3 proportions that were more than three and four times higher in plasma and milk, respectively, whereas cis-9, cis-12 18:2 proportions were decreased by 10-15%. The cis-9, trans-11, cis-15 18:3 isomer of conjugated linolenic acid was not detected in the milk of control cows, but was over 0.15% of total FA in the milk fat of linseed-supplemented cows. Similarly, linseed increased plasma and milk proportions of all biohydrogenation (BH) intermediates in plasma and milk, including the main isomer of conjugated linoleic acid cis-9, trans-11 18:2, except trans-4 18:1 and cis-11, trans-15 18:2 in plasma lipids. In milk fat, compared with raw linseed, extruded linseed further reduced 6:0-16:0 even-chain FA, did not significantly affect the proportions of 18:0, cis-9 18:1 and cis-9, cis-12 18:2, tended to increase cis-9, cis-12, cis-15 18:3, and resulted in an additional increase in the proportions of most BH intermediates. It was concluded that linseed addition can improve the proportion of conjugated linoleic and linolenic acids, and that extrusion further increases the proportions of intermediates of ruminal BH in milk fat.

The cis/trans isomerization of the double bond of a fatty acid as a strategy for adaptation to changes in ambient temperature in the psychrophilic bacterium, Vibrio sp. strain ABE-1.

PubMed

Okuyama, H; Okajima, N; Sasaki, S; Higashi, S; Murata, N

1991-06-19

The major phospholipid, phosphatidylethanolamine (PE), of Vibrio sp. strain ABE-1 contains a unique trans-unsaturated fatty acid, 9-trans-hexadecenoic acid (16:1(9t], at the sn-2 position of the glycerol moiety. The major molecular species of PE that contain 16:1(9t) at the sn-2 position have either 9-cis-hexadecenoic acid (16:1(9c] or hexadecanoic acid (16:0) at the sn-1 position. The transition temperatures of the liquid-crystal to the gel phase of 16:1(9c)/16:1(9t)-PE and 16:0/16:1(9t)-PE were -3 degrees C and 38 degrees C, respectively, temperatures that were 31 degrees C and 18 degrees C higher than the corresponding temperatures for 16:1(9c)/16:1(9c)-PE and 16:0/16:1(9c)-PE. The proportion of 16:1(9c)/16:1(9t)-PE and 16:0/16:1(9t)-PE increased significantly in cells grown at 20 degrees C over that in cells grown at 5 degrees C. When cells grown at 5 degrees C were incubated at 20 degrees C in the presence of cerulenin, an inhibitor of the synthesis de novo of fatty acids, the level of 16:1(9t) increased almost in parallel with a concomitant decrease in the level of 16:1(9c) at the sn-2 position. These results suggest that 16:1(9c) is converted to 16:1(9t) by the cis/trans isomerization of the double bond in the fatty acid. This conversion is discussed as a possible strategy for adaptation by bacteria to changes in temperature.

Thermal cis-trans isomerization of cis,cis-3,7-decadiene - A model for cis-1,4-polybutadiene

NASA Technical Reports Server (NTRS)

Golub, M. A.; Lee, W. M.

1983-01-01

The thermal cis-trans isomerization of cis,cis-3,7-decadiene (DD), a model compound for cis-PBD, is reported. It is demonstrated that the rather low E for the polyalkenamer isomerizations compared with that for the 2-olefins is not an artifact of the solid polymer structures, but rather is characteristic of both small and large molecules possessing pairs of nonconjugated vinylene double bonds in a suitable arrangement.

Characterization of cis- and trans-octadecenoic acid positional isomers in edible fat and oil using gas chromatography-flame ionisation detector equipped with highly polar ionic liquid capillary column.

PubMed

Yoshinaga, Kazuaki; Asanuma, Masaharu; Mizobe, Hoyo; Kojima, Koichi; Nagai, Toshiharu; Beppu, Fumiaki; Gotoh, Naohiro

2014-10-01

In this study, the characterisation of all cis- and trans-octadecenoic acid (C18:1) positional isomers in partially hydrogenated vegetable oil (PHVO) and milk fat, which contain several cis- and trans-C18:1 positional isomers, was achieved by gas chromatography-flame ionisation detector equipped with a highly polar ionic liquid capillary column (SLB-IL111). Prior to analysis, the cis- and trans-C18:1 fractions in PHVO and milk fat were separated using a silver-ion cartridge. The resolution of all cis-C18:1 positional isomers was successfully accomplished at the optimal isothermal column temperature of 120 °C. Similarly, the positional isomers of trans-C18:1, except for trans-6-C18:1 and trans-7-C18:1, were separated at 120 °C. The resolution of trans-6-C18:1 and trans-7-C18:1 isomers was made possible by increasing the column temperature to 160 °C. This analytical method is suitable for determining the cis- and trans-C18:1 positional isomers in edible fats and oils. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT)

PubMed Central

Kaylor, Joanna J.; Cook, Jeremy D.; Makshanoff, Jacob; Bischoff, Nicholas; Yong, Jennifer; Travis, Gabriel H.

2014-01-01

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action. PMID:24799687

Occurrence of trans monounsaturated and polyunsaturated fatty acids in Colwellia psychrerythraea strain 34H.

PubMed

Hashimoto, Mikako; Orikasa, Yoshitake; Hayashi, Hidenori; Watanabe, Kentaro; Yoshida, Kiyohito; Okuyama, Hidetoshi

2015-07-01

Colwellia psychrerythraea strain 34H is an obligately psychrophilic bacterium that has been used as a model cold-adapted microorganism because of its psychrophilic growth profile, significant production of cold-active enzymes, and cryoprotectant extracellular polysaccharide substances. However, its fatty acid components, particularly trans unsaturated fatty acids and long-chain polyunsaturated fatty acids (LC-PUFAs), have not been fully investigated. In this study, we biochemically identified Δ9-trans hexadecenoic acid [16:1(9t)] and LC-PUFAs such as docosahexaenoic acid. These results are comparable with the fact that the strain 34H genome sequence includes pfa and cti genes that are responsible for the biosynthesis of LC-PUFAs and trans unsaturated fatty acids, respectively. Strain 34H cells grown under static conditions at 5 °C had higher levels of 16:1(9t) than those grown under shaken conditions, and this change was accompanied by an antiparallel decrease in the levels of Δ9-cis hexadecenoic acid [16:1(9c)], suggesting that the cis-to-trans isomerization reaction of 16:1(9c) is activated under static (microanaerobic) culture conditions, that is, the enzyme could be activated by the decreased dissolved oxygen concentration of cultures. On the other hand, the levels of LC-PUFAs were too low (less than 3% of the total), even for cells grown at 5 °C, to evaluate their cold-adaptive function in this bacterium. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids.

PubMed

Sauvat, Allan; Chen, Guo; Müller, Kevin; Tong, Mingming; Aprahamian, Fanny; Durand, Sylvère; Cerrato, Giulia; Bezu, Lucillia; Leduc, Marion; Franz, Joakim; Rockenfeller, Patrick; Sadoshima, Junichi; Madeo, Frank; Kepp, Oliver; Kroemer, Guido

2018-04-01

Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.

c9t11-Conjugated linoleic acid-rich oil fails to attenuate wasting in colon-26 tumor-induced late-stage cancer cachexia in male CD2F1 mice.

PubMed

Tian, Min; Kliewer, Kara L; Asp, Michelle L; Stout, Michael B; Belury, Martha A

2011-02-01

Cancer cachexia is characterized by muscle and adipose tissue wasting caused partly by chronic, systemic inflammation. Conjugated linoleic acids (CLAs) are a group of fatty acids with various properties including anti-inflammatory cis9, trans11 (c9t11)-CLA and lipid-mobilizing trans10, cis12 (t10c12)-CLA. The purpose of this study was to test whether dietary supplementation of a c9t11-CLA-rich oil (6:1 c9t11:t10c12) could attenuate wasting of muscle and adipose tissue in colon-26 adenocarcinoma-induced cachexia in mice. Loss of body weight, muscle and adipose tissue mass caused by tumors were not rescued by supplementation with the c9t11-CLA-rich oil. In quadriceps muscle, c9t11-CLA-rich oil exacerbated tumor-induced gene expression of inflammatory markers tumor necrosis factor-α, IL-6 receptor and the E3 ligase MuRF-1 involved in muscle proteolysis. In epididymal adipose tissue, tumor-driven delipidation and atrophy was aggravated by the c9,t11-CLA-rich oil, demonstrated by further reduced adipocyte size and lower adiponectin expression. However, expression of inflammatory cytokines and macrophage markers were not altered by tumors, or CLA supplementation. These data suggest that addition of c9t11-CLA-rich oil (0.6% c9t11, 0.1% t10c12) in diet did not ameliorate wasting in mice with cancer cachexia. Instead, it increased expression of inflammatory markers in the muscle and increased adipose delipidation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of Infrared Laser Radiation on the In Vitro Isomerization of All-Trans Retinal to 11-Cis Retinal

PubMed Central

Liegner, J.; Taboada, J.; Tsin, A. T. C.

2015-01-01

The in vitro effect of infrared laser light on the isomerization of all-trans retinal dissolved in an ether/hexane and also an ethanol solvent was studied. Pulsed laser energy at 1064 nm was used to drive the molecular reconfiguration of all-trans retinal to 11-cis retinal. High pressure liquid chromatography (HPLC) was used to quantify the conversion. Overall isomerization was minimal (0.2 percent to 1.0 percent), yet, a significant difference in isomerization due to pulsed infrared laser energy over non-modulated monochromatic laser light was detected (up to 168 percent difference). Potentially, pulsed laser radiation tuned to the ethylenic stretch frequency of the C11=C12 bond of retinal may induce rotational changes to the chromophore. PMID:26321787

Accurate millimetre and submillimetre rest frequencies for cis- and trans-dithioformic acid, HCSSH

NASA Astrophysics Data System (ADS)

Prudenzano, D.; Laas, J.; Bizzocchi, L.; Lattanzi, V.; Endres, C.; Giuliano, B. M.; Spezzano, S.; Palumbo, M. E.; Caselli, P.

2018-04-01

Context. A better understanding of sulphur chemistry is needed to solve the interstellar sulphur depletion problem. A way to achieve this goal is to study new S-bearing molecules in the laboratory, obtaining accurate rest frequencies for an astronomical search. We focus on dithioformic acid, HCSSH, which is the sulphur analogue of formic acid. Aims: The aim of this study is to provide an accurate line list of the two HCSSH trans and cis isomers in their electronic ground state and a comprehensive centrifugal distortion analysis with an extension of measurements in the millimetre and submillimetre range. Methods: We studied the two isomers in the laboratory using an absorption spectrometer employing the frequency-modulation technique. The molecules were produced directly within a free-space cell by glow discharge of a gas mixture. We measured lines belonging to the electronic ground state up to 478 GHz, with a total number of 204 and 139 new rotational transitions, respectively, for trans and cis isomers. The final dataset also includes lines in the centimetre range available from literature. Results: The extension of the measurements in the mm and submm range lead to an accurate set of rotational and centrifugal distortion parameters. This allows us to predict frequencies with estimated uncertainties as low as 5 kHz at 1 mm wavelength. Hence, the new dataset provided by this study can be used for astronomical search. Frequency lists are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/612/A56

On-line concentration and determination of all-trans- and 13-cis- retinoic acids in rabbit serum by application of sweeping technique in micellar electrokinetic chromatography.

PubMed

Zhao, Yongxi; Kong, Yu; Wang, Bo; Wu, Yayan; Wu, Hong

2007-03-30

A simple and rapid micellar electrokinetic chromatography (MEKC) method with UV detection was developed for the simultaneous separation and determination of all-trans- and 13-cis-retinoic acids in rabbit serum by on-line sweeping concentration technique. The serum sample was simply deproteinized and centrifuged. Various parameters affecting sample enrichment and separation were systematically investigated. Under optimal conditions, the analytes could be well separated within 17min, and the relative standard deviations (RSD) of migration times and peak areas were less than 3.4%. Compared with the conventional MEKC injection method, the 18- and 19-fold improvements in sensitivity were achieved, respectively. The proposed method has been successfully applied to the determination of all-trans- and 13-cis-retinoic acids in serum samples from rabbits and could be feasible for the further pharmacokinetics study of all-trans-retinoic acid.

Saturated and cis- and trans-unsaturated fatty acids intake in rural and urban Costa Rican adolescents.

PubMed

Monge-Rojas, Rafael; Campos, Hannia; Fernández Rojas, Xinia

2005-08-01

The purpose of this study is to determine whether intake of saturated fatty acids and cis- and trans-unsaturated fatty acids is associated with an urban compared to a rural lifestyle, and whether these associations are responsible for differences in plasma lipid concentrations. Two hundred seventy-five adolescents, aged 12 to 19 years, living in rural and urban areas of San José, Costa Rica, were included in the study. All participants completed three-day food records, provided a fasting blood sample, and carried out a modified Harvard Step Test. Compared to rural, urban adolescents reported higher intakes of energy-adjusted individual and total saturated fatty acids, total n-3, total n-6 (p < 0.05). Compared to rural, urban adolescents had higher intake of 18:1 (3.65 vs. 3.25, p = 0.0001) and 18:2 (0.62 vs. 0.80, p = 0.001) trans fatty acids, as well as lower intake of carbohydrate (p < 0.05). Palm shortening was the main source of saturated fat (32%), and partially hydrogenated soybean oil used for cooking was the main source of n-3 fatty acids (33%), n-6 fatty acids (33%) and trans fatty acids (34%). Compared to rural, urban adolescents had lower systolic and diastolic blood pressure and higher plasma HDL cholesterol concentration (44 vs. 40 mg/dL, p < 0.0001), but were more likely to be sedentary (68% vs. 57%, p < 0.0001). Among environmental factors, higher carbohydrate intake was a significant determinant of a lower HDL cholesterol (beta coeff = -1.45, p = 0.04), while lauric and myristic fatty acids correlated with increased LDL cholesterol (beta coeff = 3.6, 1.7, p < 0.05). A diet containing less carbohydrate and less saturated fatty acids contributes to a more beneficial lipid profile in Costa Rican adolescents, but a trend towards high trans fatty acids intake, particularly in the urban area, is worrisome given the well-known adverse effects of trans fatty acids.

Comparative effects of conjugated linoleic acid (CLA) and linoleic acid (LA) on the oxidoreduction status in THP-1 macrophages.

PubMed

Rybicka, Marta; Stachowska, Ewa; Gutowska, Izabela; Parczewski, Miłosz; Baśkiewicz, Magdalena; Machaliński, Bogusław; Boroń-Kaczmarska, Anna; Chlubek, Dariusz

2011-04-27

The aim of this study was to investigate the effect of conjugated linoleic acids (CLAs) on macrophage reactive oxygen species synthesis and the activity and expression of antioxidant enzymes, catalase (Cat), glutathione peroxidase (GPx), and superoxide dismutase (SOD). The macrophages were obtained from the THP-1 monocytic cell line. Cells were incubated with the addition of cis-9,trans-11 CLA or trans-10,cis-12 CLA or linoleic acid. Reactive oxygen species (ROS) formation was estimated by flow cytometry. Enzymes activity was measured spectrophotometrically. The antioxidant enzyme mRNA expression was estimated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was based on nonparametric statistical tests [Friedman analysis of variation (ANOVA) and Wilcoxon signed-rank test]. cis-9,trans-11 CLA significantly increased the activity of Cat, while trans-10,cis-12 CLA notably influenced GPx activity. Both isomers significantly decreased mRNA expression for Cat. Only trans-10,cis-12 significantly influenced mRNA for SOD-2 expression. The CLAs activate processes of the ROS formation in macrophages. Adverse metabolic effects of each isomer action were observed.

[Influence of conjugated linoleic acids on metabolic processes in cells and tissues].

PubMed

Siwiec, Ewa; Stachowska, Ewa

2017-01-01

Conjugated linoleic acids (CLA) are constitutional and geometric isomers of this acid. The most commonly consumed geometric isomers are cis-9,trans-11 (c9, t11) CLA and trans-10, cis-12 (t10,c12) CLA. These isomers together with trans-9,trans-11 CLA and trans-10,trans-12 CLA constitute about 90% of all CLA in natural products. Different structure of the isomers affects their functions in the body. Differences in the effects on organs and tissues are sometimes small and sometimes opposed, sometimes the isomers work synergistically. Diverse influence has been shown mainly in neoplastic processes and lipid metabolism. For example, differences in inhibition of proliferation of prostate cancer cells are explained by different pathways: t10,c12 CLA acts on apoptosis and cell cycle control genes, while c9,t11 CLA regulates genes involved in metabolism of arachidonic acid with subsequent impairment of eicosanoids synthesis. Other studies have shown that t10,c12 CLA, but not c9,t11 CLA, can induce fat reduction in adipose tissue and apoptosis of adipocytes in mice.

PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats

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

Willemin, Marie-Emilie; Sorbonne University, Université de Technologie de Compiègne, CNRS, UMR 7338 Biomechanics and Bioengineering, Centre de recherche Royallieu CS 60319,60203 Compiègnee Cedex; Desmots, Sophie

2016-03-01

Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acidmore » (3-PBA) and 4′OH-phenoxybenzoic acid (4′-OH-PBA). In vivo experiments performed in Sprague–Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-permethrin, respectively. High concentrations of the metabolite 4′-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine. - Highlights: • A PBPK model of isomers of permethrin and its urinary metabolites was developed. • A quantitative link was established for permethrin and its biomarkers of exposure. • The bayesian framework allows getting confidence interval on the estimated parameters. • The PBPK model can be

Determination of trans- and cis-urocanic acid in relation to histamine, putrescine, and cadaverine contents in tuna (Auxis Thazard) at different storage temperatures.

PubMed

Zare, Davood; Muhammad, Kharidah; Bejo, Mohd Hair; Ghazali, H M

2015-02-01

Scombroid fish poisoning is usually associated with consumption of fish containing high levels of histamine. However, reports indicate that some cases have responded to antihistamine therapy while ingested histamine levels in these cases were low. Potentiation of histamine toxicity by some biogenic amines, and release of endogenous histamine by other compounds such as cis-urocanic acid (UCA) are some hypotheses that have been put forth to explain this anomaly. Very little is known about the effects of storage conditions on the production of both UCA isomers and biogenic amines in tuna. Thus, the production of trans- and cis-UCA, histamine, putrescine, and cadaverine in tuna during 15 d of storage at 0, 3, and 10 °C and 2 d storage at ambient temperature were monitored. The initial trans- and cis-UCA contents in fresh tuna were 2.90 and 1.47 mg/kg, respectively, whereas the levels of putrescine and cadaverine were less than 2 mg/kg, and histamine was not detected. The highest levels of trans- and cis-UCA were obtained during 15 d storage at 3 °C (23.74 and 21.79 mg/kg, respectively) while the highest concentrations of histamine (2796 mg/kg), putrescine (220.32 mg/kg) and cadaverine (1045.20 mg/kg) were obtained during storage at room temperature, 10 and 10 °C, respectively. Histamine content increased considerably during storage at 10 °C whereas trans- and cis-UCA contents changed slightly. The initial trans-UCA content decreased during storage at ambient temperature. Thus, unlike histamine, concentrations of trans- and cis-UCA did not result in elevated levels during storage of tuna. © 2015 Institute of Food Technologists®

Isolation of pyrrolocins A-C: cis- and trans-decalin tetramic acid antibiotics from an endophytic fungal-derived pathway.

PubMed

Jadulco, Raquel C; Koch, Michael; Kakule, Thomas B; Schmidt, Eric W; Orendt, Anita; He, Haiyin; Janso, Jeffrey E; Carter, Guy T; Larson, Erica C; Pond, Christopher; Matainaho, Teatulohi K; Barrows, Louis R

2014-11-26

Three new decalin-type tetramic acid analogues, pyrrolocins A (1), B (2), and C (3), were defined as products of a metabolic pathway from a fern endophyte, NRRL 50135, from Papua New Guinea. NRRL 50135 initially produced 1 but ceased its production before chemical or biological evaluation could be completed. Upon transfer of the biosynthetic pathway to a model host, 1-3 were produced. All three compounds are structurally related to equisetin-type compounds, with 1 and 3 having a trans-decalin ring system, while 2 has a cis-fused decalin. All were active against Mycobacterium tuberculosis, with the trans-decalin analogues 1 and 3 exhibiting lower MICs than the cis-decalin analogue 2. Here we report the isolation, structure elucidation, and antimycobacterial activities of 1-3 from the recombinant expression as well as the isolation of 1 from the wild-type fungus NRRL 50135.

Examination of the persistency of milk fatty acid composition responses to fish oil and sunflower oil in the diet of dairy cows.

PubMed

Shingfield, K J; Reynolds, C K; Hervás, G; Griinari, J M; Grandison, A S; Beever, D E

2006-02-01

Based on the potential benefits of cis-9, trans-11 conjugated linoleic acid (CLA) for human health, there is a need to develop effective strategies for enhancing milk fat CLA concentrations. Levels of cis-9, trans-11 CLA in milk can be increased by supplements of fish oil (FO) and sunflower oil (SO), but there is considerable variation in the response. Part of this variance may reflect time-dependent ruminal adaptations to high levels of lipid in the diet, which lead to alterations in the formation of specific biohydrogenation intermediates. To test this hypothesis, 16 late lactation Holstein-British Friesian cows were used in a repeated measures randomized block design to examine milk fatty acid composition responses to FO and SO in the diet over a 28-d period. Cows were allocated at random to corn silage-based rations (8 per treatment) containing 0 (control) or 45 g of oil supplement/kg of dry matter consisting (1:2; wt/wt) of FO and SO (FSO), and milk composition was determined on alternate days from d 1. Compared with the control, the FSO diet decreased mean dry matter intake (21.1 vs. 17.9 kg/d), milk fat (47.7 vs. 32.6 g/kg), and protein content (36.1 vs. 33.3 g/kg), but had no effect on milk yield (27.1 vs. 26.4 kg/d). Reductions in milk fat content relative to the FSO diet were associated with increases in milk trans-10 18:1, trans-10, cis-12 CLA, and trans-9, cis-11 CLA concentrations (r(2) = 0.74, 0.57, and 0.80, respectively). Compared with the control, the FSO diet reduced milk 4:0 to 18:0 and cis 18:1 content and increased trans 18:1, trans 18:2, cis-9, trans-11 CLA, 20:5 n-3, and 22:6 n-3 concentrations. The FSO diet caused a rapid elevation in milk cis-9, trans-11 CLA content, reaching a maximum of 5.37 g/100 g of fatty acids on d 5, but these increases were transient, declining to 2.35 g/100 g of fatty acids by d 15. They remained relatively constant thereafter. Even though concentrations of trans-11 18:1 followed the same pattern of temporal

A chiral HPLC method for the simultaneous separation of configurational isomers of the predominant cis/trans forms of astaxanthin.

PubMed

Abu-Lafi, S; Turujman, S A

1997-01-01

We report an HPLC method that allows the simultaneous separation of configurational isomers of the predominant cis/trans forms of astaxanthin. The configurational isomers of the all-trans-, and most of the configurational isomers of the 9-cis-, 13-cis- and 15-cis-astaxanthin were separated on a Sumichiral OA-2000 column, which is manufactured and packed in Japan with a Pirkle covalent D-phenylglycine chiral stationary phase (CSP). The large separation of the cis isomers from the all-trans isomers that we report here ensure the suitability of this method for the routine determination of the ratio of the configurational isomers of all-trans-astaxanthin.

13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes.

PubMed

Nelson, Amanda M; Gilliland, Kathryn L; Cong, Zhaoyuan; Thiboutot, Diane M

2006-10-01

Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.

Molecular dynamics simulations of trans- and cis- N-acetyl- N'-methylamides of XaaPro dipeptides

NASA Astrophysics Data System (ADS)

Hoon Choi, Seung; Yun Yu, Jeong; Kwang Shin, Jae; Shik Jhon, Mu

1994-07-01

The occurrence of cis imide bonds in proteins is much higher than that of cis amide bonds due to the unique properties of proline. In order to examine the relationship between the high occurrence of these cis imide bonds and the residues preceding the proline, we perform molecular dynamics simulations of trans- and cis- N-acetyl- N'-methylamides of XaaPro dipeptides (AcXaaProNHMe). We investigate the conformational energies and structures of trans- and cis-AcXaa where Xaa has 12 amino acids in the vacuum state and 5 amino acids in the solution state. It is found that the occurrence of the cis imide bonds is strongly affected by the residue preceding the proline, and the dihedral angles (φ,ψ) of the backbone in AcXaaProNHMe are influenced by the configuration of the imide bond. We also find that the equilibrium properties of XaaPro in solution simulations are more similar to the statistics of X-ray crystallographic data than are those in vacuum simulations and solvation causes a remarkable change in the conformation of the pyrrolidine ring from the endo to the exo form.

Visual pigments. 11. Spectroscopy and photophysics of retinoic acids and all-trans-methyl retinoate. [Photophysical properties at 77/sup 0/K

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

Takemura, T.; Chihara, K.; Becker, R.S.

1980-04-09

The photophysics of hydrogen-bonded complexes of retinoic acid and its 9-cis and 13-cis isomers and the photophysics of the dimers of these isomers of retinoic acid were studied. The investigation indicated that complexes of retinoic acid and molecules that form hydrogen bonds with the carbonyl oxygen of retinoic acid (type I complexes) have both higher radiative and nonradiative rate constants than do hydrogen-bonded complexes of retinoic acid and molecules that form hydrogen bonds only with the hydroxyl oxygen of retinoic acid (type II complexes). For all-trans-retinoic acid in 3-methylpentane at 77 K, the type I complexes have radiative rate constantsmore » approximately equal to or greater than 2 x 10/sup 8/ s/sup -1/ and nonradiative rate constants greater than 3 x 10/sup 8/ s/sup -1/. Both the radiative and nonradiative rate constants of the type II complexes of all-trans-retinoic acid at 77 K in 3-methylpentane are less than 1 x 10/sup 8/ s/sup -1/. The dimer of retinoic acid (K(association) = 1 x 10/sup 4/ M/sup -1/ at room temperature for the all-trans isomer) behaves like a type I complex, and its excited-state properties are better understood in terms of hydrogen bonding than in terms of an exciton model. The photophysical properties and triplet-triplet absorption spectrum of methyl retinoate were measured. The study concluded with an examination of some of the implications of this work for the role of hydrogen bonding in the dimers and monomers of retinal and retinol.« less

Photodissociation of cis-, trans-, and 1,1-dichloroethylene in the ultraviolet range: characterization of Cl((2)P(J)) elimination.

PubMed

Hua, Linqiang; Zhang, Xiaopeng; Lee, Wei-Bin; Chao, Meng-Hsuan; Zhang, Bing; Lin, King-Chuen

2010-01-14

By using photofragment velocity imaging detection coupled with a (2 + 1) resonance-enhanced multiphoton ionization technique, the elimination channel of spin-orbit chlorine atoms in photodissociation of cis-, trans-, and 1,1-dichloroethylene at two photolysis wavelengths of 214.5 and 235 nm is investigated. Translational energy and angular distributions of Cl((2)P(J)) fragmentation are acquired. The Cl((2)P(J)) fragments are produced by two competing channels. The fast dissociation component with higher translational energy is characterized by a Gaussian distribution, resulting from a curve crossing of the initially excited (pi, pi*) state to nearby repulsive (pi, sigma*) and/or (n, sigma*). In contrast, the slow component with a lower translational energy is characterized by a Boltzmann distribution, which dissociates on the vibrationally hot ground state relaxed from the (pi, pi*) state via internal conversion. cis-C(2)H(2)Cl(2) is found to have a larger branching of Boltzmann component than the other two isomers. The fraction of available energy partitioning into translation increases along the trend of cis- < trans- < 1,1-C(2)H(2)Cl(2). This trend may be fitted by a rigid radical model and interpreted by means of a torque generated during the C-Cl bond cleavage. The anisotropy parameters are determined, and the transition dipole moments are expected to be essentially along the C horizontal lineC bond axis. The results are also predicted theoretically. The relative quantum yields of Cl((2)P(J)) have a similar value for the three isomers at the two photolysis wavelengths.

Differentiation of refined and virgin edible oils by means of the trans- and cis-phytol isomer distribution.

PubMed

Vetter, Walter; Schröder, Markus; Lehnert, Katja

2012-06-20

The differentiation of nonrefined (e.g., cold-pressed) and refined edible oils is an important task in food control because of the higher commercial value of the former. Here, we explored the suitability of the relative abundance of cis-phytol as a marker for authentication of nonrefined edible oils. Phytol, the tetramethyl-branched, monoenoic alcohol, is found widespread in nature as a part of chlorophyll. In chlorophyll, only trans-phytol is found. In this study, we present a method for the analysis of the phytol isomers, considering that traces of cis-phytol (contributing 0.1% to the phytol content) can be determined next to trans-phytol. For this purpose, phytol was gathered with the unsaponifiable matter from the oil, trimethylsilylated, and analyzed by gas chromatography coupled to mass spectrometry. With this method, 27 samples of edible oils (16 refined and 11 nonrefined edible oils) were analyzed for the abundance of cis-phytol relative to trans-phytol. In the nonrefined oils (e.g., olive oil, rapeseed oil, maize oil, and sunflower oil), cis-phytol contributed 0.1% (n = 3) or less (n = 8) to the phytol content. In contrast, the refined olive oils (n = 4) contained a share of 1.3-3% cis-phytol; the refined rapeseed oil (n = 3) contained a share of 0.7-1.0% cis-phytol; and the refined sunflower oil (n = 4) contained a share of 0.3-0.9% cis-phytol. Only one refined pomegranate kernel did not contain cis-phytol. The phytol concentration was not suited to distinguish nonrefined from refined oils. In contrast, our data suggest that the virtual absence of cis-phytol can be used as a marker for nonrefined (e.g., cold-pressed) edible oils.

Reactivity and biological properties of a series of cytotoxic PtI2(amine)2 complexes, either cis or trans configured.

PubMed

Messori, Luigi; Cubo, Leticia; Gabbiani, Chiara; Álvarez-Valdés, Amparo; Michelucci, Elena; Pieraccini, Giuseppe; Ríos-Luci, Carla; León, Leticia G; Padrón, José M; Navarro-Ranninger, Carmen; Casini, Angela; Quiroga, Adoración G

2012-02-06

Six diiodido-diamine platinum(II) complexes, either cis or trans configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the trans isomers being, generally, more effective than their cis counterparts. Cell cycle analysis revealed different modes of action for these new Pt(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that trans complexes preferentially release their iodide ligands upon biomolecule binding, while the cis isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles.

40 CFR 721.2250 - 1,4-Cyclohexanediamine, cis- and trans-.

Code of Federal Regulations, 2011 CFR

2011-07-01

... § 721.125 (a), (b), (c), (f), (g), (h), (i), and (k) are applicable to manufacturers, importers, and... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,4-Cyclohexanediamine, cis- and trans... Substances § 721.2250 1,4-Cyclohexanediamine, cis- and trans-. (a) Chemical substances and significant new...

Hydroperoxide-dependent cooxidation of 13-cis-retinoic acid by prostaglandin H synthase.

PubMed

Samokyszyn, V M; Marnett, L J

1987-10-15

Reverse phase high pressure liquid chromatography was employed to separate the major products resulting from the hydroperoxide-dependent cooxidation of 13-cis-retinoic acid by microsomal and purified prostaglandin H (PGH) synthase. Several major oxygenated metabolites including 4-hydroxy-, 5,6-epoxy-, and 5,8-oxy-13-cis-retinoic acid were unambiguously identified on the basis of cochromatography with authentic standards, uv spectra, and mass spectral analysis. Identical product profiles were generated regardless of the type of oxidizing substrate employed, and heat-denatured microsomes or enzyme did not support oxidation. In addition, several geometric isomers including all trans-retinoic acid were identified. Isomerization to all trans-retinoic acid in microsomes occurred in the absence of exogenous hydroperoxide, was insensitive to inhibition by antioxidant, and was eliminated when heat-denatured preparations were substituted for intact microsomes. Conversely, isomerization to at least one other isomer required the addition of hydroperoxide and was sensitive to antioxidant inhibition. Addition of antioxidant to microsomal incubation mixtures inhibited the hydroperoxide-dependent generation of 5,6-epoxy- and 5,8-oxy-13-cis-retinoic acid and other oxygenated metabolites but stimulated the formation of 4-hydroxy-13-cis-retinoic acid. Under standard conditions, 77% of the original retinoid was metabolized resulting in products containing 1.25 oxygen atoms/oxygenated metabolite, and two dioxygen molecules were consumed per hydroperoxide reduced. Purified PGH synthase also supported O2 uptake during cooxidation of 13-cis-retinoic acid by H2O2 or 5-phenyl-4-pentenyl-1-hydroperoxide, and the initial velocities of O2 uptake were directly proportional to enzyme concentration. 13-cis-Retinoic acid effectively inhibited peroxidase-dependent cooxidation of guaiacol indicating a direct interaction of retinoid with peroxidase iron-oxo intermediates, and EPR spin trapping

Thermal degradation kinetics of all-trans and cis-carotenoids in a light-induced model system.

PubMed

Xiao, Ya-Dong; Huang, Wu-Yang; Li, Da-Jing; Song, Jiang-Feng; Liu, Chun-Quan; Wei, Qiu-Yu; Zhang, Min; Yang, Qiu-Ming

2018-01-15

Thermal degradation kinetics of lutein, zeaxanthin, β-cryptoxanthin, β-carotene was studied at 25, 35, and 45°C in a model system. Qualitative and quantitative analyses of all-trans- and cis-carotenoids were conducted using HPLC-DAD-MS technologies. Kinetic and thermodynamic parameters were calculated by non-linear regression. A total of 29 geometrical isomers and four oxidation products were detected, including all-trans-, keto compounds, mono-cis- and di-cis-isomers. Degradations of all-trans-lutein, zeaxanthin, β-cryptoxanthin, and β-carotene were described by a first-order kinetic model, with the order of rate constants as k β -carotene >k β -cryptoxanthin >k lutein >k zeaxanthin . Activation energies of zeaxanthin, lutein, β-cryptoxanthin, and β-carotene were 65.6, 38.9, 33.9, and 8.6kJ/moL, respectively. cis-carotenoids also followed with the first-order kinetic model, but they did not show a defined sequence of degradation rate constants and activation energies at different temperatures. A possible degradation pathway of four carotenoids was identified to better understand the mechanism of carotenoid degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP).

PubMed

Grimm, Marcus O W; Rothhaar, Tatjana L; Grösgen, Sven; Burg, Verena K; Hundsdörfer, Benjamin; Haupenthal, Viola J; Friess, Petra; Kins, Stefan; Grimm, Heike S; Hartmann, Tobias

2012-10-01

Hydrogenation of oils and diary products of ruminant animals leads to an increasing amount of trans fatty acids in the human diet. Trans fatty acids are incorporated in several lipids and accumulate in the membrane of cells. Here we systematically investigate whether the regulated intramembrane proteolysis of the amyloid precursor protein (APP) is affected by trans fatty acids compared to the cis conformation. Our experiments clearly show that trans fatty acids compared to cis fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP, resulting in an increased production of amyloid beta (Aβ) peptides, main components of senile plaques, which are a characteristic neuropathological hallmark for Alzheimer's disease (AD). Moreover, our results show that oligomerization and aggregation of Aβ are increased by trans fatty acids. The mechanisms identified by this in vitro study suggest that the intake of trans fatty acids potentially increases the AD risk or causes an earlier onset of the disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Structural Determination and Occurrence in Ahiflower Oil of Stearidonic Acid Trans Fatty Acids.

PubMed

Delmonte, Pierluigi; Milani, Andrea; Bhangley, Shivani

2018-02-01

Several marine oils and seed oils on the market contain relevant quantities of stearidonic acid (18:4n-3, SDA). The formation of 18:4n-3 trans fatty acids (tFA) during the refining of these oils necessitates the development of a method for their quantification. In this study, 18:4n-3 was isolated from Ahiflower and isomerized to obtain its 16 geometric isomers. The geometric isomers of 18:4n-3 were isolated by silver ion HPLC (Ag + -HPLC) and characterized by partial reduction with hydrazine followed by gas chromatography analysis. The elution order of all 16 isomers was established using a 100 m × 0.25 mm 100% poly(biscyanopropyl siloxane) capillary column and at the elution temperature of 180 °C. The 4 mono-trans-18:4n-3 isomers produced during the refining of oils rich in 18:4n-3 were chromatographically resolved from each other, but c6,t9,c12,c15-18:4 coeluted with the tetra-cis isomer. These 2 fatty acids (FA) were resolved by reducing the separation temperature to 150 °C, but this change caused tetra-cis-18:4n-3 to coelute with t6,c9,c12,c15-18:4. Combining the results from 2 isothermal separations (180 and 150 °C) was necessary to quantify the 4 mono-trans 18:4n-3 FA in Ahiflower oil. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Effects of dietary cis and trans unsaturated and saturated fatty acids on the glucose metabolites and enzymes of rats.

PubMed

Bernal, Claudio A; Rovira, Jordi; Colandré, María E; Cussó, Roser; Cadefau, Joan A

2006-05-01

The aim of the present study was to examine whether the level of dietary cis fatty acid (cFA), or the isomers (trans or cis) and/or the saturation of the fatty acids at high dietary fat levels altered the intracellular glucose metabolites and certain regulatory enzyme activities in the skeletal muscle and liver of rats. The animals were fed for 30 d on either a recommended control diet (7 % cFA, w/w) or a high-fat diet (20 % fatty acids, w/w). The high-fat diet was enriched with either cFA, trans fatty acid (tFA), a moderate proportion of saturated fatty acid (MSFA), or a high proportion of saturated fatty acid (HSFA). The most striking findings were observed in the gastrocnemius muscle with a HSFA diet. There was a significant increase in glucose-6-phosphate (306 %), glucose-1-phosphate (245 %), fructose-6-phosphate (400 %), fructose-1,6-bisphosphate (86 %), glyceraldehyde-3-phosphate (38 %), pyruvate (341 %), lactate (325 %), citrate (79 %) and the bisphosphorylated sugars as compared with the cFA diet. These changes were paralleled by an increase in muscle triacylglycerol content (49 %) and a decrease in glucose (39 %). In addition, the amount of cFA and the other types of fatty acid (i.e. tFA and MSFA) led to no great differences in glucose metabolism as compared with the respective control group. These data support the hypothesis that glucose changes induced by a HSFA diet are a multifaceted abnormality. Glucose and lactate transport and intracellular glucose metabolism could be the key biochemical defects involved in this detrimental effect on glucose metabolism.

Water-stable helical structure of tertiary amides of bicyclic β-amino acid bearing 7-azabicyclo[2.2.1]heptane. Full control of amide cis-trans equilibrium by bridgehead substitution.

PubMed

Hosoya, Masahiro; Otani, Yuko; Kawahata, Masatoshi; Yamaguchi, Kentaro; Ohwada, Tomohiko

2010-10-27

Helical structures of oligomers of non-natural β-amino acids are significantly stabilized by intramolecular hydrogen bonding between main-chain amide moieties in many cases, but the structures are generally susceptible to the environment; that is, helices may unfold in protic solvents such as water. For the generation of non-hydrogen-bonded ordered structures of amides (tertiary amides in most cases), control of cis-trans isomerization is crucial, even though there is only a small sterical difference with respect to cis and trans orientations. We have established methods for synthesis of conformationally constrained β-proline mimics, that is, bridgehead-substituted 7-azabicyclo[2.2.1]heptane-2-endo-carboxylic acids. Our crystallographic, 1D- and 2D-NMR, and CD spectroscopic studies in solution revealed that a bridgehead methoxymethyl substituent completely biased the cis-trans equilibrium to the cis-amide structure along the main chain, and helical structures based on the cis-amide linkage were generated independently of the number of residues, from the minimalist dimer through the tetramer, hexamer, and up to the octamer, and irrespective of the solvent (e.g., water, alcohol, halogenated solvents, and cyclohexane). Generality of the control of the amide equilibrium by bridgehead substitution was also examined.

Conjugated Fatty Acid Synthesis

PubMed Central

Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

2012-01-01

Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

Intake of butter naturally enriched with cis9,trans11 conjugated linoleic acid reduces systemic inflammatory mediators in healthy young adults.

PubMed

Penedo, Letícia A; Nunes, Juliana C; Gama, Marco Antônio S; Leite, Paulo Emilio C; Quirico-Santos, Thereza F; Torres, Alexandre G

2013-12-01

A conjugated linoleic acid (CLA) depletion-repletion study was carried out to investigate the effects of dietary c9,t11 CLA on C-reactive protein, transcription factor NFκB, metalloproteinases 2 and 9, inflammatory mediators (adiponectin, TNFα, IL-2, IL-4, IL-8, IL-10), body composition, and erythrocyte membrane composition in healthy normal-weight human adults. CLA depletion was achieved through an 8-week period of restricted dairy fat intake (depletion phase; CLA intake was 5.2±5.8 mg/day), followed by an 8-week period in which individuals consumed 20 g/day of butter naturally enriched with c9,t11 CLA (repletion phase; CLA intake of 1020±167 mg/day). The participants were 29 healthy adult volunteers (19 women and 10 men, aged 22 to 36 years), with body mass index between 18.0 and 29.9 kg m(-2). Blood samples were collected at baseline and at the end of both depletion and repletion phases. The content of CLA in erythrocytes decreased during CLA-depletion and increased during CLA-repletion. Intake of CLA-enriched butter increased the serum levels of anti-inflammatory IL-10 but reduced transcription factor NFκB in blood and serum levels of TNFα, IL-2, IL-8 and inactive metalloproteinase-9. Moreover, reduced activity of metalloproteinases 2 and 9 in serum was observed during the CLA-repletion period. In contrast, intake of CLA-enriched butter had no effects on body composition (DXA analysis) as well as on serum levels of adiponectin, C-reactive protein, and IL-4. Taken together, our results indicate that the intake of a c9,t11 CLA-enriched butter by normal-weight subjects induces beneficial changes in immune modulators associated with sub-clinical inflammation in overweight individuals. © 2013.

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

PubMed

Quazi, Faraz; Molday, Robert S

2014-04-01

The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.

Rat urinary metabolites of [9,10-methylene-14C] sterculic acid.

PubMed

Eisele, T A; Yoss, J K; Nixon, J E; PAwlowski, N E; Libbey, L M; Sinnhuber, R O

1977-07-20

1. The metabolism of [9,10-methylene-14C] sterculic acid was studied in corn oil and Stercula foetida oil fed rats. The majority of the radioactivity was excreted into the urine as short chain dicarboxylic acids. The main urinary metabolites were cis-3,4-methylene adipic acid, cis-3,4-methylene suberic acid, trans-3,4-methylene adipic acid, cis-3,4-methylene pimelic acid, and cis-3,4-methylene azelic acid. 2. Formation of these urinary metabolites requires alpha-, beta-, and omega-oxidation plus reduction of the cyclopropene ring to a cyclopropane ring. Sterculic acid must be transported through both mitochondrial and microsomal systems. 3. Other non-radioactive urinary compounds were also identified. A proposed pathway for the metabolism of sterculic acid and possible detrimental effects caused by these metabolites is discussed.

Thermodynamics of the clusterization process of cis isomers of unsaturated fatty acids at the air/water interface.

PubMed

Vysotsky, Yu B; Belyaeva, E A; Fainerman, V B; Vollhardt, D; Aksenenko, E V; Miller, R

2009-04-02

In the framework of the semiempirical PM3 method, the thermodynamic parameters of cis isomers of unsaturated carboxylic acids at the air/water interface are studied. The model systems used are unsaturated cis fatty acid of the composition Delta = 12-15 and omega = 6-11, where Delta and omega refer to the number of carbon atoms between the functional group and double bond, and that between the double bond and methyl group, respectively. For dimers, trimers, and tetramers of the four acid series, the thermodynamic parameters of clusterization are calculated. It is shown that the position of the double bond does not significantly affect the values of thermodynamic parameters of formation and clusterization of carboxylic acids for equal chain lengths (n = Delta + omega). The calculated results show that for cis unsaturated fatty acid with odd Delta values the spontaneous clusterization threshold corresponds to n = 17-18 carbon atoms in the alkyl chain, while for monounsaturated acids with even Delta values this threshold corresponds to n = 18-19 carbon atoms in the alkyl chain. These differences in the clusterization threshold between the acids with even and odd Delta values are attributed to the formation of additional intermolecular hydrogen bonds between the ketonic oxygen atom of one monomer and the hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with odd Delta values or between the hydroxyl oxygen atom of one monomer and hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with even Delta values. The results obtained in the study agree satisfactorily with our experimental data for cis unsaturated nervonic (Delta15, omega9) and erucic acids (Delta13, omega9), and published data for some fatty acids, namely cis-16-heptadecenoic (Delta16, omega1), cis-9-hexadecenoic (Delta7, omega9), cis-11-eicosenoic (Delta11, omega9) and cis-9-octadecenoic acid (Delta9, omega9).

The cis conformation of proline leads to weaker binding of a p53 peptide to MDM2 compared to trans.

PubMed

Zhan, Yingqian Ada; Ytreberg, F Marty

2015-06-01

The cis and trans conformations of the Xaa-Pro (Xaa: any amino acid) peptide bond are thermodynamically stable while other peptide bonds strongly prefer trans. The effect of proline cis-trans isomerization on protein binding has not been thoroughly investigated. In this study, computer simulations were used to calculate the absolute binding affinity for a p53 peptide (residues 17-29) to MDM2 for both cis and trans isomers of the p53 proline in position 27. Results show that the cis isomer of p53(17-29) binds more weakly to MDM2 than the trans isomer, and that this is primarily due to the difference in the free energy cost associated with the loss of conformational entropy of p53(17-29) when it binds to MDM2. The population of cis p53(17-29) was estimated to be 0.8% of the total population in the bound state. The stronger binding of trans p53(17-29) to MDM2 compared to cis may leave a minimal level of p53 available to respond to cellular stress. This study demonstrates that it is feasible to estimate the absolute binding affinity for an intrinsically disordered protein fragment binding to an ordered protein that are in good agreement with experimental results. Copyright © 2015 Elsevier Inc. All rights reserved.

Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis.

PubMed

Ashwell, Melissa S; Ceddia, Ryan P; House, Ralph L; Cassady, Joseph P; Eisen, Eugene J; Eling, Thomas E; Collins, Jennifer B; Grissom, Sherry F; Odle, Jack

2010-09-01

The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice. In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation; however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days. Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of .01, and 775 were considered significant using a false discovery rate (FDR) threshold of .05. While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4alpha, a transcription factor important in controlling liver metabolic status. Copyright 2010 Elsevier Inc. All rights reserved.

Glutathione S-transferases act as isomerases in isomerization of 13-cis-retinoic acid to all-trans-retinoic acid in vitro.

PubMed

Chen, H; Juchau, M R

1997-11-01

A discovery that rapid enzymic isomerization of 13-cis-retinoic acid (13-cRA) to all-trans-retinoic acid (t-RA) can be catalysed by purified hepatic glutathione S-transferases (GSTs; EC 2.5.1.18) from rat is now reported. Rates of cis-trans isomerization were determined quantitatively by HPLC. GST-catalysed reactions reached equilibrium rapidly, in marked contrast with uncatalysed or GSH-catalysed isomerizations. The GST-catalysed reaction exhibited substrate saturation kinetics with a Km of approx. 8 microM. The maximal velocity of the reaction and the catalytic efficiency of GSTs were determined. The initial rate of the reaction increased linearly as a function of enzyme concentration. Catalysis by GSTs was independent of the presence of GSH, indicating that GSTs act as GSH-independent isomerases as well as transferases. Incubation with guanidine (7-8 M) or heat-inactivation of GSTs (100 degrees C for 3 min) decreased isomerase activities by approx. 50% and 75% respectively. The same heat treatment did not significantly inhibit isomerization catalysed by GSH and apoferritin, indicating that the observed decrease in isomerase activity by heat inactivation was not primarily due to oxidation of protein thiol groups in the GSTs. The specific activity of GSTs was approx. 23- and 340-fold those of GSH and apoferritin respectively when comparisons were made on the basis of free thiol concentrations, indicating that free thiol in GSTs cannot account for the majority of observed isomerase activities and suggesting that specific conformations of GSTs are important for such activities. Complete inhibition of the reaction by low concentrations of N-ethylmaleimide (10 microM) demonstrated that intact protein thiols are required for the isomerase activities of GSTs.

Rapid, simultaneous and nanomolar determination of pyroglutamic acid and cis-/trans-urocanic acid in human stratum corneum by hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization tandem mass spectrometry.

PubMed

Joo, Kyung-Mi; Han, Ji Yeon; Son, Eui Dong; Nam, Gae-Won; Chung, Han Young; Jeong, Hye-Jin; Cho, Jun-Cheol; Lim, Kyung-Min

2012-05-15

A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to tandem mass spectrometric (HILIC-MS/MS) method for the simultaneous determination of pyroglutamic acid, cis- and trans-urocanic acid in human skin stratum corneum (SC) were developed and validated. This method was carried out without derivatization or addition of ion-pair additives in mobile phase. The analytes were extracted by PBS buffer solution and analyzed using an electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an AQUITY UPLC amide column using gradient elution with the mobile phase of water and acetonitrile. The standard curves were linear over the concentration range of 1.0-250 ng/mL with a correlation coefficient higher than 0.999 with an LLOQ of 0.5 ng/mL. The lower limits of detection (LLOD) of these analytes were lower than 0.2 ng/mL. The intra- and inter-day precisions were measured to be below 7.7% and accuracies were within the range of 94.3-102.6%. The validated method was successfully applied to determine the level of pyroglutamic acid and cis-/trans-urocanic acid in the SC samples from forearm and forehead region of 19 human volunteers. Copyright © 2012 Elsevier B.V. All rights reserved.

9-cis-Retinoic Acid Promotes Cell Adhesion Through Integrin Dependent and Independent Mechanisms Across Immune Lineages

PubMed Central

Whelan, Jarrett T.; Chen, Jianming; Miller, Jabin; Morrow, Rebekah L.; Lingo, Joshuah D.; Merrell, Kaitlin; Shaikh, Saame Raza; Bridges, Lance C.

2012-01-01

Retinoids are essential in the proper establishment and maintenance of immunity. Although retinoids are implicated in immune related processes, their role in immune cell adhesion has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) on human hematopoietic cell adhesion was investigated. 9-cis-RA treatment specifically induced cell adhesion of the human immune cell lines HuT-78, NB4, RPMI 8866, and U937. Due to the prominent role of integrin receptors in mediating immune cell adhesion, we sought to evaluate if cell adhesion was integrin-dependent. By employing a variety of integrin antagonist including function-blocking antibodies and EDTA, we establish that 9-cis-RA prompts immune cell adhesion through established integrin receptors in addition to a novel integrin-independent process. The novel integrin-independent adhesion required the presence of retinoid and was attenuated by treatment with synthetic corticosteroids. Finally, we demonstrate that 9-cis-RA treatment of primary murine B-cells induces ex vivo adhesion that persists in the absence of integrin function. Our study is the first to demonstrate that 9-cis-retinoic acid influences immune cell adhesion through at least two functionally distinct mechanisms. PMID:22925918

Conjugated linoleic acid and vaccenic acid in rumen, plasma, and milk of cows fed fish oil and fats differing in saturation of 18 carbon fatty acids.

PubMed

AbuGhazaleh, A A; Schingoethe, D J; Hippen, A R; Kalscheur, K F

2003-11-01

The objective of this study was to examine the effect of feeding fish oil (FO) along with fat sources that varied in saturation of 18 carbon fatty acids (high stearic, high oleic, high linoleic, or high linolenic acids) on rumen, plasma, and milk fatty acid profiles. Four primiparous Holstein cows at 85 d in milk (+/- 40) were assigned to 4 x 4 Latin squares with 4-wk periods. Treatment diets were 1) 1% FO plus 2% commercial fat high in stearic acid (HS); 2) 1% FO plus 2% fat from high oleic acid sunflower seeds (HO); 3) 1% FO plus 2% fat from high linoleic acid sunflower seeds (HLO); and 4) 1% FO plus 2% fat from flax seeds (high linolenic; HLN). Diets were formulated to contain 18% crude protein and were composed of 50% (dry basis) concentrate mix, 25% corn silage, 12.5% alfalfa silage, and 12.5% alfalfa hay. Milk production, milk protein percentages and yields, and dry matter intake were similar across diets. Milk fat concentrations and yields were least for HO and HLO diets. The proportion of milk cis-9, trans-11 conjugated linoleic acid (CLA; 0.71, 0.99, 1.71, and 1.12 g/100 g fatty acids, respectively), and vaccenic acid (TVA; 1.85, 2.60, 4.14, and 2.16 g/100 g fatty acids, respectively) were greatest with the HLO diet. The proportions of ruminal cis-9, trans-11 CLA (0.09, 0.16, 0.18, and 0.16 g/100 g fatty acids, respectively) were similar for the HO, HLO, and HLN diets and all were higher than for the HS diet. The proportions of TVA (2.85, 4.36, 8.69, and 4.64 g/100 g fatty acids, respectively) increased with the HO, HLO, and HLN diets compared with the HS diets, and the increase was greatest with the HLO diet. The effects of fat supplements on ruminal TVA concentrations were also reflected in plasma triglycerides, (2.75, 4.64, 8.77, and 5.42 g/100 g fatty acids, respectively); however, there were no differences in the proportion of cis-9, trans-11 CLA (0.06, 0.07, 0.06, and 0.07 g/100 g fatty acids, respectively). This study further supports the

Metabolism of 13-cis-retinoic acid by a rat liver 9000g supernatant preparation.

PubMed

Vane, F M; Buggé, C J; Williams, T H

1982-01-01

The in vitro metabolites formed on incubation of 13-cis-retinoic acid (13-cis-RA, isotretinoin) with a 9000g rat liver supernatant system were isolated by HPLC and identified by their mass and NMR spectra. The major metabolic pathway was hydroxylation at C4 to give 4-hydroxy-13-cis-RA, which was rapidly oxidized to 4-oxo-13-cis-RA, the major isolated metabolite. Further metabolism of this 4-oxo metabolite led to two novel compounds, 2-hydroxy-4-oxo-13-cis-RA and 3-hydroxy-4-oxo-13-cis-RA. In addition, small amounts of 13-cis-RA and 4-oxo-13-cis-RA were enzymatically converted to their all-trans isomers. Support for these pathways was obtained by the metabolism of reference samples of 4-hydroxy-13-cis-RA, 4-oxo-13-cis-RA, all-trans-RA, and 4-oxo-all-trans-RA. The predominant formation of 4-oxo metabolites of 13-cis-RA in this in vitro rat system and the results from previously reported in vivo metabolism studies suggest that oxidation at C4 is a major metabolic pathway of 13-cis-RA in both rats and humans.

Mapping cis- and trans-regulatory effects across multiple tissues in twins

PubMed Central

Grundberg, Elin; Small, Kerrin S.; Hedman, Åsa K.; Nica, Alexandra C.; Buil, Alfonso; Keildson, Sarah; Bell, Jordana T.; Yang, Tsun-Po; Meduri, Eshwar; Barrett, Amy; Nisbett, James; Sekowska, Magdalena; Wilk, Alicja; Shin, So-Youn; Glass, Daniel; Travers, Mary; Min, Josine L.; Ring, Sue; Ho, Karen; Thorleifsson, Gudmar; Kong, Augustine; Thorsteindottir, Unnur; Ainali, Chrysanthi; Dimas, Antigone S.; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lowe, Christopher E.; Di Meglio, Paola; Montgomery, Stephen B.; Parts, Leopold; Potter, Simon; Surdulescu, Gabriela; Tsaprouni, Loukia; Tsoka, Sophia; Bataille, Veronique; Durbin, Richard; Nestle, Frank O.; O’Rahilly, Stephen; Soranzo, Nicole; Lindgren, Cecilia M.; Zondervan, Krina T.; Ahmadi, Kourosh R.; Schadt, Eric E.; Stefansson, Kari; Smith, George Davey; McCarthy, Mark I.; Deloukas, Panos; Dermitzakis, Emmanouil T.; Spector, Tim D.

2013-01-01

Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many eQTL studies typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis-effect on expression cannot be accounted for by common cis-variants, a finding which exposes the contribution of low frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene and identify several replicating trans-variants which act predominantly in a tissue-restricted manner and may regulate the transcription of many genes. PMID:22941192

Teratogenicity of isotretinoin revisited: species variation and the role of all-trans-retinoic acid.

PubMed

Nau, H

2001-11-01

This paper reviews the teratogenicity of isotretinoin in regard to aspects of species variation, toxicokinetics, and metabolism. Particular emphasis is given to the hypothesis that most effects of isotretinoin (13-cis-retinoic acid) are mediated by isomerization to the all-trans-retinoic acid. This mechanism of action would provide a basis for the understanding of species differences and the extrapolation of experimental results to the human situation and thus improve drug development. The insensitive species (rat, mouse) eliminate the drug rapidly through detoxification to the beta-glucuronide; also, placental transfer is limited in these species. On the other hand, in sensitive species (primates), the drug is predominantly metabolized to the active 13-cis-4-oxo-retinoic acid; placental transfer is more extensive here. The beta-glucuronides showed limited placental transfer in all species examined; these metabolites exhibited very low, if any, measurable concentrations in the human. The 13-cis-retinoic acid is not appreciably bound to cellular retinoid-binding proteins or nuclear receptors and exhibits low tissue distribution and placental transfer. Its access to the nucleus may be extensive. Because of the long half life of 13-cis-retinoic acid, continuous isomerization results in significant area under the concentration-time curve levels of all-trans-retinoic acid in the mouse, monkey and the human; the all-trans-retinoic acid formed is extensively distributed across the placenta and may be an important factor that contributes to the teratogenic potency of 13-cis-retinoic acid. Isomerization cannot explain the teratogenic effects of 13-cis-retinoic acid in the rat and rabbit. It is concluded that the high teratogenic activity of isotretinoin in sensitive species (human, monkey) is related to slow elimination of the 13-cis-isomer, to metabolism to the 4-oxo-derivative, to increased placental transfer, to continuous isomerization and significant exposure of the

Changes in dietary intake and food sources of saturated and cis and trans unsaturated fatty acids in Costa Rican adolescents: 1996 versus 2006.

PubMed

Monge-Rojas, Rafael; Aragón, M Catalina; Chinnock, Anne; Campos, Hannia; Colón-Ramos, Uriyoán

2013-04-01

To identify how dietary intake and food sources of saturated (SFA) and cis (PUFA) and trans (TFA) unsaturated fatty acids in the diet of Costa Rican adolescents changed from 1996 to 2006--a period with several public health nutrition changes. Cross-sectional comparisons used data from measured food records of 133 adolescents (ages 12-17 y) surveyed in 1996 and a similar group of adolescents surveyed in 2006. Values obtained in 1996 and 2006 were compared with the current World Health Organization guidelines for chronic disease prevention. Adolescents surveyed in 2006 reported a significantly higher mean daily energy intake from linoleic acid (LA) and alpha-linolenic acid (ALA) (0.9% and 7.8%, respectively) compared with the 1996 cohort, whereas SFA and TFA were significantly lower (9.5% and 1.3%, respectively). Food sources of fat also changed. In 2006, 2% of SFA in the diet came from palm shortening (compared with 34% in 1996); 39% of TFA came from ruminant-derived foods (in 1996, soybean oil was the main contributor of TFA, 34%), and bakery products (mainly pre-packaged cookies) provided 25% of the source of TFA, compared with only 11% in 1996. Dietary fatty intake of Costa Rican adolescents in 2006 is closer to WHO guidelines compared with 1996. After public health initiatives that changed fatty acid profile of most foods, intakes of TFA, SFA, and food sources of fatty acids in adolescents' diets improved. Public health nutrition efforts should continue to strengthen diets that are low in SFA and TFA and higher in ALA content among Costa Rican adolescents. Copyright © 2013 Elsevier Inc. All rights reserved.

Biohydrogenation of C20 polyunsaturated fatty acids by anaerobic bacteria.

PubMed

Sakurama, Haruko; Kishino, Shigenobu; Mihara, Kousuke; Ando, Akinori; Kita, Keiko; Takahashi, Satomi; Shimizu, Sakayu; Ogawa, Jun

2014-09-01

The PUFAs include many bioactive lipids. The microbial metabolism of C18 PUFAs is known to produce their bioactive isomers, such as conjugated FAs and hydroxy FAs, but there is little information on that of C20 PUFAs. In this study, we aimed to obtain anaerobic bacteria with the ability to produce novel PUFAs from C20 PUFAs. Through the screening of ∼100 strains of anaerobic bacteria, Clostridium bifermentans JCM 1386 was selected as a strain with the ability to saturate PUFAs during anaerobic cultivation. This strain converted arachidonic acid (cis-5,cis-8,cis-11,cis-14-eicosatetraenoic acid) and EPA (cis-5,cis-8,cis-11,cis-14,cis-17-EPA) into cis-5,cis-8,trans-13-eicosatrienoic acid and cis-5,cis-8,trans-13,cis-17-eicosatetraenoic acid, giving yields of 57% and 67% against the added PUFAs, respectively. This is the first report of the isolation of a bacterium transforming C20 PUFAs into corresponding non-methylene-interrupted FAs. We further investigated the substrate specificity of the biohydrogenation by this strain and revealed that it can convert two cis double bonds at the ω6 and ω9 positions in various C18 and C20 PUFAs into a trans double bond at the ω7 position. This study should serve to open up the development of novel potentially bioactive PUFAs. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Glutathione S-transferases act as isomerases in isomerization of 13-cis-retinoic acid to all-trans-retinoic acid in vitro.

PubMed Central

Chen, H; Juchau, M R

1997-01-01

A discovery that rapid enzymic isomerization of 13-cis-retinoic acid (13-cRA) to all-trans-retinoic acid (t-RA) can be catalysed by purified hepatic glutathione S-transferases (GSTs; EC 2.5.1.18) from rat is now reported. Rates of cis-trans isomerization were determined quantitatively by HPLC. GST-catalysed reactions reached equilibrium rapidly, in marked contrast with uncatalysed or GSH-catalysed isomerizations. The GST-catalysed reaction exhibited substrate saturation kinetics with a Km of approx. 8 microM. The maximal velocity of the reaction and the catalytic efficiency of GSTs were determined. The initial rate of the reaction increased linearly as a function of enzyme concentration. Catalysis by GSTs was independent of the presence of GSH, indicating that GSTs act as GSH-independent isomerases as well as transferases. Incubation with guanidine (7-8 M) or heat-inactivation of GSTs (100 degrees C for 3 min) decreased isomerase activities by approx. 50% and 75% respectively. The same heat treatment did not significantly inhibit isomerization catalysed by GSH and apoferritin, indicating that the observed decrease in isomerase activity by heat inactivation was not primarily due to oxidation of protein thiol groups in the GSTs. The specific activity of GSTs was approx. 23- and 340-fold those of GSH and apoferritin respectively when comparisons were made on the basis of free thiol concentrations, indicating that free thiol in GSTs cannot account for the majority of observed isomerase activities and suggesting that specific conformations of GSTs are important for such activities. Complete inhibition of the reaction by low concentrations of N-ethylmaleimide (10 microM) demonstrated that intact protein thiols are required for the isomerase activities of GSTs. PMID:9581548

Hazard identification of cis/trans-zearalenone through the looking-glass.

PubMed

Dellafiora, Luca; Galaverna, Gianni; Dall'Asta, Chiara; Cozzini, Pietro

2015-12-01

Among the food-related health issues, the presence of contaminants has a prominent role, due to the wide range of exogenous compounds that can occur in food commodities and to their large differences in structure and biological activity. A comprehensive assessment of the related risk is thus actually demanding in terms of time and facilities involved. In this context, the use of computational strategies can be an effective choice for supporting the hazard identification procedure at the early stage. In this work, we focused on the food contaminant zearalenone by comparing the trans and cis isomers, respectively the well-known mycoestrogen and its still largely understudied isomer. We estimated the possible effects exerted by human metabolism on the xenoestrogenicity of cis-ZEN by using a validated in silico strategy based on docking simulations and rescoring procedures. Similarly, the exploitation of the most promising enzymatic detoxifying routes designed for trans-ZEN - which relies on the enzyme lactono hydrolase from Clonostachys rosea - has been assessed for the cis-isomer as well. Our results showed that both isomers can act as functional analogues with respect to xenoestrogenic activity, and several cis-ZEN metabolites with high biological potential have been identified. On the contrary, in spite of the high degree of structural analogy, the cis isomer showed a pattern of interaction with the degrading enzyme in stark contrast with that observed for trans-ZEN. For these reasons, the outcomes presented herein strongly support the inclusion of cis-ZEN in further studies of occurrence, metabolism and bioactivity assessment, and suggest the need for a dedicated handling for the cis isomer in risk assessment studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tung tree (Vernicia fordii, Hemsl.) genome and transcriptome sequencing reveals coordinate upregulation of fatty acid beta-oxidation and triacylglycerol biosynthesis pathways during eleostearic acid accumulation in seeds

USDA-ARS?s Scientific Manuscript database

The tung tree (Vernicia fordii) is one of only a few plant species that produces high oil-yielding seeds rich in a-eleostearic acid (a-ESA, 18:3'9cis,11trans,13trans), a conjugated trienoic fatty acid with valuable industrial and medical properties. Previous attempts have been made to engineer tung...

Both the cis-trans equilibrium and isomerization dynamics of a single proline amide modulate β2-microglobulin amyloid assembly

PubMed Central

Torbeev, Vladimir Yu.; Hilvert, Donald

2013-01-01

The human protein β2-microglobulin (β2m) aggregates as amyloid fibrils in patients undergoing long-term hemodialysis. Isomerization of Pro32 from its native cis to a nonnative trans conformation is thought to trigger β2m misfolding and subsequent amyloid assembly. To examine this hypothesis, we systematically varied the free-energy profile of proline cis-trans isomerization by replacing Pro32 with a series of 4-fluoroprolines via total chemical synthesis. We show that β2m’s stability, (un)folding, and aggregation properties are all influenced by the rate and equilibrium of Pro32 cis-trans isomerization. As anticipated, the β2m monomer was either stabilized or destabilized by respective incorporation of (2S,4S)-fluoroproline, which favors the native cis amide bond, or the stereoisomeric (2S,4R)-fluoroproline, which disfavors this conformation. However, substitution of Pro32 with 4,4-difluoroproline, which has nearly the same cis-trans preference as proline but an enhanced isomerization rate, caused pronounced destabilization of the protein and increased oligomerization at neutral pH. More remarkably, these subtle alterations in chemical composition—incorporation of one or two fluorine atoms into a single proline residue in the 99 amino acid long protein—modulated the aggregation properties of β2m, inducing the formation of polymorphically distinct amyloid fibrils. These results highlight the importance of conformational dynamics for molecular assembly of an amyloid cross-β structure and provide insights into mechanistic aspects of Pro32 cis-trans isomerism in β2m aggregation. PMID:24262149

Both the cis-trans equilibrium and isomerization dynamics of a single proline amide modulate β2-microglobulin amyloid assembly.

PubMed

Torbeev, Vladimir Yu; Hilvert, Donald

2013-12-10

The human protein β2-microglobulin (β2m) aggregates as amyloid fibrils in patients undergoing long-term hemodialysis. Isomerization of Pro32 from its native cis to a nonnative trans conformation is thought to trigger β2m misfolding and subsequent amyloid assembly. To examine this hypothesis, we systematically varied the free-energy profile of proline cis-trans isomerization by replacing Pro32 with a series of 4-fluoroprolines via total chemical synthesis. We show that β2m's stability, (un)folding, and aggregation properties are all influenced by the rate and equilibrium of Pro32 cis-trans isomerization. As anticipated, the β2m monomer was either stabilized or destabilized by respective incorporation of (2S,4S)-fluoroproline, which favors the native cis amide bond, or the stereoisomeric (2S,4R)-fluoroproline, which disfavors this conformation. However, substitution of Pro32 with 4,4-difluoroproline, which has nearly the same cis-trans preference as proline but an enhanced isomerization rate, caused pronounced destabilization of the protein and increased oligomerization at neutral pH. More remarkably, these subtle alterations in chemical composition--incorporation of one or two fluorine atoms into a single proline residue in the 99 amino acid long protein--modulated the aggregation properties of β2m, inducing the formation of polymorphically distinct amyloid fibrils. These results highlight the importance of conformational dynamics for molecular assembly of an amyloid cross-β structure and provide insights into mechanistic aspects of Pro32 cis-trans isomerism in β2m aggregation.

Synthesis, spectroscopic and TD-DFT quantum mechanical study of azo-azomethine dyes. A laser induced trans-cis-trans photoisomerization cycle

NASA Astrophysics Data System (ADS)

Georgiev, Anton; Kostadinov, Anton; Ivanov, Deyan; Dimov, Deyan; Stoyanov, Simeon; Nedelchev, Lian; Nazarova, Dimana; Yancheva, Denitsa

2018-03-01

This paper describes the synthesis, spectroscopic characterization and quantum mechanical calculations of three azo-azomethine dyes. The dyes were synthesized via condensation reaction between 4-(dimethylamino)benzaldehyde and three different 4-aminobenzene azo dyes. Quantum chemical calculations on the optimized molecular geometry and electron densities of the trans (E) and cis (Z) isomers and their vibrational frequencies have been computed by using DFT/B3LYP density-functional theory with 6-311 ++G(d,p) basis set in vacuo. The thermodynamic parameters such as total electronic energy E (RB3LYP), enthalpy H298 (sum of electronic and thermal enthalpies), free Gibbs energy G298 (sum of electronic and thermal free Gibbs energies) and dipole moment μ were computed for trans (E) and cis (Z) isomers in order to estimate the ΔEtrans → cis, Δμtrans → cis,ΔHtrans → cis, ΔGtrans → cis and ΔStrans → cis values. After molecular geometry optimization the electronic spectra have been obtained by TD-DFT calculations at same basis set and correlated with the spectra of vapour deposited nanosized films of the dyes. The NBO analysis was performed in order to understand the intramolecular charge transfer and energy of resonance stabilization. Solvatochromism was investigated by UV-VIS spectroscopy in five different organic solvents with increasing polarity. The dynamic photoisomerization experiments have been performed in DMF by pump lasers λ = 355 nm (mostly E → Z) and λ = 491 nm (mostly Z → E) in spectral region 300 nm - 800 nm at equal concentrations and times of illumination in order to investigate the photodynamical trans-cis-trans properties of the sbnd CHdbnd Nsbnd and sbnd Ndbnd Nsbnd chromophore groups of the dyes.

Ring[bond]chain tautomerism of 2-Aryl-substituted cis- and trans-decahydroquinazolines.

PubMed

Lázár, László; Göblyös, Anikó; Martinek, Tamás A; Fülöp, Ferenc

2002-07-12

In CDCl(3) at 300 K, 2-aryl-substituted cis- and trans-3-isopropyldecahydroquinazolines and trans-3-phenyldecahydroquinazolines proved to be three-component (r(1)[bond]o[bond]r(2)) ring[bond]chain tautomeric mixtures, whereas only ring-closed tautomers could be detected for the 3-methyl-substituted analogues. The proportions of the ring-chain tautomeric forms at equilibrium were strongly influenced by the N-substitutents and the cis-trans ring junction and could be described by the equation log K(X) = rho sigma(+) + log K(X=H). These are the first examples among 2-aryl-1,3-N,N-heterocycles of a three-component ring-chain tautomeric equilibrium characterized by a Hammett-type equation. The stabilities of the ring-closed forms of cis- and trans-2-aryldecahydroquinazolines and the corresponding 3,1-benzoxazines were found to increase in the following sequence of the heteroatom at position 3: NPh < N-i-Pr < O < NMe.

Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

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

Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki

2013-03-29

Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. Themore » complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner.« less

Synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans.

PubMed

Munshi, K L; Dikshit, D K; Kapil, R S; Anand, N

1974-04-01

The synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans was undertaken because these compounds incorportae the essential structural features of certain 2,3-diphenyl-benzofurans and 1,2,3-triphenylalkanones reported earlier to have marked antifertility activity. The synthesis of the 2 tetrahydrofurans was achieved by the cyclization of corresponding 2,3,4-triphenylbutane-1,4-diols upon heating with dimethyl sulfoxide (DMSO). The butane 1,4-diols were in turn prepared either by direct litium aluminum hydride (LAH) reduction of methyl 3-benzoyl-2,3-diphenylpropionates or by conversion of these propionates to delta-3,4-butryrolactones followed by LAH reduction. The propionates were prepared from the Fiedel-Crafts reaction of 2,3-diphenylsuccinic anhydride with benzene. Tetrahydrofurans were tested for their antiimplantation activity in rats. 2,3-trans-3,4-cis-2,4-diphenyl-3-p -(beta-pyrrolidinoethoxy) phenyltetrahydrofuran oxalate was found to inhibit implantation completely at 50 mg/kg, but was inefective at a lower dose.

Comparison of alternative beef production systems based on forage finishing or grain-forage diets with or without growth promotants: 2. Meat quality, fatty acid composition, and overall palatability.

PubMed

Faucitano, L; Chouinard, P Y; Fortin, J; Mandell, I B; Lafrenière, C; Girard, C L; Berthiaume, R

2008-07-01

Five beef cattle management regimens were evaluated for their effect on meat quality, fatty acid composition, and overall palatability of the longis-simus dorsi (LD) muscle in Angus cross steers. A 98-d growing phase was conducted using grass silage with or without supplementation of growth promotants (Revalor G and Rumensin) or soybean meal. Dietary treatments in the finishing phase were developed with or without supplementation of growth promotants based on exclusive feeding of forages with no grain supplementation, or the feeding of grain:forage (70:30) diets. Growth promotants increased (P < 0.01) shear force and tended (P = 0.06) to increase toughness of the LD muscle due to limited postmortem proteolytic activity (lower myofibrillar fragmentation index value; P = 0.02). Grain feeding increased DM and intramuscular fat content (P = 0.03 and P = 0.05, respectively) in the LD but decreased the sensory panel tenderness score (P = 0.01). Growth promotants increased (P trans isomers of C18:1, and cis-9, trans-11 C18:2. Exclusive feeding of forages increased the proportion of cis-9, cis-12, cis-15 C18:3 as well as several other isomers of the n-3 family and decreased in the ratio of n-6 to n-3 fatty acids in the LD muscle as compared with supplementing grain (P < 0.05). In addition, the forage-based diet increased (P < 0.01) the concentration in the intramuscular fat of several intermediates (cis-9, trans-11, cis-15 C18:3; trans-11, cis-15 C18:2; trans-11 C18:1) of ruminal biohydrogenation. Forage feeding also increased the proportion of cis-9, trans-11 C18:2 (P < 0.01) and decreased the concentration of trans-10 C18:1 in the LD muscle (P = 0.03). It is concluded that quality demands of health-conscious consumers can be met through a forage-finishing and growth promotants-free beef production system.

9-cis-retinoic acid represses estrogen-induced expression of the very low density apolipoprotein II gene.

PubMed

Schippers, I J; Kloppenburg, M; Snippe, L; Ab, G

1994-11-01

The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concentrated on a potential RXR recognition site, which deviates at only one position from a perfect direct A/GGGTCA repeat spaced by one nucleotide (DR-1) and was earlier identified as a common HNF-4/COUP-TF recognition site. However, band shift analysis revealed that this imperfect DR-1 motif does not interact with RXR alpha-homodimers. In accordance with this observation we found that this regulatory element does not mediate transactivation through RXR alpha in the presence of 9-cis-RA. However, our experiments revealed another, unexpected, effect of 9-cis-RA. Instead of stimulating, 9-cis-RA attenuated estrogen-induced expression of transfected estrogen-responsive VLDL-CAT reporter plasmids. This repression appeared to take place through the main estrogen response element (ERE) of the gene. Importantly, 9-cis-RA also strongly repressed the estrogen-induced expression of the endogenous apoVLDLII gene in cultured chicken hepatoma cells.

Mechanistic Studies on the Cis to Trans Epimerization of Trisubstituted-1,2,3,4-Tetrahydro-β-Carbolines

PubMed Central

Van Linn, Michael L.; Cook, James M.

2010-01-01

It is well known that Nb-benzyl tryptophan alkyl esters undergo the Pictet-Spengler reaction with aldehydes to furnish both cis and trans 1,2,3,4-tetrahydro-β-carbolines, with the trans isomer predominating. Epimerization at C-1 took place under acidic conditions to produce, exclusively, the thermodynamically more stable trans diastereomer via internal asymmetric induction. Recent kinetic experiments provided insight into the cis to trans epimerization mechanism involved in the Pictet-Spengler reaction of 1,2,3-trisubsituted tetrahydro-β-carbolines. Since the epimerization reaction had been shown to be sensitive to electronic effects at C-1, the rate data for a series of 1-phenyl-substituted-1,2,3,4-tetrahydro-β-carbolines was investigated via a Hammett study. Analysis of the data supported the presence of a positively charged intermediate with a ρ value of −1.4, although the existence of an iminium ion intermediate or a carbocationic intermediate could not be determined from this data alone. Analysis of the rate of epimerization demonstrated first-order kinetics with respect to TFA following the initial protonation of the substrate. This observation was consistent with the formation of a doubly protonated intermediate as the rate determining step in the carbocation-mediated cis to trans epimerization process. In addition, the observed first-order rate dependence was inconsistent with the retro Pictet-Spengler mechanism since protonation at the indole-2 position was not rate determining as demonstrated by kinetic isotope effects. Based on this kinetic data, the retro Pictet-Spengler pathway was ruled out for the cis to trans epimerization of 1,2,3-trisubstituted-1,2,3,4-tetrahydro-β-carbolines, while the olefinic mechanism had been ruled out by experiments carried out in TFA-d. PMID:20429580

9-Cis-Retinoic Acid Induces Growth Inhibition in Retinoid-Sensitive Breast Cancer and Sea Urchin Embryonic Cells via Retinoid X Receptor α and Replication Factor C3

PubMed Central

Maeng, Sejung; Kim, Gil Jung; Choi, Eun Ju; Yang, Hyun Ok; Lee, Dong-Sup

2012-01-01

There is widespread interest in defining factors and mechanisms that suppress the proliferation of cancer cells. Retinoic acid (RA) is a potent suppressor of mammary cancer and developmental embryonic cell proliferation. However, the molecular mechanisms by which 9-cis-RA signaling induces growth inhibition in RA-sensitive breast cancer and embryonic cells are not apparent. Here, we provide evidence that the inhibitory effect of 9-cis-RA on cell proliferation depends on 9-cis-RA-dependent interaction of retinoid X receptor α (RXRα) with replication factor C3 (RFC3), which is a subunit of the RFC heteropentamer that opens and closes the circular proliferating cell nuclear antigen (PCNA) clamp on DNA. An RFC3 ortholog in a sea urchin cDNA library was isolated by using the ligand-binding domain of RXRα as bait in a yeast two-hybrid screening. The interaction of RFC3 with RXRα depends on 9-cis-RA and bexarotene, but not on all-trans-RA or an RA receptor (RAR)-selective ligand. Truncation and mutagenesis experiments demonstrated that the C-terminal LXXLL motifs in both human and sea urchin RFC3 are critical for the interaction with RXRα. The transient interaction between 9-cis-RA-activated RXRα and RFC3 resulted in reconfiguration of the PCNA-RFC complex. Furthermore, we found that knockdown of RXRα or overexpression of RFC3 impairs the ability of 9-cis-RA to inhibit proliferation of MCF-7 breast cancer cells and sea urchin embryogenesis. Our results indicate that 9-cis-RA-activated RXRα suppresses the growth of RA-sensitive breast cancer and embryonic cells through RFC3. PMID:22949521

Proline cis-trans isomerization in staphylococcal nuclease: multi-substrate free energy perturbation calculations.

PubMed Central

Hodel, A.; Rice, L. M.; Simonson, T.; Fox, R. O.; Brünger, A. T.

1995-01-01

Staphylococcal nuclease A exists in two folded forms that differ in the isomerization state of the Lys 116-Pro 117 peptide bond. The dominant form (90% occupancy) adopts a cis peptide bond, which is observed in the crystal structure. NMR studies show that the relatively small difference in free energy between the cis and trans forms (delta Gcis-->trans approximately 1.2 kcal/mol) results from large and nearly compensating differences in enthalpy and entropy (delta Hcis-->trans approximately delta TScis-->trans approximately 10 kcal/mol). There is evidence from X-ray crystal structures that the structural differences between the cis and the trans forms of nuclease are confined to the conformation of residues 112-117, a solvated protein loop. Here, we obtain a thermodynamic and structural description of the conformational equilibrium of this protein loop through an exhaustive conformational search that identified several substates followed by free energy simulations between the substrates. By partitioning the search into conformational substates, we overcame the multiple minima problem in this particular case and obtained precise and reproducible free energy values. The protein and water environment was implicitly modeled by appropriately chosen nonbonded terms between the explicitly treated loop and the rest of the protein. These simulations correctly predicted a small free energy difference between the cis and trans forms composed of larger, compensating differences in enthalpy and entropy. The structural predictions of these simulations were qualitatively consistent with known X-ray structures of nuclease variants and yield a model of the unknown minor trans conformation. PMID:7613463

Biosynthesis of adipic acid via microaerobic hydrogenation of cis,cis-muconic acid by oxygen-sensitive enoate reductase.

PubMed

Sun, Jing; Raza, Muslim; Sun, Xinxiao; Yuan, Qipeng

2018-06-06

Adipic acid (AA) is an important dicarboxylic acid used for the manufacture of nylon and polyurethane plastics. In this study, a novel adipic acid biosynthetic pathway was designed by extending the cis,cis-muconic acid (MA) biosynthesis through biohydrogenation. Enoate reductase from Clostridium acetobutylicum (CaER), an oxygen-sensitive reductase, was demonstrated to have in vivo enzyme activity of converting cis,cis-muconic acid to adipic acid under microaerobic condition. Engineered Escherichia coli strains were constructed to express the whole pathway and accumulated 5.8 ± 0.9 mg/L adipic acid from simple carbon sources. Considering the different oxygen demands between cis,cis-muconic acid biosynthesis and its degradation, a co-culture system was constructed. To improve production, T7 promoter instead of lac promoter was used for higher level expression of the key enzyme CaER and the titer of adipic acid increased to 18.3 ± 0.6 mg/L. To decrease the oxygen supply to downstream strains expressing CaER, Vitreoscilla hemoglobin (VHb) was introduced to upstream strains for its ability on oxygen obtaining. This attempt further improved the production of this novel pathway and 27.6 ± 1.3 mg/L adipic acid was accumulated under microaerobic condition. Copyright © 2018. Published by Elsevier B.V.

Simultaneous determination of all-trans and 13-cis retinoic acids and their 4-oxo metabolites by adsorption liquid chromatography after solid-phase extraction.

PubMed

Lefebvre, P; Agadir, A; Cornic, M; Gourmel, B; Hue, B; Dreux, C; Degos, L; Chomienne, C

1995-04-07

All-trans retinoic acid (all-trans RA), the active metabolite of vitamin A, has been demonstrated to be an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (APL), the AML3 subtype of the FAB cytological classification. Complete remission is obtained by inducing terminal granulocytic differentiation of the leukemic cells. To study all-trans RA pharmacokinetics in patients with APL, a rapid, precise and selective high-performance liquid chromatographic (HPLC) assay was developed. This method is easy and shows good repeatability (C.V. = 8.41-12.44%), reproducibility (C.V. = 9.19-14.73%), accuracy (C.V. = 3.5-11%) and sensitivity with a detection limit of 5 pmol/ml. The analysis is performed using normal-phase HPLC in an isocratic mode with UV detection after solid-phase extraction on octadecyl (C18) columns. The mobile phase is hexane-dichloromethane-dioxane (78:18:4, v/v) containing 1% acetic acid.

trans- cis Isomerism and acylimine formation in DsRed chromophore models: Intrinsic rotation barriers

NASA Astrophysics Data System (ADS)

Olsen, Seth; Smith, Sean C.

2006-07-01

The chromophore of the red fluorescent protein DsRed contains an acylimine substituent to a GFP-like chromophore structure. The acylimine is formed from the trans peptide linkage between residues F65 and Q66 in immature DsRed, but has a cis configuration in the mature protein. The relationship between acylimine formation and trans- cis isomerization is unresolved. We have calculated bond rotation profiles for models of mature and immature DsRed chromophores using B3LYP DFT. The isomerization barrier is substantially reduced in acylimine-substituted models, providing prima facie evidence that acylimine formation precedes trans- cis isomerization in DsRed chromophores.

Cis- and trans-perfluorodecalin: Infrared spectra, radiative efficiency and global warming potential

NASA Astrophysics Data System (ADS)

Le Bris, Karine; DeZeeuw, Jasmine; Godin, Paul J.; Strong, Kimberly

2017-12-01

Perfluorodecalin (PFD) is a molecule used in various medical applications for its capacity to dissolve gases. This potent greenhouse gas was detected for the first time in the atmosphere in 2005. We present infrared absorption cross-section spectra of a pure vapour of cis- and trans-perfluorodecalin at a resolution of 0.1 cm-1. Measurements were performed in the 560-3000 cm-1 spectral range using Fourier transform spectroscopy. The spectra have been compared with previous experimental data and theoretical calculations by density functional theory. The new experimental absorption cross-sections have been used to calculate a lifetime-corrected radiative efficiency at 300 K of 0.62 W m-2 ppb-1 and 0.57 W.m-2.ppb-1 for the cis and trans isomers respectively. This leads to a 100-year time horizon global warming potential of 8030 for cis-PFD and 7440 for trans-PFD.

9-cis-retinoic acid increases apolipoprotein AI secretion and mRNA expression in HepG2 cells.

PubMed

Haghpassand, M; Moberly, J B

1995-10-01

HepG2 cells were studied as a model for regulation of hepatic apolipoprotein AI (apo AI) secretion and gene expression by 9-cis-retinoic acid. HepG2 cells cultured on plastic dishes were exposed to 9-cis-retinoic acid (9-cis-RA) for 48 h with a complete media change at 24 h. Apo AI mass in cultured media was determined by ELISA, by quantitative immunoblotting and by steady-state 35S-methionine labeling. Messenger RNA levels were determined by RNase protection using probes for apo AI and the housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (G3PDH). 9-cis-RA increased secretion of apo AI by 52% at doses of 10 and 1 microM (6.3 +/- 0.6 vs. 4.2 +/- 0.3; P < 0.005; 6.1 +/- 0.3 vs. 4.0 +/- 0.7 ng of apo AI/mg cell protein, P < 0.05) and by 35% at 0.1 microM (5.5 +/- 0.6 vs. 4.1 +/- 0.4 ng apo AI/mg protein, P < 0.05, n = 4). Immunoblotting results were consistent with results from ELISA (70% increase at 10 microM 9-cis-RA, P < 0.001; 34% increase at 1 microM, P < 0.005, n = 3). Metabolically labeled apoAI in the medium was increased by 39% following steady-state labeling in the presence of 10 microM 9-cis-RA (597 +/- 7 vs. 430 +/- 13 DPM/microliters media; P < 0.001; n = 4). 9-cis-RA (10 microM) also increased HepG2 cell apo AI mRNA expression by 76% (68 700 +/- 400 vs. 38 900 +/- 2700 DPM, P < 0.01, n = 4), whereas expression of G3PDH mRNA was slightly decreased (14%, P < 0.05). Thus, 9-cis-RA stimulates apo AI expression in HepG2 cells, suggesting a role for retinoids in activating endogenous apo AI gene expression.

Measurement of conjugated linoleic acid (CLA) in CLA-rich soy oil by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR).

PubMed

Kadamne, Jeta V; Jain, Vishal P; Saleh, Mohammed; Proctor, Andrew

2009-11-25

Conjugated linoleic acid (CLA) isomers in oils are currently measured as fatty acid methyl esters by a gas chromatography-flame ionization detector (GC-FID) technique, which requires approximately 2 h to complete the analysis. Hence, we aim to develop a method to rapidly determine CLA isomers in CLA-rich soy oil. Soy oil with 0.38-25.11% total CLA was obtained by photo-isomerization of 96 soy oil samples for 24 h. A sample was withdrawn at 30 min intervals with repeated processing using a second batch of oil. Six replicates of GC-FID fatty acid analysis were conducted for each oil sample. The oil samples were scanned using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the spectrum was collected. Calibration models were developed using partial least-squares (PLS-1) regression using Unscrambler software. Models were validated using a full cross-validation technique and tested using samples that were not included in the calibration sample set. Measured and predicted total CLA, trans,trans CLA isomers, total mono trans CLA isomers, trans-10,cis-12 CLA, trans-9,cis-11 CLA and cis-10,trans-12 CLA, and cis-9,trans-11 CLA had cross-validated coefficients of determinations (R2v) of 0.97, 0.98, 0.97, 0.98, 0.97, and 0.99 and corresponding root-mean-square error of validation (RMSEV) of 1.14, 0.69, 0.27, 0.07, 0.14, and 0.07% CLA, respectively. The ATR-FTIR technique is a rapid and less expensive method for determining CLA isomers in linoleic acid photo-isomerized soy oil than GC-FID.

New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the genotoxic effects of trans- and cis-EHMC.

PubMed

Nečasová, Anežka; Bányiová, Katarína; Literák, Jaromír; Čupr, Pavel

2017-02-01

Ethylhexyl methoxycinnamate (EHMC) is a widely used UV filter present in a large number of personal care products (PCPs). Under normal conditions, EHMC occurs in a mixture of two isomers: trans-EHMC and cis-EHMC in a ratio of 99:1. When exposed to sunlight, the trans isomer is transformed to the less stable cis isomer and the efficiency of the UV filter is reduced. To date, the toxicological effects of the cis-EHMC isomer remain largely unknown. We developed a completely new method for preparing cis-EHMC. An EHMC technical mixture was irradiated using a UV lamp and 98% pure cis-EHMC was isolated from the irradiated solution using column chromatography. The genotoxic effects of the isolated cis-EHMC isomer and the nonirradiated trans-EHMC were subsequently measured using two bioassays (SOS chromotest and UmuC test). In the case of trans-EHMC, significant genotoxicity was observed using both bioassays at the highest concentrations (0.5 - 4 mg mL -1 ). In the case of cis-EHMC, significant genotoxicity was only detected using the UmuC test at concentrations of 0.25 - 1 mg mL -1 . Based on these results, the NOEC was calculated for both cis- and trans-EHMC, 0.038 and 0.064 mg mL -1 , respectively. Risk assessment of dermal, oral and inhalation exposure to PCPs containing EHMC was carried out for a female population using probabilistic simulation and by using Quantitative in vitro to in vivo extrapolation (QIVIVE). The risk of cis-EHMC was found to be ∼1.7 times greater than trans-EHMC. In the case of cis-EHMC, a hazard index of 1 was exceeded in the 92nd percentile. Based on the observed differences between the isomers, EHMC application in PCPs requires detailed reassessment. Further exploration of the toxicological effects and properties of cis-EHMC is needed in order to correctly predict risks posed to humans and the environment. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 569-580, 2017. © 2016 Wiley Periodicals, Inc.

Synthesis and bacterial metabolism of cis- and trans-2-alkyl analogues of sodium cyclamate.

PubMed

Wiley, R A; Pearson, D A; Schmidt, V; Wesche, S B; Roxon, J J

1983-07-01

Sodium cyclamate is an effective artificial sweetner, which has been banned from the U.SD. market because of alleged carcinogenic properties. It appears that cyclohexylamine, liberated from cyclamate as a result of bacterial mtabolism, is the proximate carcinogen. In an effort to elucidate the extent to which analogues of cyclamate would enter into the bacterial metabolic pathway, as well as any stereochemical requirements which might exist, several 2-alkaly analogues of sodium cyclamate were prepared. It was found that trans-N-(2-methylcyclohexyl)sulfamate (trans-2a) and trans-N-(2-ethylcyclohexyl)sulfamate were hydrolyzed by freshly collected fecal suspensions from rats fed cyclamate, but not from control rats, at the same rate as cyclamate itself. trans-N-(2-Isopropylcyclohexyl)sulfamate (trans-2c) was not hydrolyzed at all. Surprisingly, two of the analogous cis compounds (cis-2a and cis-2c, respectively) were hydrolyzed by fecal suspensions from control, as well as from cyclamate-fed, rats. Moreover, cis-2a was hydrolyzed by incubating it in medium only. Thus, it is apparent that stereochemical influences on the chemical properties of these compounds are substantial. These results do not appear to point the way toward a safe, nonmetabolizable sweetening agent.

Distribution of hexadecenoic, octadecenoic and octadecadienoic acid isomers in human tissue lipids.

PubMed

Adlof, R O; Emken, E A

1986-09-01

The trans 16:1, 18:1 and 18:2 fatty acid composition of various human organ lipids was studied to determine if isomers accumulated in specific tissues. "Trans" isomers are defined as those fatty acids containing one or more trans double bonds. Adipose, kidney, brain, heart and liver tissue lipids were analyzed. Gas chromatography with a 100-SP2560 capillary column was used to characterize the various positional and/or geometrical isomers. The distribution of trans 16:1 and 18:1 isomers ranged from 0.3% in the brain to 4.0% in adipose tissue, while trans 18:2 isomers ranged from 0.0% in the brain to 0.4% in adipose tissue. No trans 18:3 isomers were detected. Positional isomer ratios for cis 16:1 (delta 9 vs delta 7) and cis 18:1 (delta 11 vs delta 9) were also determined. Since these ratios are reproducible from one individual to the next, they might be useful for diagnosis of human metabolic disorders.

Formic acid dimers in a nitrogen matrix

NASA Astrophysics Data System (ADS)

Lopes, Susy; Fausto, Rui; Khriachtchev, Leonid

2018-01-01

Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (˜11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

Formic acid dimers in a nitrogen matrix.

PubMed

Lopes, Susy; Fausto, Rui; Khriachtchev, Leonid

2018-01-21

Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (∼11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

PubMed Central

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L.; Chen, Lin S.

2017-01-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types. PMID:29021290

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

PubMed

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

REMPI and MATI spectroscopy of cis and trans 4-chloro-3-fluoroanisole

NASA Astrophysics Data System (ADS)

Liu, Sheng; Dai, Wenshuai; Lin, Dan; Cheng, Min; Du, YiKui; Zhu, Qihe

2017-08-01

The Resonance-enhanced two-photon ionization (R2PI) and Mass-analyzed threshold ionization (MATI) spectra of 4-chloro-3-fluoroanisole (4Cl3FA) were recorded in detail. The experimental and calculated results revealed that cis and trans 4Cl3FA are the only two stable conformers in each of the S0, S1 and D0 states. The first electronic excitation energies (E1's) of cis and trans35Cl-4Cl3FA were measured to be 35,326 ± 3 and 35,443 ± 3 cm-1 by the R2PI spectroscopy and the corresponding adiabatic ionization energies (IEs) were determined to be 67,330 ± 5 and 67,591 ± 5 cm-1 by the MATI spectroscopy. The E1's and IEs of cis and trans37Cl-4Cl3FA were also obtained and found to be identical to that of the 35Cl-4Cl3FA conformers. Compared with the trans 4Cl3FA, the cis 4Cl3FA is more stable in the S0, S1 and D0 states. The vibrational bands observed in the R2PI and MATI spectra are related to the vibrations involving the in-plane deformation of the benzene ring, the CH3 torsion and the OCH3 inversion. The substituent effects on the molecular structures, transition energies and vibrations of 4Cl3FA are discussed.

Fatty acid profile, trans-octadecenoic, α-linolenic and conjugated linoleic acid contents differing in certified organic and conventional probiotic fermented milks.

PubMed

Florence, Ana Carolina R; Béal, Catherine; Silva, Roberta C; Bogsan, Cristina S B; Pilleggi, Ana Lucia O S; Gioielli, Luiz Antonio; Oliveira, Maricê N

2012-12-15

Development of dairy organic probiotic fermented products is of great interest as they associate ecological practices and benefits of probiotic bacteria. As organic management practices of cow milk production allow modification of the fatty acid composition of milk (as compared to conventional milk), we studied the influence of the type of milk on some characteristics of fermented milks, such as acidification kinetics, bacterial counts and fatty acid content. Conventional and organic probiotic fermented milks were produced using Bifidobacterium animalis subsp. lactis HN019 in co-culture with Streptococcus thermophilus TA040 and Lactobacillus delbrueckii subsp. bulgaricus LB340. The use of organic milk led to a higher acidification rate and cultivability of Lactobacillus bulgaricus. Fatty acids profile of organic fermented milks showed higher amounts of trans-octadecenoic acid (C18:1, 1.6 times) and polyunsaturated fatty acids, including cis-9 trans-11, C18:2 conjugated linoleic (CLA-1.4 times), and α-linolenic acids (ALA-1.6 times), as compared to conventional fermented milks. These higher levels were the result of both initial percentage in the milk and increase during acidification, with no further modification during storage. Finally, use of bifidobacteria slightly increased CLA relative content in the conventional fermented milks, after 7 days of storage at 4°C, whereas no difference was seen in organic fermented milks. Copyright © 2012 Elsevier Ltd. All rights reserved.

Conjugated fatty acid synthesis: residues 111 and 115 influence product partitioning of Momordica charantia conjugase.

PubMed

Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

2012-05-11

Conjugated linolenic acids (CLNs), 18:3 Δ(9,11,13), lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ(9,12,15)). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ(9cis,11trans,13cis)) or α-eleostearic acid (18:3 Δ(9cis,11trans,13trans)). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation.

On the effect of tether composition on cis/trans selectivity in intramolecular Diels-Alder reactions.

PubMed

Paddon-Row, Michael N; Longshaw, Alistair I; Willis, Anthony C; Sherburn, Michael S

2009-01-05

Intramolecular Diels-Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6-31+G(d) and CBS-QB3 levels of theory for a series of 1,3,8-nonatrienes, H(2)C=CH-CH=CH-CH(2)-X-Z-CH=CH(2) [-X-Z- = -CH(2)-CH(2)- (1); -O-C(=O)- (2); -CH(2)-C(=O)- (3); -O-CH(2)- (4); -NH-C(=O)- (5); -S-C(=O)- (6); -O-C(=S)- (7); -NH-C(=S)- (8); -S-C(=S)- (9)]. For each system studied (1-9), cis- and trans-TS isomers, corresponding, respectively, to endo- and exo-positioning of the -C-X-Z- tether with respect to the diene, have been located and their relative energies (E(rel) (TS)) employed to predict the cis/trans IMDA product ratio. Although the E(rel) (TS) values are modest (typically <3 kJ mol(-1)), they follow a clear and systematic trend. Specifically, as the electronegativity of the tether group X is reduced (X=O --> NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis-TS, namely (1) unfavorable torsional (eclipsing) strain about the C4-C5 bond, that is caused by the -C-X-C(=Y)- group's strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo-(thio)carbonyl group, C=Y, and the diene. The former interaction predominates when X is weakly electronegative (X=N, S), while the latter is dominant when X is more strongly electronegative (X=O), or a methylene group (X=CH(2)) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1, 2, 3, and 4 (published work) and 5, 6, and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans-selectivities in IMDAs that are normally only weakly selective

2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline: An amino acid in toxic peptides of Amanita virosa mushrooms

PubMed Central

Buku, A.; Faulstich, H.; Wieland, T.; Dabrowski, J.

1980-01-01

Among the four possible stereoisomers of 3,4-dihydroxy-L-proline,2,3-trans-3,4-trans-3,4-dihydroxy-L-proline (IV) had not been found in nature previously. It has now been detected as a component of virotoxins, toxic peptides of Amanita virosa mushrooms. Because periodate failed to effect an oxidative glycol splitting reaction, the two hydroxyl groups in positions 3 and 4 were expected to be in a trans configuration. Furthermore, the formation of a 4-lactone on treatment with acids pointed to the carboxyl group and the hydroxyl group at position 4 being in a cis configuration. These results are in agreement with structure IV only. Final proof for structure IV was given by NMR spectroscopy and direct comparison with the 2,3-cis-3,4-trans-3,4-dihydroxy-L-proline isomer. PMID:16592813

Diffusion of cis-5,8,11,14,17-eicosapentaenoic acid (1); carbon dioxide (2)

NASA Astrophysics Data System (ADS)

Winkelmann, J.

This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) cis-5,8,11,14,17-eicosapentaenoic acid; (2) carbon dioxide

Metabolism of Linoleic Acid by Barley Lipoxygenase and Hydroperoxide Isomerase 1

PubMed Central

Lulai, Edward C.; Baker, Charles W.; Zimmerman, Don C.

1981-01-01

The oxidation of linoleic acid in incubation mixtures containing extracts of barley lipoxygenase and hydroperoxide isomerase, and the production of these enzymes in quiescent and germinated barley, were investigated. The ratio of 9-hydroperoxylinoleic acid to 13-hydroperoxylinoleic acid was higher for incubation mixtures containing extracts of quiescent barley than for mixtures containing extracts of germinated barley; production of 13-hydroperoxylinoleic acid from germinated barley exceeded that of quiescent barley. Hydroperoxy metabolites of linoleic acid were converted to 9-hydroxy-10-oxo-cis-12-octadecenoic acid, 13-hydroxy-10-oxo-trans-11-octadecenoic acid, and small amounts of 11-hydroxy-12,13-epoxy-cis-9-octadecenoic acid and 11-hydroxy-9,10-epoxy-cis-13-octadecenoic acid whether quiescent or germinated barley was the enzyme source; a fifth product, 13-hydroxy-12-oxo-cis-9-octadecenoic acid was formed only when germinated barley was the enzyme source. Lipoxygenase was readily extracted by buffer, but hydroperoxide isomerase was bound in a catalytically active state to the insoluble barley grist and was efficiently extracted only when Triton X-100 was included in the extraction buffer. Hydroperoxide isomerase was localized in the embryo of quiescent barley, but it was present in the embryo, acrospire, and in small but concentrated amounts in the rootlet of germinating barley. The levels of both lipoxygenase and hydroperoxide isomerase increased through the thirteenth day of germination. Images PMID:16662032

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

PubMed

Cahoon, E B; Ripp, K G; Hall, S E; Kinney, A J

2001-01-26

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Therans-3-enoic acids ofAster alpinus andArctium minus seed oils.

PubMed

Morris, L J; Marshall, M O; Hammond, E W

1968-01-01

Thetrans-3-enoic acids ofAster alpinus (dwarf aster, rock aster) andArctium minus (burdock) seed oils have been isolated and characterized.Arctium seed oil containstrans-3,cis-9,cis-12-octadecatrienoic acid (9.9%), andAster oil containstrans-3-hexadecenoic (7.1%),rans-3-octadecenoic (1.9%),trans-3,cis-9-octadecadienoic (3.0%),a ndtrans-3,cis-9,cis-12-octadecatrienoic (13.7%) acids.Aster oil also has an epoxy acid as a minor constituent (ca. 2.0%), which has been identified ascis-9,10-epoxy-cis-12-octadecenoic acid.

Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors.

PubMed

Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

2015-10-01

Retinoid X receptors (RXRs) are ligand-controlled transcription factors which heterodimerize with other nuclear receptors to regulate gene transcriptions associated with crucial biological events. 9-cis retinoic acid (9cRA), which transactivates RXRs, is believed to be an endogenous RXR ligand. All-trans retinoic acid (ATRA) is a natural ligand for retinoic acid receptors (RARs), which heterodimerize with RXRs. Although the concentration of 9cRA in tissues is very low, ATRA is relatively abundant and some reports show that ATRA activates RXRs. We computationally studied the possibility of ATRA binding to RXRs using two different docking methods with our developed programs to assess the binding affinities of naturally occurring retinoids. The simulations showed good correlations to the reported binding affinities of these molecules for RXRs and RARs.

Density functional theory study of structural and electronic properties of trans and cis structures of thiothixene as a nano-drug.

PubMed

Noori Tahneh, Akram; Bagheri Novir, Samaneh; Balali, Ebrahim

2017-11-25

The geometrical structure, electronic and optical properties, electronic absorption spectra, vibrational frequencies, natural charge distribution, MEP analysis and thermodynamic properties of the trans and cis structures of the drug thiothixene were investigated using density functional theory (DFT) and time-dependent DFT (TDDFT) methods with the B3LYP hybrid functional and 6-311 + G(d,p) basis set. The results of the calculations demonstrate that the cis structure of thiothixene has appropriate quantum properties that can act as an active medicine. The relative energies of trans and cis structures of thiothixene shows that the cis structure is more stable than the trans structure, with a small energy difference. TDDFT calculations show that the cis structure of thiothixene has the best absorption properties. The calculated NLO properties show that the NLO properties of the cis structure of thiothixene are higher than the trans structure, and the fact that the chemical hardness of the cis structure is lower than that of the trans structure that indicates that the reactivity and charge transfer of the cis isomer of thiothixene is higher than that of trans thiothixene. The molecular electrostatic potential (MEP) maps of both structures of thiothixene demonstrate that the oxygen atoms of the molecule are appropriate areas for electrophilic reactions. The vibrational frequencies of the two conformations of thiothixene demonstrate that both structures of thiothixene have almost similar modes of vibrations. The calculated thermodynamic parameters show that these quantities increase with enhancing temperature due to the enhancement of molecular vibrational intensities with temperature. Graphical abstract Trans/Cis isomerization of thiothixene drug.

Pharmacokinetics and metabolism of all-trans- and 13-cis-retinoic acid in pulmonary emphysema patients.

PubMed

Muindi, Josephia R; Roth, Michael D; Wise, Robert A; Connett, John E; O'Connor, George T; Ramsdell, Joe W; Schluger, Neil W; Romkes, Marjorie; Branch, Robert A; Sciurba, Frank C

2008-01-01

Retinoids promote lung alveolarization in animal models and were administered to patients as part of the Feasibility of Retinoid Therapy for Emphysema (FORTE) study. This FORTE substudy investigated the pharmacokinetic profiles of 2 retinoic acid isomers-all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13-cRA)-in subjects with emphysema, evaluated strategies to overcome self-induced ATRA catabolism, and identified pharmacodynamic relationships. Comprehensive and limited pharmacokinetics were obtained at multiple visits in emphysema subjects treated with placebo (n = 30), intermittent dosing (4 days/week) with low-dose ATRA (1 mg/kg/day, n = 21), or high-dose ATRA (2 mg/kg/day, n = 25) or daily administration of 13-cRA (1 mg/kg/day, n = 40). High-dose ATRA produced the highest peak plasma ATRA Cmax. However, at follow-up, plasma ATRA C(max) was significantly decreased from baseline in subjects whose day 1 levels exceeded 100 ng/mL (P < .0001). In contrast, administration of 13-cRA produced lower plasma ATRA C(max) (<100 ng/mL), but the levels were significantly higher at follow-up than those on day 1 (P < .001). Plasma ATRA levels as determined on day 1 correlated with changes in pulmonary diffusing capacity at 6 months, consistent with concentration-dependent biologic effects (r2 = -0.25). The authors conclude that intermittent therapy with high-dose ATRA produced the greatest ATRA exposure, but alternative approaches for limiting self-induced ATRA catabolism should be sought.

Photoinduced Trans-to-cis Phase Transition of Polycrystalline Azobenzene at Low Irradiance Occurs in the Solid State

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

Bhattacharjee, Ujjal; Freppon, Daniel; Men, Long

2017-07-09

The ability to produce large-scale, reversible structural changes in a variety of materials by photoexcitation of a wide variety of azobenzene derivatives has been recognized for almost two decades. Because photoexcitation of trans-azobenzene produces the cis-isomer in solution, it has generally been inferred that the macroscopic structural changes occurring in materials are also initiated by a similar large-amplitude trans-to-cis isomerization. This paper provides the first demonstration that a trans-to-cis photoisomerization occurs in polycrystalline azobenzene, and is consistent with the previously hypothesized nature of the trigger in the photoactuated mechanisms of the materials in question. It is also demonstrated that undermore » low irradiance, trans-to-cis isomerization occurs in the solid (not via a pre-melted phase); and the presence of the cis-isomer thus lowers the melting point of the sample, providing a liquid phase. A variety of experimental techniques were employed, including X-ray diffraction measurements of polycrystalline azobenzene during exposure to laser irradiation and fluorescence measurements of the solid sample. Finally, a practical consequence of this work is that it establishes trans-azobenzene as an easily obtainable and well-defined control for monitoring photoinduced structural changes in X-ray diffraction experiments, using easily accessible laser wavelengths.« less

Comparison of milk fatty acid profiles measured on Kouri cows near Lake Chad and on dairy cattle as reported by meta-analytical data.

PubMed

Bada Algom, O; Fabry, C; Leroy, P L; Hornick, J-L

2017-06-01

Kouri (Bos taurus) is a breed aboriginal from Lake Chad and threatened with extinction. This study aimed to compare milk fatty acid profiles measured on Kouri cows and on high-yielding dairy cattle in Europe and elsewhere as reported by meta-analytical data (22 experimentations). Milk samples were collected from 14 Kouri dairy cows in dry season (March to June) and fatty acids (FA) were determined by gas chromatography. Overall, 32 FA have been identified. Kouri showed lower values (P < 0.001) in the sum of saturated FA (SFA, -10.9 pts), cis-9, cis-12 18:2 (-1.00 pt) (P < 0.01, higher values (P < 0.001) in the sum of monounsaturated FA (MUFA, +15.3 pts), C18:0) (+3.5 pts), cis-9, trans-11 C18:2-CLA (+1.00 pts), trans-11 18:1 (+1.4 pts) and (P < 0.01) in cis-9, C18:1 (+3.00 pts) acids. The differences between the milk FA profile of the Kouri cows and that obtained from meta-analytical data could be the possible consequence of the use of particular lake pastures by Kouri cows.

Synthesis and antioxidant activity of polyhydroxylated trans-restricted 2-arylcinnamic acids.

PubMed

Miliovsky, Mitko; Svinyarov, Ivan; Prokopova, Elena; Batovska, Daniela; Stoyanov, Simeon; Bogdanov, Milen G

2015-02-02

A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a-p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling 13C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds' structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon-carbon double bond. The antioxidant activity of compounds 3a-p was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH●), hydroxyl (OH●) and superoxide (O2●▬) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed.

Distinct Conformations of Ly49 Natural Killer Cell Receptors Mediate MHC Class I Recognition in Trans and Cis

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

Back, J.; Malchiodi, E; Cho, S

2009-01-01

Certain cell-surface receptors engage ligands expressed on juxtaposed cells and ligands on the same cell. The structural basis for trans versus cis binding is not known. Here, we showed that Ly49 natural killer (NK) cell receptors bound two MHC class I (MHC-I) molecules in trans when the two ligand-binding domains were backfolded onto the long stalk region. In contrast, dissociation of the ligand-binding domains from the stalk and their reorientation relative to the NK cell membrane allowed monovalent binding of MHC-I in cis. The distinct conformations (backfolded and extended) define the structural basis for cis-trans binding by Ly49 receptors andmore » explain the divergent functional consequences of cis versus trans interactions. Further analyses identified specific stalk segments that were not required for MHC-I binding in trans but were essential for inhibitory receptor function. These data identify multiple distinct roles of stalk regions for receptor function.« less

Serum trans-fatty acids level are positively associated with lower food security among american adults.

PubMed

Mazidi, Mohsen; Vatanparast, Hassan

2018-03-07

In the current study we aimed to assess whether the food security is associated with serum trans-fatty acids (TFAs) and dietary fat. Analyses were restricted to participants (from the US National Health and Nutrition Examination Survey) with data available on serum and diet TFAs and food security status from 2009 to 2010. All statistical analyses (analysis of covariance and linear regression) accounted for the survey design and sample weights. We included 3876 participants, overall (48.6%) participants were men, and (51.4%) were women, generally (69.0%) had high food security. Subjects with higher food security had a higher level of education as well (p < 0.001). Age-adjusted, sex-adjusted, race-adjusted, education-adjusted mean of trans 9-octadecenoic acid and trans-9, trans-12-octadecadienoic acid were higher in plasma of participants with lower food security (all p < 0.001), moreover in same model there was a significant positive association between plasma level of trans-11-octadecenoic acid, trans-9-octadecenoic acid and trans-9, trans-12-octadecadienoic acid and score of food security. Further, age, sex, race, education, and energy intake adjusted mean of dietary fatty acids show that total polyunsaturated fatty acids are higher in subjects with higher food security (p = 0.026) while, cholesterol consumption is higher in subjects with lower food security (p = 0.039). Our findings provide more evidence on the association between food insecurity and the higher level of TFAs in serum and different type of fat in the diet.

Effects of oil source and fish oil addition on ruminal biohydrogenation of fatty acids and conjugated linoleic acid formation in beef steers fed finishing diets.

PubMed

Duckett, S K; Gillis, M H

2010-08-01

Four Hereford steers (500 +/- 4.5 kg of BW) cannulated in the proximal duodenum were used to evaluate the effects of vegetable oil source or fish oil quantity on ruminal biohydrogenation (BH) and CLA outflow. Steers were fed 1 of 4 treatment diets in a 2 x 2 factorial arrangement of treatments (oil source: canola vs. corn oil; fish oil quantity: 0 or 1%) in a 4 x 4 Latin square design. The remainder of the diet included chopped bermudagrass hay, dry-rolled corn, and protein/mineral supplement. Duodenal samples were collected for 4 d after 11-d diet adaptation periods. Data were analyzed with animal, period, oil source, fish oil, and 2-way interaction among oil source and fish oil quantity in the model. All interactions among oil source and fish oil inclusion were nonsignificant with the exception of trans-11 vaccenic acid (TVA) and trans-9 octadecenoic acid. Intake and duodenal flow of total long-chain fatty acids did not differ between treatments. Apparent ruminal DM digestibility was not altered by oil source or fish oil inclusion. Apparent ruminal digestion of fatty acids did not differ among oil sources but was increased (P = 0.03) with fish oil supplementation. Ruminal BH of oleic and linolenic acids was increased (P = 0.01) for diets containing supplemental canola oil compared with corn oil. Ruminal BH of linoleic acid was greater (P = 0.01) for diets containing supplemental corn oil compared with canola oil. Fish oil addition reduced (P = 0.01) oleic acid BH but did not alter (P > 0.26) linoleic or linolenic acid BH. Duodenal flow of palmitic acid was greater (P = 0.05) for steers supplemented with corn oil compared with canola oil. Fish oil inclusion in the diet increased (P = 0.01) flow of n-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), trans-10 octadecenoic acid, trans-12 octadecenoic acid, and cis-9, trans-11 CLA. Trans-9 octadecenoic acid and TVA flows to the duodenum were increased (P = 0.01) when fish oil was

Potential energy profile, structural, vibrational and reactivity descriptors of trans-2-methoxycinnamic acid by FTIR, FT-Raman and quantum chemical studies

NASA Astrophysics Data System (ADS)

Arjunan, V.; Anitha, R.; Thenmozhi, S.; Marchewka, M. K.; Mohan, S.

2016-06-01

The stable conformers of trans-2-methoxycinnamic acid (trans-2MCA) are determined by potential energy profile analysis. The energies of the s-cis and s-trans conformers of trans-2MCA determined by B3LYP/cc-pVTZ method are -612.9788331 Hartrees and -612.9780953 Hartrees, respectively. The vibrational and electronic investigations of the stable s-cis and s-trans conformers of trans-2-methoxycinnamic acid have been carried out extensively with FTIR and FT-Raman spectral techniques. The s-cis conformer (I) with a (C16-C17-C18-O19) dihedral angle equal to 0° is found to be more favoured relative to the one s-trans (II) with (C16-C17-C18-O19) = 180°, possibly due to delocalization, hydrogen bonding and steric repulsion effects between the methoxy and acrylic acid groups. The DFT studies are performed with B3LYP method by utilizing 6-311++G** and cc-pVTZ basis sets to determine the structure, thermodynamic properties, vibrational characteristics and chemical shifts of the compound. The total dipole moments of the conformers determined by B3LYP/cc-pVTZ method are 3.35 D and 4.87 D for s-cis and s-trans, respectively. It reveals the higher polarity of s-trans conformer of trans-2MCA molecule. The electronic and steric influence of the methoxy group on the skeletal frequencies has been analysed. The energies of the frontier molecular orbitals and the LUMO-HOMO energy gap have been determined. The MEP of s-cis conformer lie in the range +1.374e × 10-2 to -1.374e × 10-2 while for s-trans it is +1.591e × 10-2 to -1.591e × 10-2. The total electron density of s-cis conformer lie in the range +5.273e × 10-2 to -5.273e × 10-2 while for s-trans it is +5.403e × 10-2 to -5.403e × 10-2. The MEP and total electron density shows that the s-cis conformer is less polar, less reactive and more stable than the s-trans conformer. All the reactivity descriptors of the molecule have been discussed. Intramolecular electronic interactions and their stabilisation energies have analysed

All-trans retinoic acid regulates hepatic bile acid homeostasis

PubMed Central

Yang, Fan; He, Yuqi; Liu, Hui-Xin; Tsuei, Jessica; Jiang, Xiaoyue; Yang, Li; Wang, Zheng-Tao; Wan, Yu-Jui Yvonne

2014-01-01

Retinoic acid (RA) and bile acids share common roles in regulating lipid homeostasis and insulin sensitivity. In addition, the receptor for RA (retinoid x receptor) is a permissive partner of the receptor for bile acids, farnesoid x receptor (FXR/NR1H4). Thus, RA can activate the FXR-mediated pathway as well. The current study was designed to understand the effect of all-trans RA on bile acid homeostasis. Mice were fed an all-trans RA-supplemented diet and the expression of 46 genes that participate in regulating bile acid homeostasis was studied. The data showed that all-trans RA has a profound effect in regulating genes involved in synthesis and transport of bile acids. All-trans RA treatment reduced the gene expression levels of Cyp7a1, Cyp8b1, and Akr1d1, which are involved in bile acid synthesis. All-trans RA also decreased the hepatic mRNA levels of Lrh-1 (Nr5a2) and Hnf4α (Nr2a1), which positively regulate the gene expression of Cyp7a1 and Cyp8b1. Moreover, all-trans RA induced the gene expression levels of negative regulators of bile acid synthesis including hepatic Fgfr4, Fxr, and Shp (Nr0b2) as well as ileal Fgf15. All-trans RA also decreased the expression of Abcb11 and Slc51b, which have a role in bile acid transport. Consistently, all-trans RA reduced hepatic bile acid levels and the ratio of CA/CDCA, as demonstrated by liquid chromatography-mass spectrometry. The data suggest that all-trans RA-induced SHP may contribute to the inhibition of CYP7A1 and CYP8B1, which in turn reduces bile acid synthesis and affects lipid absorption in the gastrointestinal tract. PMID:25175738

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition.

PubMed

Liu, Songling; Ren, Fazheng; Jiang, Jingli; Zhao, Liang

2016-07-28

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis-9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.

Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

PubMed Central

Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying

40 CFR 721.2250 - 1,4-Cyclohexanediamine, cis- and trans-.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-. 721.2250 Section 721.2250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2250 1,4-Cyclohexanediamine, cis- and trans-. (a) Chemical substances and significant new...

Higher immunoglobulin production in conjugated linoleic acid-supplemented rats during gestation and suckling.

PubMed

Ramírez-Santana, Carolina; Pérez-Cano, Francisco J; Castellote, Cristina; Castell, Margarida; Rivero, Montserrat; Rodríguez-Palmero, María; Franch, Angels

2009-09-01

Conjugated linoleic acid (CLA) has been reported to exert beneficial physiological effects on body composition and the immune system. However, little information is available on the influence of CLA on immune function during early life periods. The present study evaluates the effect of feeding an 80:20 mixture of cis-9, trans-11- and trans-10, cis-12-CLA isomers during gestation and suckling on the systemic immune response of weaned Wistar rats. Pups received dietary CLA from dams through the placental barrier and during suckling by breast milk (group A) or by oral administration (group B). Pups from group C only received CLA during suckling by oral administration. Group D constituted the reference group. Milk from dams fed the CLA diet had a high content of CLA and higher IgA and IgG concentrations than rats fed the standard diet. The plasma of pups from groups A, B and C showed six, twelve and nine times higher content of the cis-9, trans-11-CLA isomer than that of the group D pups. Rats from group A exhibited higher serum IgG concentrations than rats from the rest of the groups (22.14 (SEM 2.14) v. about 5 mg/ml; P < 0.05), whereas rats from groups A and B showed approximately 2-fold higher splenocyte IgM production than rats from groups C and D. However, CLA supplementation did not influence significantly the splenocyte proliferative response or cytokine secretion. Supplementation during gestation and suckling with an 80:20 cis-9, trans-11-trans-10, cis-12 CLA mix enhances the production of the main in vivo and in vitro Ig isotypes in Wistar rats.

Holographic recording materials development. [development of cis-trans isomerization for holographic memory

NASA Technical Reports Server (NTRS)

1974-01-01

Developments in the area of organic cis-trans isomerization systems for holographic memory applications are reported. The chemical research effort consisted of photochemical studies leading to the selection of a stilbene derivative and a polymer matrix system which have greatly improved refractive index differences between the cis and trans isomers as well as demonstrated efficiency of the photoisomerization process. In work on lithium niobate effects of sample stoichiometry and of read and write beam polarizations on recording efficiency were investigated. LiNbO3 was used for a study of angular sensitivity and of capability for simultaneous recording of extended objects without interference. The current status of LiNbO3 as a holographic recording material is summarized.

Effects of induced subacute ruminal acidosis on milk fat content and milk fatty acid profile.

PubMed

Enjalbert, F; Videau, Y; Nicot, M C; Troegeler-Meynadier, A

2008-06-01

Two lactating dairy cows fitted with a rumen cannula received successively diets containing 0%, 20%, 34% and again 0% of wheat on a dry matter basis. After 5, 10 and 11 days, ruminal pH was measured between 8:00 and 16:00 hours, and milk was analysed for fat content and fatty acid profile. Diets with 20% and 34% wheat induced a marginal and a severe subacute ruminal acidosis respectively. After 11 days, diets with wheat strongly reduced the milk yield and milk fat content, increased the proportions of C8:0 to C13:0 even- or odd-chain fatty acids, C18:2 n-6 and C18:3 n-3 fatty acids but decreased the proportions of C18:0 and cis-9 C18:1 fatty acids. Wheat also increased the proportions of trans-5 to trans-10 C18:1, the latter exhibiting a 10-fold increase with 34% of wheat compared with value during the initial 0% wheat period. There was also an increase of trans-10, cis-12 C18:2 fatty acid and a decrease of trans-11 to trans-16 C18:1 fatty acids. The evolution during adaptation or after return to a 0% wheat diet was rapid for pH but much slower for the fatty acid profile. The mean ruminal pH was closely related to milk fat content, the proportion of odd-chain fatty acids (linear relationship) and the ratio of trans-10 C18:1/trans-11 C18:1 (nonlinear relationship). Such changes in fatty acid profile suggested a possible use for non-invasive diagnosis of subacute ruminal acidosis.

Kinetics of photoirradiation-induced synthesis of soy oil-conjugated linoleic acid isomers.

PubMed

Jain, Vishal P; Proctor, Andrew

2007-02-07

Photoirradiation of soy oil with UV/visible light has been shown to produce significant amounts of trans,trans conjugated linoleic acid (CLA) isomers through conversion of various synthesized intermediate cis,trans isomers. The objective of this study was to determine the kinetics of CLA isomers synthesis to better understand the production of various isomers. Soy oil was irradiated with UV/visible light for 144 h in the presence of an iodine catalyst and CLA isomers analyzed by gas chromatography (GC). Arrhenius plots were developed for the conversion of soy oil linoleic acid (A) to form cis-, trans/trans-, cis-CLA (B), conversion of cis-, trans/trans-, cis-CLA to form trans,trans-CLA (C) with respect to B, and formation of trans,trans-CLA isomers with respect to C. The kinetics of consumption of linoleic acid (LA) to form cis-, trans/trans-, cis-CLA was found to be of second-order with a rate constant of 9.01 x 10-7 L/mol s. The rate of formation of cis-, trans/trans-, cis-CLA isomers depends on the rate of formation from LA and its rate of consumption to form trans,trans-CLA isomers. The conversion of cis-, trans/trans-, cis-CLA isomers to trans,trans-CLA isomers was found to be of first-order with a rate constant of 2.75 x 10-6 s-1. However, the formation of thermodynamically stable trans,trans-CLA isomers (C) with respect to C was found to be a zero-order reaction with a rate constant of 10.66 x 10-7 mol/L s. The consumption of LA was found to be the rate-determining step in the CLA isomers formation reaction mechanism. The findings provide a better understanding of the mechanism of CLA isomers synthesis by photoirradiation and the factors controlling the ratio of various isomers.

Docosahexaenoic Acid and Eicosapentaenoic Acid Did not Alter trans-10,cis-12 Conjugated Linoleic Acid Incorporation into Mice Brain and Eye Lipids.

PubMed

Vemuri, Madhuri; Adkins, Yuriko; Mackey, Bruce E; Kelley, Darshan S

2017-09-01

trans 10,cis 12-CLA has been reported to alter fatty acid composition in several non-neurological tissues, but its effects are less known in neurological tissues. Therefore, the purpose of this study was to determine if CLA supplementation would alter brain and eye fatty acid composition and if those changes could be prevented by concomitant supplementation with docosahexaenoic acid (DHA; 22:6n3) or eicosapentaenoic acid (EPA; 20:5n3). Eight-week-old, pathogen-free C57BL/6N female mice (n = 6/group) were fed either the control diet or diets containing 0.5% (w/w) t10,c12-CLA in the presence or absence of either 1.5% DHA or 1.5% EPA for 8 weeks. CLA concentration was significantly (P < 0.05) greater in the eye but not in the brain lipids of the CLA group when compared with the control group. The sums of saturated, monounsaturated, polyunsaturated fatty acids, and n3:n6 ratio did not differ between these two groups for both tissues. The n3:n6 ratio and concentrations of 20:5n3 and 22:5n3 were significantly greater, and those of 20:4n6, 22:4n6, and 22:5n6 were lesser in the CLA + DHA and CLA + EPA groups than in the control and CLA groups for either tissue. DHA concentration was higher in the CLA + DHA group only but not in the CLA + EPA group when compared with the CLA group for both tissues. The dietary fatty acids generally induced similar changes in brain and eye fatty acid concentration and at the concentrations used both DHA and EPA fed individually with CLA were more potent than CLA alone in altering the tissue fatty acid concentration.

CIS-TRANS ISOMERS OF VITAMIN A AND RETINENE IN THE RHODOPSIN SYSTEM

PubMed Central

Hubbard, Ruth; Wald, George

1952-01-01

Vitamin A and retinene, the carotenoid precursors of rhodopsin, occur in a variety of molecular shapes, cis-trans isomers of one another. For the synthesis of rhodopsin a specific cis isomer of vitamin A is needed. Ordinary crystalline vitamin A, as also the commercial synthetic product, both primarily all-trans, are ineffective. The main site of isomer specificity is the coupling of retinene with opsin. It is this reaction that requires a specific cis isomer of retinene. The oxidation of vitamin A to retinene by the alcohol dehydrogenase-cozymase system displays only a low degree of isomer specificity. Five isomers of retinene have been isolated in crystalline condition: all-trans; three apparently mono-cis forms, neoretinenes a and b and isoretinene a; and one apparently di-cis isomer, isoretinene b. Neoretinenes a and b were first isolated in our laboratory, and isoretinenes a and b in the Organic Research Laboratory of Distillation Products Industries. Each of these substances is converted to an equilibrium mixture of stereoisomers on simple exposure to light. For this reaction, light is required which retinene can absorb; i.e., blue, violet, or ultraviolet light. Yellow, orange, or red light has little effect. The single geometrical isomers of retinene must therefore be protected from low wave length radiation if their isomerization is to be avoided. By incubation with opsin in the dark, the capacity of each of the retinene isomers to synthesize rhodopsin was examined. All-trans retinene and neoretinene a are inactive. Neoretinene b yields rhodopsin indistinguishable from that extracted from the dark-adapted retina (λmax· 500 mµ). Isoretinene a yields a similar light-sensitive pigment, isorhodopsin, the absorption spectrum of which is displaced toward shorter wave lengths (λmax· 487 mµ). Isoretinene b appears to be inactive, but isomerizes preferentially to isoretinene a, which in the presence of opsin is removed to form isorhodopsin before the

Cis- and trans-zeatin differentially modulate plant immunity.

PubMed

Großkinsky, Dominik K; Edelsbrunner, Kerstin; Pfeifhofer, Hartwig; van der Graaff, Eric; Roitsch, Thomas

2013-07-01

Phytohormones are essential regulators of various processes in plant growth and development. Several phytohormones are also known to regulate plant responses to environmental stress and pathogens. Only recently, cytokinins have been demonstrated to play an important role in plant immunity. Increased levels of cytokinins such as trans-zeatin, which are considered highly active, induced resistance against mainly (hemi)biotrophic pathogens in different plant species. In contrast, cis-zeatin is commonly regarded as a cytokinin exhibiting low or no activity. Here we comparatively study the impact of both zeatin isomers on the infection of Nicotiana tabacum by the (hemi)biotrophic microbial pathogen Pseudomonas syringae. We demonstrate a biological effect of cis-zeatin and a differential effect of the two zeatin isomers on symptom development, defense responses and bacterial multiplication.

Short communication: rearrangement of rumenic Acid in ruminant fats: a marker of thermal treatment.

PubMed

Destaillats, F; Japiot, C; Chouinard, P Y; Arul, J; Angers, P

2005-05-01

Rumenic (cis-9,trans-11 18:2) acid is the main conjugated linoleic acid (CLA) isomer in milk and other ruminant fats. Anhydrous regular and high-CLA butterfats were heated at 200 degrees C for 2, 4, and 6 h under atmospheric conditions. [1,5] Sigmatropic isomerization of rumenic acid occurred, resulting in the formation of trans-8,cis-10 18:2 acid, as determined by mass spectrometry of its 4,4-dimethyloxazoline derivative. Rate of isomerization was monitored by gas-liquid chromatography, using a 120-m capillary column coated with 70% equivalent cyanoalkylpolysiloxane polymer, and reaction was of first order. Furthermore, [1,5] sigmatropic rearrangement product analysis can be used as an indicator of heat treatment of natural fats and oils containing CLA.

Analysis of cis and trans 3-Methylfentanyl by Liquid Chromatography High Resolution Mass Spectrometry and Findings in Forensic Toxicology Casework.

PubMed

Fogarty, Melissa F; Papsun, Donna M; Logan, Barry K

2018-05-25

3-Methylfentanyl (3-MF), N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared in the United States illicit drug market since its disappearance after a series of overdose deaths in 1988.3-MF presents an analytical challenge, due to presence of cis and trans stereoisomers, each with different potencies, and ultimately very low concentrations in the blood after use. A method was developed using liquid chromatography time-of-flight mass spectrometry for the analysis of (±)-cis-3-MF and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem cases and 2 human performance case involving 3-MF were submitted for quantitative analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL (±0.81) and 0.66 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting (±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting (±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total amount of 3-MF present in the case with the resulting average concentration at 1.28 ng/mL (±1.16), median at 1 ng/mL and range 0.18-5.18. As the estimated dose of this compound is approximately 0.1-0.5 mg with the resulting concentrations in the sub-nanogram range, it is necessary for forensic toxicology laboratories to obtain instruments sensitive enough to detect these substances in driving under the influence of drugs and postmortem cases. Quantitation of 3-MF with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more specific toxicological interpretation. This article is protected by copyright. All rights reserved.

Dissecting relative contributions of cis- and trans-determinants to nucleosome distribution by comparing Tetrahymena macronuclear and micronuclear chromatin.

PubMed

Xiong, Jie; Gao, Shan; Dui, Wen; Yang, Wentao; Chen, Xiao; Taverna, Sean D; Pearlman, Ronald E; Ashlock, Wendy; Miao, Wei; Liu, Yifan

2016-12-01

The ciliate protozoan Tetrahymena thermophila contains two types of structurally and functionally differentiated nuclei: the transcriptionally active somatic macronucleus (MAC) and the transcriptionally silent germ-line micronucleus (MIC). Here, we demonstrate that MAC features well-positioned nucleosomes downstream of transcription start sites and flanking splice sites. Transcription-associated trans-determinants promote nucleosome positioning in MAC. By contrast, nucleosomes in MIC are dramatically delocalized. Nucleosome occupancy in MAC and MIC are nonetheless highly correlated with each other, as well as with in vitro reconstitution and predictions based upon DNA sequence features, revealing unexpectedly strong contributions from cis-determinants. In particular, well-positioned nucleosomes are often matched with GC content oscillations. As many nucleosomes are coordinately accommodated by both cis- and trans-determinants, we propose that their distribution is shaped by the impact of these nucleosomes on the mutational and transcriptional landscape, and driven by evolutionary selection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Conjugated linoleic acid synthesis-related protein proteasome subunit α 5 (PSMA5) is increased by vaccenic acid treatment in goat mammary tissue.

PubMed

Jin, Y C; Li, Z H; Hong, Z S; Xu, C X; Han, J A; Choi, S H; Yin, J L; Zhang, Q K; Lee, K B; Kang, S K; Song, M K; Kim, Y J; Kang, H S; Choi, Y J; Lee, H G

2012-08-01

This study was conducted to identify proteins associated with the endogenous synthesis of conjugated linoleic acid (CLA) from trans-vaccenic acid (TVA; trans-11 C18:1, a precursor for CLA endogenous synthesis) in mammary tissues. Six lactating goats were divided into 2 groups. One group was given an intravenous bolus injection of TVA (150mg) twice daily over 4 d; the other group received saline injections. Treatment with TVA increased the concentration of cis-9,trans-11 CLA and TVA in goat milk. Additionally, TVA treatment increased the expression of stearoyl-CoA desaturase (SCD) in mammary tissue. Using 2-dimensional gel electrophoresis and electrospray ionization quadrupole time-of-flight mass spectrometry, 3 proteins affected by infusions of TVA were identified. Proteasome (prosome, macropain) subunit α type 5 (PSMA5) was upregulated, whereas peroxiredoxin-1 and translationally controlled tumor protein 1 were downregulated in TVA-treated animals compared with the vehicle-injected controls. Only the effect of TVA on PSMA5 could be confirmed by Western blot analysis. To further explore the regulation of PSMA5 in mammary epithelial cells when TVA is converted into CLA, we used a differentiated bovine mammary epithelial cell line treated with TVA for 6h. Changes in cis-9,trans-11 CLA concentrations and mRNA expression patterns of both SCD and PSMA5 were monitored. The concentration of cis-9,trans-11 CLA increased after TVA treatment. The mRNA expression level of PSMA5 was significantly elevated to 6h, but SCD mRNA expression only increased in 2h after TVA treatment. These results indicate that PSMA5 is highly expressed in goat mammary tissue and bovine mammary epithelial cells when TVA is converted into CLA. Our data suggest that PSMA5 protein is associated with CLA biosynthesis in mammary tissue. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Supplementation of increasing amounts of linseed oil to dairy cows fed total mixed rations: effects on digestion, ruminal fermentation characteristics, protozoal populations, and milk fatty acid composition.

PubMed

Benchaar, C; Romero-Pérez, G A; Chouinard, P Y; Hassanat, F; Eugene, M; Petit, H V; Côrtes, C

2012-08-01

The effect of linseed oil (LO) supplementation on nutrient digestibility, forage (i.e., timothy hay) in sacco ruminal degradation, ruminal fermentation characteristics, protozoal populations, milk production, and milk fatty acid (FA) profile in dairy cows was investigated. Four ruminally cannulated, primiparous lactating cows were used in a 4 × 4 Latin square design (28-d periods). They were fed a total mixed ration (50:50 forage:concentrate (F:C) ratio [dry matter (DM) basis] without supplementation (control, CTL), or supplemented (wt/wt; DM basis) with LO at 2, 3, or 4%. Supplementation with LO had no effect on DM intake (19 kg/d) and apparent total-tract digestibility of nutrients (organic matter, neutral detergent fiber, acid detergent fiber, starch, and gross energy). Ruminal pH, ammonia, and total volatile FA concentrations were not changed by LO supplementation to diets. Extent of changes in volatile FA pattern and effective ruminal degradability of DM of timothy hay were minor. Neither the total numbers nor the genera distribution of protozoa was changed by the addition of increasing amounts of LO to the diet. Milk yield increased linearly (26.1, 27.3, 27.4, and 28.4 kg/d for CTL to LO4, respectively) as the amount of LO added to the diet increased. Milk fat content was not affected by LO supplementation, whereas milk protein content decreased linearly with increasing amounts of LO in the diet. Milk fat proportions of several intermediates of ruminal biohydrogenation of polyunsaturated FA (i.e., trans-10 18:1, trans-11 18:1, cis-9,trans-11 18:2, trans-11,cis-15 18:2, and cis-9,trans-11,cis-15 18:3) increased linearly with LO addition to the diet. The proportion of cis-9,cis-12 18:2 decreased linearly (2.06, 1.99, 1.91, and 1.83% for CTL to LO4, respectively) as the amount of LO in the diet increased. Milk fat content of cis-9,cis-12,cis-15 18:3 increased as the level of LO in the diet increased up to 3% but no further increase was observed when 4% of LO

Identification of absolute geometries of cis and trans molecular isomers by Coulomb Explosion Imaging.

PubMed

Ablikim, Utuq; Bomme, Cédric; Xiong, Hui; Savelyev, Evgeny; Obaid, Razib; Kaderiya, Balram; Augustin, Sven; Schnorr, Kirsten; Dumitriu, Ileana; Osipov, Timur; Bilodeau, René; Kilcoyne, David; Kumarappan, Vinod; Rudenko, Artem; Berrah, Nora; Rolles, Daniel

2016-12-02

An experimental route to identify and separate geometric isomers by means of coincident Coulomb explosion imaging is presented, allowing isomer-resolved photoionization studies on isomerically mixed samples. We demonstrate the technique on cis/trans 1,2-dibromoethene (C 2 H 2 Br 2 ). The momentum correlation between the bromine ions in a three-body fragmentation process induced by bromine 3d inner-shell photoionization is used to identify the cis and trans structures of the isomers. The experimentally determined momentum correlations and the isomer-resolved fragment-ion kinetic energies are matched closely by a classical Coulomb explosion model.

Identification of absolute geometries of cis and trans molecular isomers by Coulomb Explosion Imaging

PubMed Central

Ablikim, Utuq; Bomme, Cédric; Xiong, Hui; Savelyev, Evgeny; Obaid, Razib; Kaderiya, Balram; Augustin, Sven; Schnorr, Kirsten; Dumitriu, Ileana; Osipov, Timur; Bilodeau, René; Kilcoyne, David; Kumarappan, Vinod; Rudenko, Artem; Berrah, Nora; Rolles, Daniel

2016-01-01

An experimental route to identify and separate geometric isomers by means of coincident Coulomb explosion imaging is presented, allowing isomer-resolved photoionization studies on isomerically mixed samples. We demonstrate the technique on cis/trans 1,2-dibromoethene (C2H2Br2). The momentum correlation between the bromine ions in a three-body fragmentation process induced by bromine 3d inner-shell photoionization is used to identify the cis and trans structures of the isomers. The experimentally determined momentum correlations and the isomer-resolved fragment-ion kinetic energies are matched closely by a classical Coulomb explosion model. PMID:27910943

Identification of absolute geometries of cis and trans molecular isomers by Coulomb Explosion Imaging

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

Ablikim, Utuq; Bomme, Cédric; Xiong, Hui

An experimental route to identify and separate geometric isomers by means of coincident Coulomb explosion imaging is presented, allowing isomer-resolved photoionization studies on isomerically mixed samples. We demonstrate the technique on cis/trans 1,2-dibromoethene (C 2H 2Br 2). The momentum correlation between the bromine ions in a three-body fragmentation process induced by bromine 3d inner-shell photoionization is used to identify the cis and trans structures of the isomers. Lastly, the experimentally determined momentum correlations and the isomer-resolved fragment-ion kinetic energies are matched closely by a classical Coulomb explosion model.

Identification of absolute geometries of cis and trans molecular isomers by Coulomb Explosion Imaging

DOE PAGES

Ablikim, Utuq; Bomme, Cédric; Xiong, Hui; ...

2016-12-02

An experimental route to identify and separate geometric isomers by means of coincident Coulomb explosion imaging is presented, allowing isomer-resolved photoionization studies on isomerically mixed samples. We demonstrate the technique on cis/trans 1,2-dibromoethene (C 2H 2Br 2). The momentum correlation between the bromine ions in a three-body fragmentation process induced by bromine 3d inner-shell photoionization is used to identify the cis and trans structures of the isomers. Lastly, the experimentally determined momentum correlations and the isomer-resolved fragment-ion kinetic energies are matched closely by a classical Coulomb explosion model.

IRIS Toxicological Review of Cis-& Trans-1,2-Dichloroethylene (Final Report)

EPA Science Inventory

EPA has finalized the Toxicological Review of cis- & trans-1,2-Dichloroethylene: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

Trans Fatty Acids

NASA Astrophysics Data System (ADS)

Doyle, Ellin

1997-09-01

Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

PubMed

Sharma, Anežka; Bányiová, Katarína; Vrana, Branislav; Justan, Ivan; Čupr, Pavel

2017-11-01

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

Effect of breed and production system on the content of cis-9, trans-11 CLA in m. longissimus lumborum and m. Semimembranosus of lambs

USDA-ARS?s Scientific Manuscript database

Fatty acid composition of meat animal tissues has significant human dietary implications. Katahdin (KK), Katahdin x Suffolk (KS), Suffolk x Katahdin (SK), and Suffolk (SS) wether lambs (n=24) born spring of 2007 were used to evaluate levels of Conjugated Linolcic Acid (C18:2c9t11) from longissimus ...

The relationship of plasma Trans fatty acids with dietary inflammatory index among US adults.

PubMed

Mazidi, Mohsen; Gao, Hong-Kai; Shivappa, Nitin; Wirth, Michael D; Hebert, James R; Kengne, Andre Pascal

2017-08-04

It has been suggested that trans fatty acids (TFAs) play an important role in cardiovascular diseases. We investigated the association between plasma TFAs and the dietary inflammatory index (DII) ™ in US adults. National Health and Nutrition Examination Survey (NHANES) participants with data on plasma TFAs measured from 1999 to 2010 were included. Energy-adjusted-DII ™ (E-DII ™) expressed per 1000 kcal was calculated from 24-h dietary recalls. All statistical analyses accounted for the survey design and sample weights. Of the 5446 eligible participants, 46.8% (n = 2550) were men. The mean age of the population was 47.1 years overall, 47.8 years for men and 46.5 years for women (p = 0.09). After adjustment for C-reactive protein, body-mass-index, smoking, race, age, education, and marital status in linear regressions, trans 9-hexadecenoic acid [β coefficient 0.068 (95% CI: 0.032 to 0.188)], trans 11-octadecenoic acid [β coefficient 0.143 (95% CI: 0.155 to 0.310)], trans 9-octadecenoic acid [β coefficient 0.122 (95% CI: 0.120 to 0.277)], trans 9, and trans 12-octadienoic acid [β coefficient 0.103 (95% CI: 0.090 to 0.247)] were positively associated with the DII (all p < 0.001). The association of plasma TFAs with a marker of dietary inflammation suggests an underlying mechanism in the initiation and progression of cardiovascular diseases.

Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations.

PubMed

Intlekofer, Andrew M; Shih, Alan H; Wang, Bo; Nazir, Abbas; Rustenburg, Ariën S; Albanese, Steven K; Patel, Minal; Famulare, Christopher; Correa, Fabian M; Takemoto, Naofumi; Durani, Vidushi; Liu, Hui; Taylor, Justin; Farnoud, Noushin; Papaemmanuil, Elli; Cross, Justin R; Tallman, Martin S; Arcila, Maria E; Roshal, Mikhail; Petsko, Gregory A; Wu, Bin; Choe, Sung; Konteatis, Zenon D; Biller, Scott A; Chodera, John D; Thompson, Craig B; Levine, Ross L; Stein, Eytan M

2018-06-27

Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the pathogenesis of acute myeloid leukaemia (AML) through the production of the oncometabolite 2-hydroxyglutarate (2HG) 1-8 . Enasidenib (AG-221) is an allosteric inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG by IDH2 mutants 9,10 . In a phase I/II clinical trial, enasidenib inhibited the production of 2HG and induced clinical responses in relapsed or refractory IDH2-mutant AML 11 . Here we describe two patients with IDH2-mutant AML who had a clinical response to enasidenib followed by clinical resistance, disease progression, and a recurrent increase in circulating levels of 2HG. We show that therapeutic resistance is associated with the emergence of second-site IDH2 mutations in trans, such that the resistance mutations occurred in the IDH2 allele without the neomorphic R140Q mutation. The in trans mutations occurred at glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface where enasidenib binds to the IDH2 dimer. The expression of either of these mutant disease alleles alone did not induce the production of 2HG; however, the expression of the Q316E or I319M mutation together with the R140Q mutation in trans allowed 2HG production that was resistant to inhibition by enasidenib. Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). Our observations uncover a mechanism of acquired resistance to a targeted therapy and underscore the importance of 2HG production in the pathogenesis of IDH-mutant malignancies.

IRIS Toxicological Review of Cis-& Trans-1,2-Dichloroethylene (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of cis- and trans-1,2-dichloroethylene that will appear in the Integrated Risk Information System (IRIS) database.

Effect of CLA and other C18 unsaturated fatty acids on DGAT in bovine milk fat biosynthetic systems.

PubMed

Sørensen, Brent M; Chris Kazala, E; Murdoch, Gordon K; Keating, Aileen F; Cruz-Hernandez, Cristina; Wegner, Jochen; Kennelly, John J; Okine, Erasmus K; Weselake, Randall J

2008-10-01

Production of dairy products with increased amounts of nutraceutic FA such as conjugated linoleic acid (CLA) represents a recent approach for dairy producers and processors to increase the value of their products. The effect of CLA and other FA on the expression of diacylglycerol acyltransferase-1 (DGAT-1) and DGAT-2, and DGAT activity were investigated in bovine mammary gland epithelial (MAC-T) cells. DGAT gene expression analyses were also conducted using bovine mammary gland tissue from dairy cows. In the studies with MAC-T cells, there were no significant effects of CLA isomers or other FA on DGAT1 expression, whereas all FA tested showed enhanced DGAT2 expression (P < 0.05 to P < 0.001), with alpha-linolenic acid (alpha-18:3) having the greatest effect. Additionally, DGAT2 expression was co-ordinated with expression of lysophosphatidic acid acyltransferase (LPAAT), an observation that was also apparent in mammary gland from lactating dairy cows. In contrast, treatment of MAC-T cells with trans-10, cis-12 18:2 or alpha-18:3 resulted in a significant (P < 0.05) decrease in overall DGAT enzyme activity, although the mechanisms resulting in these effects are unclear. Competition assays using microsomes from bovine mammary gland tissue and 1-[(14)C]oleoyl-CoA suggested that DGAT activity was more selective for oleoyl (cis-9 18:1)-CoA than cis-9, trans-11 18:2-, trans-10, cis-12 18:2- or cis-9, cis-12 18:2-CoA. Collectively, the results suggest the relationship between trans-10, cis-12 18:2 and reduced TAG production in bovine milk is not linked to the production of DGAT1 or DGAT2 transcripts, but probably involves effects of this CLA isomer at events beyond transcription, such as post-translational and/or enzyme activity effects.

Miocene tectonism and the separation of cis- and trans-Andean river basins: Evidence from Neotropical fishes

NASA Astrophysics Data System (ADS)

Albert, James S.; Lovejoy, Nathan R.; Crampton, William G. R.

2006-03-01

The fish fauna of trans-Andean river basins in northwestern South America is ancient and diverse, including 14% (558 of 4,085) of all Neotropical teleost species and representing 88% of the orders and 79% of the families. The evolutionary histories of these lineages provide many examples to test models of the tectonic uplift that isolated the trans-Andean basins. We report the results of two newly compiled data sets of phylogenetic and biogeographic information on the freshwater fishes of the region: (1) species-level phylogenies for 26 Neotropical freshwater teleost taxa, with a minimum of 37 cis-/trans-Andean clades and (2) species distributions for 641 genera of Neotropical freshwater teleosts, with a minimum of 140 cis-/trans-Andean clades. Although it provides only about one-quarter the total number of cis-/trans-Andean clades, species phylogeny preserves a more accurate record of the temporal sequence of basin isolation. Phylogenies using gene sequences also may provide estimates on the timing of lineage divergences. However, the great majority (70%) of available species phylogenies for Neotropical freshwater teleosts employ comparative morphology alone, partly because species-level sampling for most taxa requires collections over large spatial (10 3-10 4 km) scales, and collections of whole specimens for morphological study are readily available for many taxa from natural history museums. Fish species phylogenies are partially concordant with patterns of drainage basin isolation generated from geological data on the Miocene of northwestern South America, which associate the initial rise of the Eastern Cordillera (˜1 2 Ma) with the hydrological isolation of the Magdalena and Pacific Slope regions and the rise of the Merida Andes (˜8 Ma) with the isolation of the modern Maracaibo and Orinoco basins. Although some phylogenies unite taxa from the Maracaibo and cis-Andean Orinoco, a more common set of area relationships occurs between clades exclusive to the

Randomized Subspace Learning for Proline Cis-Trans Isomerization Prediction.

PubMed

Al-Jarrah, Omar Y; Yoo, Paul D; Taha, Kamal; Muhaidat, Sami; Shami, Abdallah; Zaki, Nazar

2015-01-01

Proline residues are common source of kinetic complications during folding. The X-Pro peptide bond is the only peptide bond for which the stability of the cis and trans conformations is comparable. The cis-trans isomerization (CTI) of X-Pro peptide bonds is a widely recognized rate-limiting factor, which can not only induces additional slow phases in protein folding but also modifies the millisecond and sub-millisecond dynamics of the protein. An accurate computational prediction of proline CTI is of great importance for the understanding of protein folding, splicing, cell signaling, and transmembrane active transport in both the human body and animals. In our earlier work, we successfully developed a biophysically motivated proline CTI predictor utilizing a novel tree-based consensus model with a powerful metalearning technique and achieved 86.58 percent Q2 accuracy and 0.74 Mcc, which is a better result than the results (70-73 percent Q2 accuracies) reported in the literature on the well-referenced benchmark dataset. In this paper, we describe experiments with novel randomized subspace learning and bootstrap seeding techniques as an extension to our earlier work, the consensus models as well as entropy-based learning methods, to obtain better accuracy through a precise and robust learning scheme for proline CTI prediction.

Protein and energy metabolism of young male Wistar rats fed conjugated linoleic acid as structured triacylglycerol.

PubMed

Jørgensen, Henry; Hansen, Christina Hørup; Mu, Huiling; Jakobsen, Kirsten

2010-08-01

Twelve 4-week-old male Wistar rats weighing 100 g were fed diets semi-ad libitum for 22 d containing either 1.5% conjugated linoleic acid (CLA-diet) or high oleic sunflower oil (Control-diet). The CLA was structured triacylglycerol with predominantly cis-9, trans-11 and trans-10, cis-12 fatty acid isomers in the inner position and oleic acid in the other positions of the glycerol molecule. The rats were kept individually in metabolic cages. From days 8-16 energy, nitrogen (N) and carbon (C) balances as well as gas exchange measurements in open-air circuit respiration chambers were performed. CLA had no significant influence on feed intake, daily gain in weight or feed conversion efficiency, but the digestibility of nutrients and energy was significantly reduced (except for fat). CLA did not affect N-balance, but reduced the level of daily retained fat (RQ-method: 0.107 vs. 0.417 g/d, p < 0.01) and consequently energy retention in fat. This was explained by increased heat production (HP, RQ-method: 224.6 vs. 214.6 kJ/d, p < 0.001) caused by a higher fat oxidation (28.9% vs. 22.3%, p < 0.001) at the expense of oxidation of carbohydrates (65.6% vs. 71.4%, p < 0.001), while there was no significant effect on the oxidation of protein (5.5% vs. 6.3%). Consequently, the non-protein respiratory quotient (RQnp) was lower in the rats fed the CLA-diet than in the rats fed the Control-diet (0.907 vs. 0.928, p < 0.001). Plasma total lipids of the CLA-fed rats had higher concentrations of the cis-9, trans-11 than the trans-10, cis-12 CLA-isomer. This study shows that young male Wistar rats respond to CLA fed as structured triacylglycerol.

Determinants of Chromosome Architecture: Insulator Pairing in cis and in trans

PubMed Central

Fujioka, Miki; Mistry, Hemlata; Schedl, Paul; Jaynes, James B.

2016-01-01

The chromosomes of multicellular animals are organized into a series of topologically independent looped domains. This domain organization is critical for the proper utilization and propagation of the genetic information encoded by the chromosome. A special set of architectural elements, called boundaries or insulators, are responsible both for subdividing the chromatin into discrete domains and for determining the topological organization of these domains. Central to the architectural functions of insulators are homologous and heterologous insulator:insulator pairing interactions. The former (pairing between copies of the same insulator) dictates the process of homolog alignment and pairing in trans, while the latter (pairing between different insulators) defines the topology of looped domains in cis. To elucidate the principles governing these architectural functions, we use two insulators, Homie and Nhomie, that flank the Drosophila even skipped locus. We show that homologous insulator interactions in trans, between Homie on one homolog and Homie on the other, or between Nhomie on one homolog and Nhomie on the other, mediate transvection. Critically, these homologous insulator:insulator interactions are orientation-dependent. Consistent with a role in the alignment and pairing of homologs, self-pairing in trans is head-to-head. Head-to-head self-interactions in cis have been reported for other fly insulators, suggesting that this is a general principle of self-pairing. Homie and Nhomie not only pair with themselves, but with each other. Heterologous Homie-Nhomie interactions occur in cis, and we show that they serve to delimit a looped chromosomal domain that contains the even skipped transcription unit and its associated enhancers. The topology of this loop is defined by the heterologous pairing properties of Homie and Nhomie. Instead of being head-to-head, which would generate a circular loop, Homie-Nhomie pairing is head-to-tail. Head-to-tail pairing in cis

Dietary docosahexaenoic acid and trans-10, cis-12-conjugated linoleic acid alter oxylipins profiles in mouse adipose tissue

USDA-ARS?s Scientific Manuscript database

Diets containing high amounts of n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some n-3 PUFA-a...

A canonical discriminant analysis to study the association between milk fatty acids of ruminal origin and milk fat depression in dairy cows.

PubMed

Conte, G; Dimauro, C; Serra, A; Macciotta, N P P; Mele, M

2018-04-04

Although milk fat depression (MFD) has been observed and described since the beginning of the last century, all the molecular and biochemical mechanisms involved are still not completely understood. Some fatty acids (FA) originating during rumen biohydrogenation have been proposed as causative elements of MFD. However, contradictory results were obtained when studying the effect of single FA on MFD. An alternative could be the simultaneous evaluation of the effect of many FA using a multivariate approach. The aim of this study was to evaluate the relationship between individual milk FA of ruminal origin and MFD using canonical discriminant analysis, a multivariate technique able to distinguish 2 or more groups on the basis of a pool of variables. In a commercial dairy herd, a diet containing 26% starch on a DM basis induced an unintentional MFD syndrome in 14 cows out of 40. Milk yielded by these 14 animals showed a fat content lower than 50% of the ordinary value, whereas milk production and protein content were normal. The remaining 26 cows secreted typical milk fat content and therefore were considered the control group, even though they ate the same diet. The stepwise discriminant analysis selected 14 milk FA of ruminal origin most able to distinguish the 2 groups. This restricted pool of FA was used, as variables, in a run of the canonical discriminant analysis that was able to significantly discriminate between the 2 groups. Out of the 14 FA, 5 conjugated linoleic acid isomers (C18:2 trans-10,trans-12, C18:2 trans-8,trans-10, C18:2 trans-11,cis-13, C18:2 cis-9,cis-11, C18:2 cis-10,cis-12) and C15:0 iso were more related to the control group, whereas C18:2 trans-10,cis-12, C16:1 trans-6-7, C16:1 trans-9, C18:1 trans-6-8, C18:1 trans-9, C18:1 trans-10, C18:1 cis-11, and C18:3n-3 were positively associated with the MFD group, allowing a complete discrimination. On the basis of these results, we can conclude that (1) the shift of ruminal biohydrogenation from C18

Effect of the inclusion of quebracho tannins in a diet rich in linoleic acid on milk fatty acid composition in dairy ewes.

PubMed

Toral, P G; Hervás, G; Belenguer, A; Bichi, E; Frutos, P

2013-01-01

Despite controversy surrounding the ability of tannins to modulate the fatty acid (FA) profile of ruminant-derived products, reports on this issue are still very limited for dairy sheep. This study was conducted to examine the effect of the inclusion of quebracho tannins in a diet rich in linoleic acid on ewe performance and milk FA composition. Thirty-six lactating ewes were distributed into 6 lots and allocated to 2 treatments (3 lots/treatment): control or quebracho. All sheep received a total mixed ration based on alfalfa hay and a concentrate (forage:concentrate ratio of 40:60) supplemented with 20 g of sunflower oil/kg of dry matter plus 0 (control diet) or 20 g of an extract of quebracho tannins/kg of dry matter (QUE diet). Milk production and composition were analyzed on d 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27 on treatments, and milk FA profile on d 0, 3, 6, 12, 18, and 27. On d 27, samples of rumen fluid were collected for pH, and lactate, ammonia, and volatile FA concentration analysis. Feeding the QUE diet had no apparent effect on animal performance and hardly modified ruminal fermentation characteristics, except for a reduction in the molar proportions of minor volatile FA. Dietary tannins increased the milk concentration of several 18:1 and 18:2 isomers and decreased that of branched-chain FA. Some of these changes were relatively constant throughout the experiment (e.g., cis-12 18:1 and trans-9,cis-12 18:2), whereas others varied over time (e.g., trans-10 18:1, which increased gradually with the QUE diet). Significant differences between treatments in trans-11 18:1 and cis-9,trans-11 conjugated linoleic acid were only observed on d 3. Overall, addition of quebracho tannins to a diet rich in linoleic acid did not prove useful to beneficially modify milk FA composition, especially over the long term. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

How does the trans-cis photoisomerization of azobenzene take place in organic solvents?

PubMed

Tiberio, Giustiniano; Muccioli, Luca; Berardi, Roberto; Zannoni, Claudio

2010-04-06

The trans-cis photoisomerization of azobenzene-containing materials is key to a number of photomechanical applications, but the actual conversion mechanism in condensed phases is still largely unknown. Herein, we study the n, pi* isomerization in a vacuum and in various solvents via a modified molecular dynamics simulation adopting an ab initio torsion-inversion force field in the ground and excited states, while allowing for electronic transitions and a stochastic decay to the fundamental state. We determine the trans-cis photoisomerization quantum yield and decay times in various solvents (n-hexane, anisole, toluene, ethanol, and ethylene glycol), and obtain results comparable with experimental ones where available. A profound difference between the isomerization mechanism in vacuum and in solution is found, with the often neglected mixed torsional-inversion pathway being the most important in solvents.

Influence of pH on the cis- trans isomerization of Valine-Proline dipeptide: An integrated NMR and theoretical investigation

NASA Astrophysics Data System (ADS)

Ivanova, Galya; Yakimova, Boryana; Angelova, Silvia; Stoineva, Ivanka; Enchev, Venelin

2010-06-01

The pH influence on the cis- trans isomerization of the Valine-Proline dipeptide was investigated by means of NMR spectral techniques and quantum chemical calculations at different computational levels. It was found that the process of isomerization is strongly pH dependent. The trans-isomer of Val-Pro is the more abundant isomer when the amino group is protonated, while an approximately equal distribution between the cis and trans-isomers for the neutral and anion forms of the dipeptide was confirmed.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the endogenous metabolism of all-trans-retinoic acid in the rat.

PubMed

Schmidt, Carsten K; Hoegberg, Pi; Fletcher, Nicholas; Nilsson, Charlotte B; Trossvik, Christina; Håkansson, Helen; Nau, Heinz

2003-07-01

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is known to influence vitamin A homeostasis. In order to investigate the mechanism behind this retinoid disruption, male Sprague-Dawley rats were exposed to TCDD at doses ranging from 0.1 to 100 micro g/kg body weight, and were killed 3 days after exposure. Additional groups of rats were killed 1 and 28 days after a single oral dose of 10 micro g TCDD/kg body weight. Serum, kidney, and liver were investigated for retinoid levels, as well as gene expression and enzyme activities relevant for retinoid metabolism. Besides the well known effects of TCDD on apolar retinoids, i.e. decreased hepatic and increased renal retinyl ester (RE) levels, we have found dose-dependent elevation of all- trans-retinoic acid (all- trans-RA) levels in all investigated tissues. In the liver, 9- cis-4-oxo-13,14-dihydro-RA was drastically decreased by TCDD in a dose-dependent manner. In serum, cis-isomers of all- trans-RA, including 9,13-di- cis-RA, were significantly reduced already at the lowest dose level. Protein and mRNA levels of cellular retinol binding protein I (CRBP-I) in liver or kidneys were not significantly altered by TCDD exposure at doses at which retinoid levels were affected, making CRBP-I an unlikely candidate to account for the alterations in retinoid metabolism caused by TCDD. The expression and activities of relevant cytochrome P450 (CYP) enzymes with potential roles in all- trans-RA synthesis and/or degradation (CYP1A1, 1A2, and 2B1/2) were also monitored. A possible role of CYP1A1 in TCDD-induced all- trans-RA synthesis is suggested from the time-course relationship between CYP1A1 activity and all- trans-RA levels in liver and kidney. The significant alteration of the all- trans-RA metabolism has the potential to contribute significantly to the toxicity of TCDD.

Formation and characterization of a multicomponent equilibrium system derived from cis- and trans-1-aminomethylcyclohexane-1,2-diol.

PubMed

Hetényi, Anasztázia; Szakonyi, Zsolt; Klika, Karel D; Pihlaja, Kalevi; Fülöp, Ferenc

2003-03-21

Both cis and trans isomers of amino diols 3-6 were prepared stereoselectively. In the reactions between 3-6 and phenyl isothiocyanate, the ring closure proceeded regioselectively and resulted only in spiro derivatives of 2-phenyliminooxazolidines 9, 10, 13, and 14. The reaction of cis- (or trans-)1-aminomethylcyclohexane-1,2-diol 4 (or 6) with 1 equiv of an aromatic aldehyde 15a-g in EtOH at room temperature resulted in a complex, multicomponent equilibrium mixture of 16a-g and 18a-g (or 17a-g and 19a-g), in each case consisting of a five-component, ring-chain tautomeric system 16A-E (or 17A-E), involving the Schiff base, two epimeric spirooxazolidines, two epimeric condensed 1,3-oxazines, and some of the four tricyclic compounds 18A-D (or 19A-D). The five-component, ring-chain equilibria were found to be adequately described by the Hammett-Brown linear free energy equation.

trans-trans Conjugated linoleic acid enriched soybean oil reduces fatty liver and lowers serum cholesterol in obese zucker rats.

PubMed

Gilbert, William; Gadang, Vidya; Proctor, Andrew; Jain, Vishal; Devareddy, Latha

2011-10-01

Conjugated linoleic acid (CLA) is a collection of octadecadienoic fatty acids that have been shown to possess numerous health benefits. The CLA used in our study was produced by the photoisomerization of soybean oil and consists of about 20% CLA; this CLA consists of 75% trans-trans (a mixture of t8,t10; t9,t11; t10,t12) isomers. This method could be readily used to increase the CLA content of all soybean oil used as a food ingredient. The objective of this study was to determine the effects of trans-trans CLA-rich soy oil, fed as a dietary supplement, on body composition, dyslipidemia, hepatic steatosis, and markers of glucose control and liver function of obese fa/fa Zucker rats. The trans-trans CLA-rich soy oil lowered the serum cholesterol and low density lipoprotein-cholesterol levels by 41 and 50%, respectively, when compared to obese controls. Trans-trans CLA-rich soy oil supplementation also lowered the liver lipid content significantly (P < 0.05) with a concomitant decrease in the liver weight in the obese rats. In addition, glycated hemoglobin values were improved in the group receiving CLA-enriched soybean oil in comparison to the obese control. PPAR-γ expression in white adipose tissue was unchanged. In conclusion, trans-trans CLA-rich soy oil was effective in lowering total liver lipids and serum cholesterol.

Effect of grape seed extract, Cistus ladanifer L., and vegetable oil supplementation on fatty acid composition of abomasal digesta and intramuscular fat of lambs.

PubMed

Jerónimo, Eliana; Alves, Susana P; Dentinho, Maria T P; Martins, Susana V; Prates, José A M; Vasta, Valentina; Santos-Silva, José; Bessa, Rui J B

2010-10-13

Thirty-six lambs were used in a 6 week experiment to evaluate the effect of vegetable oil blend supplementation (0 vs 60 g/kg of dry matter (DM)) and two dietary condensed tannin sources, grape seed extract (0 vs 25 g/kg of DM) and Cistus ladanifer L. (0 vs 250 g/kg of DM), on fatty acid (FA) composition of abomasal digesta and intramuscular polar and neutral lipids. Grape seed extract did not affect the FA profile of abomasal digesta or muscle lipid fractions. C. ladanifer had a minor effect in lambs fed diets with no oil but greatly changed the abomasal and muscle FA profiles in oil-supplemented lambs. It decreased 18:0 and increased 18:1 trans-11 in abomasal digesta and increased 18:1 trans-11 and 18:2 cis-9,trans-11 (P = 0.062) in muscle neutral lipids, resulting in an important enrichment of meat 18:2 cis-9,trans-11 when compared to other oil-supplemented diets (19.2 vs 41.7 mg/100 g of muscle).

Replacing cereals with dehydrated citrus pulp in a soybean oil supplemented diet increases vaccenic and rumenic acids in ewe milk.

PubMed

Santos-Silva, José; Dentinho, Maria T; Francisco, Alexandra; Portugal, Ana P; Belo, Ana T; Martins, António P L; Alves, Susana P; Bessa, Rui J B

2016-02-01

This study evaluates the effect of the replacement of cereals by dried citrus pulp (DCP) in diets supplemented with 5% of soybean oil, on ewe milk yield and composition, including milk fatty acid (FA). Four Serra da Estrela multiparous ewes in the second month of lactation were used in a double 2×2 Latin square design. Ewes were individually penned and milked twice a day with an 8-h interval. Each experimental period included 14 d of diet adaptation followed by 5d of measurements and sampling. The 2 diets included on dry matter basis 450 g/kg of corn silage and 550 g/kg of either a soybean oil-supplemented concentrate meal containing barley and maize (cereal) or dried citrus pulp (DCP; citrus). Feed was offered ad libitum, considering 10% of orts, and intake was measured daily. Milk yield was higher and dry matter intake tended to be higher with the citrus diet. Milk composition and technological properties for cheese production were not affected by treatments, except for lactose, which was lower with the citrus diet. Replacement of cereals by DCP resulted in a 3-percentage-point decrease of both 18:0 and cis-9-18:1 that were mostly compensated by the 4.19- and 1.68-percentage-point increases of trans-11-18:1 and cis-9,trans-11-18:2, respectively. The intake of C18 FA tended to increase with the citrus diet compared with the cereal diet, but the apparent transfer of 18:2n-6 and of 18:3n-3 did not differ between diets. The milk output of C18 FA increased with the citrus compared with the cereal diet, mostly due to the increase of trans-11-18:1 and cis-9,trans-11-18:2 because the daily milk output of 18:0, trans-10-18:1, cis-9-18:1, 18:2n-6 and 18:3n-3 did not differ between diets. Replacing cereals with DCP in an oil-supplemented diet resulted in a selective increase of trans-11-18:1 and cis-9,trans-11-18:2 in milk, with no major effect on other biohydrogenation intermediates. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All

Proline cis-trans isomerization and its implications for the dimerization of analogues of cyclopeptide stylostatin 1: a combined computational and experimental study.

PubMed

López-Martínez, C; Flores-Morales, P; Cruz, M; González, T; Feliz, M; Diez, A; Campanera, Josep M

2016-05-14

Cis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)), a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates. Primarily, cyclo-(KSTAIPF) and cyclo-(RSTAIPF) showed specific trends in circular dichroism, MALDI-TOF and HPLC purification experiments, which suggests the occurrence of peptide dimerization. Meanwhile, the NMR spectrum of cyclo-(KSTAIPF) indicates that this cyclopeptide exists in the two slow-exchange families of conformations mentioned above. Molecular dynamics simulations combined with quantum mechanical calculations have shed light on the factors governing the cis/trans conformational ratio. In particular, we have found that residue mutations affect the internal hydrogen bond pattern which ultimately tunes the cis/trans conformational ratio and that only trans conformers are capable of aggregating due to the shape complementarity of the two subunits.

Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats.

PubMed

Martins, Susana V; Lopes, Paula A; Alfaia, Cristina M; Rodrigues, Pedro O; Alves, Susana P; Pinto, Rui M A; Castro, Matilde F; Bessa, Rui J B; Prates, José A M

2010-03-01

Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2 % cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1 % of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-alpha and IL-1beta. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition.

Diversity of Δ12 Fatty Acid Desaturases in Santalaceae and Their Role in Production of Seed Oil Acetylenic Fatty Acids*

PubMed Central

Okada, Shoko; Zhou, Xue-Rong; Damcevski, Katherine; Gibb, Nerida; Wood, Craig; Hamberg, Mats; Haritos, Victoria S.

2013-01-01

Plants in the Santalaceae family, including the native cherry Exocarpos cupressiformis and sweet quandong Santalum acuminatum, accumulate ximenynic acid (trans-11-octadecen-9-ynoic acid) in their seed oil and conjugated polyacetylenic fatty acids in root tissue. Twelve full-length genes coding for microsomal Δ12 fatty acid desaturases (FADs) from the two Santalaceae species were identified by degenerate PCR. Phylogenetic analysis of the predicted amino acid sequences placed five Santalaceae FADs with Δ12 FADs, which include Arabidopsis thaliana FAD2. When expressed in yeast, the major activity of these genes was Δ12 desaturation of oleic acid, but unusual activities were also observed: i.e. Δ15 desaturation of linoleic acid as well as trans-Δ12 and trans-Δ11 desaturations of stearolic acid (9-octadecynoic acid). The trans-12-octadecen-9-ynoic acid product was also detected in quandong seed oil. The two other FAD groups (FADX and FADY) were present in both species; in a phylogenetic tree of microsomal FAD enzymes, FADX and FADY formed a unique clade, suggesting that are highly divergent. The FADX group enzymes had no detectable Δ12 FAD activity but instead catalyzed cis-Δ13 desaturation of stearolic acid when expressed in yeast. No products were detected for the FADY group when expressed recombinantly. Quantitative PCR analysis showed that the FADY genes were expressed in leaf rather than developing seed of the native cherry. FADs with promiscuous and unique activities have been identified in Santalaceae and explain the origin of some of the unusual lipids found in this plant family. PMID:24062307

Diversity of Δ12 fatty acid desaturases in santalaceae and their role in production of seed oil acetylenic fatty acids.

PubMed

Okada, Shoko; Zhou, Xue-Rong; Damcevski, Katherine; Gibb, Nerida; Wood, Craig; Hamberg, Mats; Haritos, Victoria S

2013-11-08

Plants in the Santalaceae family, including the native cherry Exocarpos cupressiformis and sweet quandong Santalum acuminatum, accumulate ximenynic acid (trans-11-octadecen-9-ynoic acid) in their seed oil and conjugated polyacetylenic fatty acids in root tissue. Twelve full-length genes coding for microsomal Δ12 fatty acid desaturases (FADs) from the two Santalaceae species were identified by degenerate PCR. Phylogenetic analysis of the predicted amino acid sequences placed five Santalaceae FADs with Δ12 FADs, which include Arabidopsis thaliana FAD2. When expressed in yeast, the major activity of these genes was Δ12 desaturation of oleic acid, but unusual activities were also observed: i.e. Δ15 desaturation of linoleic acid as well as trans-Δ12 and trans-Δ11 desaturations of stearolic acid (9-octadecynoic acid). The trans-12-octadecen-9-ynoic acid product was also detected in quandong seed oil. The two other FAD groups (FADX and FADY) were present in both species; in a phylogenetic tree of microsomal FAD enzymes, FADX and FADY formed a unique clade, suggesting that are highly divergent. The FADX group enzymes had no detectable Δ12 FAD activity but instead catalyzed cis-Δ13 desaturation of stearolic acid when expressed in yeast. No products were detected for the FADY group when expressed recombinantly. Quantitative PCR analysis showed that the FADY genes were expressed in leaf rather than developing seed of the native cherry. FADs with promiscuous and unique activities have been identified in Santalaceae and explain the origin of some of the unusual lipids found in this plant family.

Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study.

PubMed

Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J; Peeters, Petra H M; Slimani, Nadia

2015-01-01

Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

PubMed Central

Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J.; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J.; Peeters, Petra H.M.; Slimani, Nadia

2015-01-01

Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids. PMID:25675445

Prepartum supplementation of conjugated linoleic acids (CLA) increased milk energy output and decreased serum fatty acids and β-hydroxybutyrate in early lactation dairy cows

PubMed Central

Oliveira, Rafael Caputo; Pralle, Ryan S.; de Resende, Lucas C.; Nova, Carlos Henrique P. C.; Caprarulo, Valentina; Jendza, Joshua A.; Troescher, Arnulf

2018-01-01

Prepartum supplementation with conjugated linoleic acid (CLA) may influence lipolysis and hyperketonemia in dairy cows. The objective of this study was to examine the effect of prepartum CLA supplementation on lactation performance and serum fatty acids (FA) and β-hydroxybutyrate (BHB) in early lactation dairy cows, and secondarily on reproductive performance. Multiparous cows were enrolled in the study at 18 days prior to expected calving date, and randomly assigned 100 g/day of Lutrell Pure (BASF, Ludwigshafen, Germany; 75% FA), providing 10 g/day of each CLA isomer (trans-10 cis-12 and cis-9 trans-11 CLA) or equivalent amount of rumen inert fatty acids as control (78 g/day of Energy Booster 100; Milk Specialties Global, Eden Prairie, MN). Treatments were top dressed daily to individual cows from enrollment to calving and all cows were offered the same ration. Blood samples were collected on the first day of supplementation, 10 days prepartum, and 1, 7, 14, and 30 days postpartum. Hyperketonemia was defined as serum BHB ≥ 1.2 mM. Milk yield was recorded daily until 60 days postpartum and averaged weekly. Milk samples were obtained weekly for component analysis. Prepartum CLA supplementation tended to increase serum concentration of cis-9, trans-11 CLA and increased trans-10, cis-12 CLA prepartum. Cows supplemented with CLA had increased milk protein yield and tended to have increased milk fat yield and milk yield, which together resulted in greater energy content of milk. Cows supplemented with CLA had lower serum FA on day 1 and 7 postpartum and overall lower serum BHB postpartum, which resulted in decreased prevalence of hyperketonemia on day 14 postpartum. There were no differences in body condition score change, other health disorders, or reproductive outcomes by treatment. Together, these findings indicate that prepartum CLA supplementation may be a plausible strategy to positively influence postpartum performance. PMID:29772023

Hydroperoxide Lyase and Other Hydroperoxide-Metabolizing Activity in Tissues of Soybean, Glycine max

PubMed Central

Gardner, Harold W.; Weisleder, David; Plattner, Ronald D.

1991-01-01

Hydroperoxide lyase (HPLS) activity in soybean (Glycine max) seed/seedlings, leaves, and chloroplasts of leaves required detergent solubilization for maximum in vitro activity. On a per milligram of protein basis, more HPLS activity was found in leaves, especially chloroplasts, than in seeds or seedlings. The total yield of hexanal from 13(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid (13S-HPOD) from leaf or chloroplast preparations was 58 and 66 to 85%, respectively. Because of significant competing hydroperoxide-metabolizing activities from other enzymes in seed/seedling preparations, the hexanal yields from this source were lower (36-56%). Some of the products identified from the seed or seedling preparations indicated that the competing activity was mainly due to both a hydroperoxide peroxygenase and reactions catalyzed by lipoxygenase. Different HPLS isozyme compositions in the seed/seedling versus the leaf/chloroplast preparations were indicated by differences in the activity as a function of pH, the Km values, relative Vmax with 13S-HPOD and 13(S)-hydroperoxy-cis-9,trans-11,cis-15-octadecatrienoic acid (13S-HPOT), and the specificity with different substrates. With regard to the latter, both seed/seedling and chloroplast HPLS utilized the 13S-HPOD and 13S-HPOT substrates, but only seeds/seedlings were capable of metabolizing 9(S)-hydroperoxy-trans-10,cis-12-octadecadienoic acid into 9-oxononanoic acid, isomeric nonenals, and 4-hydroxynonenal. From 13S-HPOD and 13S-HPOT, the products were identified as 12-oxo-cis-9-dodecenoic acid, as well as hexanal from 13S-HPOD and cis-3-hexenal from 13S-HPOT. In seed preparations, there was partial isomerization of the cis-3 or cis-9 into trans-2 or trans-10 double bonds, respectively. PMID:16668490

Trans-cis switching mechanisms in proline analogues and their relevance for the gating of the 5-HT3 receptor.

PubMed

Melis, Claudio; Bussi, Giovanni; Lummis, Sarah C R; Molteni, Carla

2009-09-03

Trans-cis isomerization of a proline peptide bond is a potential mechanism to open the channel of the 5-HT(3) receptor. Here, we have used the metadynamics method to theoretically explore such a mechanism. We have determined the free energy surfaces in aqueous solution of a series of dipeptides of proline analogues and evaluated the free energy difference between the cis and trans isomers. These theoretical results were then compared with data from mutagenesis experiments, in which the response of the 5-HT(3) receptor was measured when the proline at the apex of the M2-M3 transmembrane domain loop was mutated. The strong correlation between the experimental and the theoretical data supports the existence of a trans-cis proline switch for opening the 5-HT(3) receptor ion channel.

Structure of the cyclic peptide [W8S]contryphan Vn: effect of the tryptophan/serine substitution on trans-cis proline isomerization.

PubMed

Nepravishta, Ridvan; Mandaliti, Walter; Melino, Sonia; Eliseo, Tommaso; Paci, Maurizio

2014-12-01

The structural characterization of [W8S]contryphan Vn, an analogue of Contryphan Vn with tryptophan 8 substituted with a serine residue (W8S), was performed by NMR spectroscopy, molecular dynamics simulations and fluorescence spectroscopy. Contryphan Vn, a bioactive cyclic peptide from the venom of the cone snail Conus ventricosus, contains an S-S bridge between two cysteines and a D-tryptophan. Like other Contryphans, [W8S]contryphan Vn has proline 7 isomerized trans, while the proline 4 has nearly equivalent populations of cis and trans configurations. The thermodynamic and kinetic parameters of the trans-cis isomerization of proline 4 were measured. The isomers of [W8S]contryphan Vn with proline 4 in cis and trans show structural differences. The absence of the salt bridge between the same Asp2 and Lys6, present in Contryphan Vn, may be attributed to the lack of the hydrophobic side chain of Trp8 where it likely protects the electrostatic interactions. These results may contribute to identifying, in these cyclic peptides, the structural determinants of the mechanism of proline trans-cis isomerization, this being also an important step in protein folding.

Molecular dynamics simulations of cis-trans isomerization for a proline-containing tripeptide in solution

NASA Astrophysics Data System (ADS)

Wan, Shun Zhou; Wang, Cun Xin; Xu, Ying Wu; Shi, Yun Yu

1996-11-01

The cis-trans isomerization of X-Pro (X is Pro or any other residue) often plays a rate-limiting role in protein folding. In order to study the dynamic properties of X-Pro in water, we have analyzed the trajectory data obtained from constrained molecular dynamics (MD) simulations of a tripeptide Phe-Pro-Ala in solution. Via calculation of autocorrelation functions and their corresponding spectral densities, we have found that the structural fluctuations of the solute are affected by the motions of various degrees of freedom, and the solvent dynamic behavior is bimodal rather than exponential or Gaussian. In addition, according to the energy and torque analysis, we suggest that both the anti/endo and the syn/endo could be the possible transition state for the cis-trans isomerization of the tripeptide.

Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells.

PubMed

Armstrong, J L; Ruiz, M; Boddy, A V; Redfern, C P F; Pearson, A D J; Veal, G J

2005-02-28

Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 microM) or R116010 (1 or 10 microM) in combination with either 10 microM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma.

Phosphorylation effects on cis/trans isomerization and the backbone conformation of serine-proline motifs: accelerated molecular dynamics analysis.

PubMed

Hamelberg, Donald; Shen, Tongye; McCammon, J Andrew

2005-02-16

The presence of serine/threonine-proline motifs in proteins provides a conformational switching mechanism of the backbone through the cis/trans isomerization of the peptidyl-prolyl (omega) bond. The reversible phosphorylation of the serine/threonine modulates this switching in regulatory proteins to alter signaling and transcription. However, the mechanism is not well understood. This is partly because cis/trans isomerization is a very slow process and, hence, difficult to study. We have used our accelerated molecular dynamics method to study the cis/trans proline isomerization, preferred backbone conformation of a serine-proline motif, and the effects of phosphorylation of the serine residue. We demonstrate that, unlike normal molecular dynamics, the accelerated molecular dynamics allows for the system to escape very easily from the trans isomer to cis isomer, and vice versa. Moreover, for both the unphosphorylated and phosphorylated peptides, the statistical thermodynamic properties are recaptured, and the results are consistent with experimental values. Isomerization of the proline omega bond is shown to be asymmetric and strongly dependent on the psi backbone angle before and after phosphorylation. The rates of escape decrease after phosphorylation. Also, the alpha-helical backbone conformation is more favored after phosphorylation. This accelerated molecular dynamics approach provides a general approach for enhancing the conformational transitions of molecular systems without having prior knowledge of the location of the minima and barriers on the potential-energy landscape.

Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry.

PubMed

Nisar, Madiha; Wong, Lawrence W Y; Sung, Herman H Y; Haynes, Richard K; Williams, Ian D

2018-06-01

The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0 4,13 .0 8,13 ]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C 15 H 23 NO 4 ·C 9 H 8 O 2 ). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C 15 H 23 NO 4 ·C 4 H 4 O 4 ), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza 2 :Mal (3, 2C 15 H 23 NO 4 ·C 4 H 4 O 4 ). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza 2 :Fum (4). All cocrystal formation appears driven by acid-lactam R 2 2 (8) heterosynthons with short O-H...O=C hydrogen bonds [O...O = 2.56 (2) Å], augmented by weaker C=O...H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.

Metabolomic fingerprinting of primed tobacco cells provide the first evidence for the biological origin of cis-chlorogenic acid.

PubMed

Mhlongo, M I; Piater, L A; Steenkamp, P A; Madala, N E; Dubery, I A

2015-01-01

Previous studies suggest that only trans-isomers of chlorogenic acid (CGA) are naturally produced. Cis-isomers have been noted in some plant tissues exposed to different mechanical processes as well as untreated tobacco leaves exposed to sunlight. Very little, however, is known about the biological significance and origin of cis-isomers. Here we show for the first time the accumulation of cis-5-caffeoylquinic acid in cultured tobacco cells treated with different inducers of plant defence (lipopolysaccharides, flagellin peptide-22, chitosan, acibenzolar-S-methyl and isonitrosoacetophenone), without exposure to UV light and with a 2-fold (on average) increase in the concentration of the pool in comparison to non-stimulated cells. Our UHPLC-Q-TOF-MS and multivariate statistical results suggest the presence of a possible biological pathway responsible for the production of cis-CGAs in tobacco plants.

Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells.

PubMed

Sharma, Anežka; Bányiová, Katarína; Babica, Pavel; El Yamani, Naouale; Collins, Andrew Richard; Čupr, Pavel

2017-09-01

2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25μgmL -1 . trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25μgmL -1 . The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and trans-EHMC was detected at the concentration 25μgmL -1 . The No observed adverse effect level (NOAEL, mg kg -1 bwday -1 ) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL trans-EHMC =3.07, NOAEL cis-EHMC =0.30 for TK-6 and NOAEL trans-EHMC =26.46, NOAEL cis-EHMC =20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RfD, mgkg -1 bwday -1 ) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HI cis-EHMC was 7 times higher than HI trans-EHMC . In terms of CDI, relative contributions were; dermal exposure route>oral>inhalation. According to our results we recommend the RfD trans-EHMC =0.20 and RfD cis-EHMC =0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs. Copyright © 2017 Elsevier B

IRIS Toxicological Review of cis- & trans-1,2-Dichloroethylene (Interagency Science Consultation Draft)

EPA Science Inventory

On September 24, 2009, the Toxicological Review of cis- and trans-1,2-dichloroethylene and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal ag...

Effects of butter naturally enriched with conjugated linoleic acid and vaccenic acid on blood lipids and LDL particle size in growing pigs.

PubMed

Haug, Anna; Sjøgren, Per; Hølland, Nina; Müller, Hanne; Kjos, Nils P; Taugbøl, Ole; Fjerdingby, Nina; Biong, Anne S; Selmer-Olsen, Eirik; Harstad, Odd M

2008-08-29

Cow milk is a natural source of the cis 9, trans 11 isomer of conjugated linoleic acid (c9,t11-CLA) and trans vaccenic acid (VA). These fatty acids may be considered as functional foods, and the concentration in milk can be increased by e.g. sunflower oil supplementation to the dairy cow feed. The objective of this study was to compare the effects of regular butter with a special butter naturally enriched in c9,t11-CLA and VA on plasma lipids in female growing pigs. The experimental period lasted for three weeks and the two diets provided daily either 5.0 g c9,t11-CLA plus 15.1 g VA or 1.3 g c9,t11-CLA plus 3.6 g VA. The serum concentrations of c9,t11-CLA, VA and alpha-linolenic acid were increased and myristic (14:0) and palmitic acid (16:0) were reduced in the pigs fed the CLA+VA-rich butter-diet compared to regular butter, but no differences in plasma concentrations of triacylglycerol, cholesterol, HDL-cholesterol, LDL-cholesterol, LDL particle size distribution or total cholesterol/HDL cholesterol were observed among the two dietary treatment groups. Growing pigs fed diets containing butter naturally enriched in about 20 g c9,t11-CLA plus VA daily for three weeks, had increased serum concentrations of alpha-linolenic acid and decreased myristic and palmitic acid compared to pigs fed regular butter, implying a potential benefit of the CLA+VA butter on serum fatty acid composition. Butter enriched in CLA+VA does not appear to have significant effect on the plasma lipoprotein profile in pigs.

NTP toxicology and carcinogensis Studies of 2,4-hexadienal (89% trans,trans isomer, CAS No. 142-83-6; 11% cis,trans isomer) (Gavage Studies).

PubMed

2003-10-01

2,4-Hexadienal, a colorless to yellow liquid with a pungent "green" or citrus odor, is used as a food additive for flavor enhancement, as a fragrance agent, as a starting material or intermediate in synthetic reactions in the chemical and pharmaceutical industries, as a fumigant, and as a corrosion inhibitor for steel. 2,4-Hexadienal was nominated for study by the National Cancer Institute because of the potential for carcinogenicity based on its alpha,beta-unsaturated aldehyde structure and the potential link between exposure to lipid peroxidation products in the diet and human malignancies. The commercial product is a mixture containing chiefly trans,trans-2,4-hexadienal in equilibrium with cis,trans-2,4-hexadienal. Male and female F344/N rats and B6C3F1 mice received 2,4-hexadienal (89% trans,trans; 11% cis,trans) in corn oil by gavage for 16 days, 14 weeks, or 2 years. Tissues and plasma from dosed rats were examined for malondialdehyde and glutathione concentrations, and DNA adducts were characterized in liver and forestomach samples from dosed rats and mice. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 3, 9, 27, 80, or 240 mg 2,4-hexadienal/kg body weight in corn oil by gavage, 5 days per week, for 16 days. Three male and three female 240 mg/kg rats died before the end of the study. Mean body weight gains of 240 mg/kg rats were significantly less than those of the vehicle controls. Clinical findings included diarrhea, ataxia, lethargy, and nasal/eye discharge in males, and lethargy, paleness, and abnormal breathing in females in the 240 mg/kg groups. Liver weights of 240 mg/kg females were significantly greater than those of the vehicle controls. Gross and microscopic lesions indicative of forestomach necrosis and ulceration were present in most 240 mg/kg rats, and forestomach

Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors

PubMed Central

Fleming, Michael S; Vysochan, Anna; Paixão, Sόnia; Niu, Jingwen; Klein, Rüdiger; Savitt, Joseph M; Luo, Wenqin

2015-01-01

RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling. DOI: http://dx.doi.org/10.7554/eLife.06828.001 PMID:25838128

IRIS Toxicological Review of cis- & trans-1,2-Dichloroethylene (Interagency Science Discussion Draft)

EPA Science Inventory

EPA is releasing the draft report, Toxicological Review of cis-1,2-Dichloroethylene and trans-1,2-Dichloroethylene, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the Synthesis and structural and photoswitchable properties of novel chiral host molecules: axis chiral 2,2'-dihydroxy-1,1'-binaphthyl-appended stiff-stilbene.

PubMed

Shimasaki, Toshiaki; Kato, Shin-ichiro; Ideta, Keiko; Goto, Kenta; Shinmyozu, Teruo

2007-02-16

Novel photoswitchable chiral hosts having an axis chiral 2,2'-dihydroxy-1,1'-binaphthyl (BINOL)-appended stiff-stilbene, trans-(R,R)- and -(S,S)-1, were synthesized by palladium-catalyzed Suzuki-Miyaura coupling and low-valence titanium-catalyzed McMurry coupling as key steps, and they were fully characterized by various NMR spectral techniques. The enantiomers of trans-1 showed almost complete mirror images in the CD spectra, where two split Cotton effects (exciton coupling) were observed in the beta-transitions of the naphthyl chromophore at 222 and 235 nm, but no Cotton effect was observed in the stiff-stilbene chromophore at 365 nm. The structures of (R)-10 and trans-(R,R)-1 were confirmed by X-ray structural analysis. The optimized structure of cis-1 by MO calculations has a wide chiral cavity of 7-8 A in diameter, whereas trans-1 cannot form an intramolecular cavity based on the X-ray data. Irradiation of (R,R)-trans-1 with black light (lambda = 365 nm) in CH3CN or benzene at 23 degrees C led to the conversion to the corresponding cis-isomer, as was monitored by 1H NMR, UV-vis, and CD spectra. At the photostationary state, the cis-1/trans-1 ratio was 86/14 in benzene or 75/25 in CH3CN. On the other hand, irradiation of the cis-1/trans-1 (75/25) mixture in CH3CN with an ultra-high-pressure Hg lamp at 23 degrees C (lambda = 410 nm) led to the photostationary state, where the cis-1/trans-1 ratio was estimated to be 9/91 on the basis of the 1H NMR spectra. The cis-trans and trans-cis interconversions could be repeated 10 times without decomposition of the C=C double bond. Thus, a new type of photoswitchable molecule has been developed, and trans-1 and cis-1 were quite durable under irradiation conditions. The guest binding properties of the BINOL moieties of trans- and cis-(R,R)-1 with F-, Cl-, and H2PO4- were examined by 1H NMR titration in CDCl3. Similar interaction with F- and Cl- was observed in trans-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F

Effect of incremental levels of sunflower-seed oil in the diet on ruminal lipid metabolism in lactating cows.

PubMed

Shingfield, K J; Ahvenjärvi, S; Toivonen, V; Vanhatalo, A; Huhtanen, P; Griinari, J M

2008-05-01

Based on the potential benefits of cis-9, trans-11-conjugated linoleic acid (CLA) for human health there is interest in developing sustainable nutritional strategies for enhancing the concentration of this fatty acid in ruminant-derived foods. Most evidence to date suggests that endogenous synthesis is the major source of cis-9, trans-11 in milk fat and ruminal outflow is limited and largely independent of dietary 18 : 2n-6 supply. Four lactating cows fitted with a rumen cannula were used in a 4 x 4 Latin square with 14 d experimental periods to examine the effects of sunflower-seed oil (SFO) as a source of 18 : 2n-6 on ruminal lipid metabolism. Cows were offered grass silage-based diets supplemented with 0, 250, 500 or 750 g SFO/d. Supplements of SFO had no effect on DM intake, milk fat or protein secretion, but increased linearly (P < 0.01) milk yield and milk lactose output and shifted (P < 0.001) rumen fermentation towards propionate at the expense of acetate. SFO supplements increased linearly (P < 0.05) the flow of 18 : 0, 18 : 1, 18 : 2n-6 and total CLA at the omasum and enhanced ruminal cis-9-18 : 1, 18 : 2n-6 and 18 : 3n-3 metabolism. Flows of all-trans- (Delta4-16) and cis- (Delta9-16) 18 : 1 isomers were elevated, while increases in ruminal CLA outflow were confined to trans-8, trans-10 and geometric 9,11 and 10,12 isomers. It is concluded that supplementing grass silage-based diets with plant oils rich in 18 : 2n-6 enhances ruminal outflow of trans-11-18 : 1 and cis-9, trans-11-CLA in lactating cows.

Biosynthesis of cis,cis-muconic acid and its aromatic precursors, catechol and protocatechuic acid, from renewable feedstocks by Saccharomyces cerevisiae.

PubMed

Weber, Christian; Brückner, Christine; Weinreb, Sheila; Lehr, Claudia; Essl, Christine; Boles, Eckhard

2012-12-01

Adipic acid is a high-value compound used primarily as a precursor for the synthesis of nylon, coatings, and plastics. Today it is produced mainly in chemical processes from petrochemicals like benzene. Because of the strong environmental impact of the production processes and the dependence on fossil resources, biotechnological production processes would provide an interesting alternative. Here we describe the first engineered Saccharomyces cerevisiae strain expressing a heterologous biosynthetic pathway converting the intermediate 3-dehydroshikimate of the aromatic amino acid biosynthesis pathway via protocatechuic acid and catechol into cis,cis-muconic acid, which can be chemically dehydrogenated to adipic acid. The pathway consists of three heterologous microbial enzymes, 3-dehydroshikimate dehydratase, protocatechuic acid decarboxylase composed of three different subunits, and catechol 1,2-dioxygenase. For each heterologous reaction step, we analyzed several potential candidates for their expression and activity in yeast to compose a functional cis,cis-muconic acid synthesis pathway. Carbon flow into the heterologous pathway was optimized by increasing the flux through selected steps of the common aromatic amino acid biosynthesis pathway and by blocking the conversion of 3-dehydroshikimate into shikimate. The recombinant yeast cells finally produced about 1.56 mg/liter cis,cis-muconic acid.

Proton affinity of diastereoisomers of modified prolines using the kinetic method and density functional theory calculations: role of the cis/trans substituent on the endo/exo ring conformation.

PubMed

Mezzache, S; Pepe, C; Karoyan, P; Fournier, F; Tabet, J-C

2005-01-01

The proton affinity (PA) of cis/trans-3-prolinoleucines and cis/trans-3-prolinoglutamic acids have been studied by the kinetic method and density functional theory (DFT) calculations. Several conformations of the neutral and the protonated modified prolines, in particular the endo and exo ring conformations, were analyzed with respect to their contribution to the PA values. When the substituent is an alkyl, both the diastereoisomers have the same PA value. However, the PA values for the diastereoisomers are different when the substituted chain contains functional groups (e.g. a carboxyl group). This variation in PA values could be attributed to the existence of intramolecular hydrogen bonds. Copyright (c) 2005 John Wiley & Sons, Ltd.

Comparison of Two Derivatization Methods for the Analysis of Fatty Acids and Trans Fatty Acids in Bakery Products Using Gas Chromatography

PubMed Central

Salimon, Jumat; Omar, Talal A.; Salih, Nadia

2014-01-01

Two different procedures for the methylation of fatty acids (FAs) and trans fatty acids (TFAs) in food fats were compared using gas chromatography (GC-FID). The base-catalyzed followed by an acid-catalyzed method (KOCH3/HCl) and the base-catalyzed followed by (trimethylsilyl)diazomethane (TMS–DM) method were used to prepare FA methyl esters (FAMEs) from lipids extracted from food products. In general, both methods were suitable for the determination of cis/trans FAs. The correlation coefficients (r) between the methods were relatively small (ranging from 0.86 to 0.99) and had a high level of agreement for the most abundant FAs. The significant differences (P = 0.05) can be observed for unsaturated FAs (UFAs), specifically for TFAs. The results from the KOCH3/HCl method showed the lowest recovery values (%R) and higher variation (from 84% to 112%), especially for UFAs. The TMS-DM method had higher R values, less variation (from 90% to 106%), and more balance between variation and %RSD values in intraday and interday measurements (less than 4% and 6%, resp.) than the KOCH3/HCl method, except for C12:0, C14:0, and C18:0. Nevertheless, the KOCH3/HCl method required shorter time and was less expensive than the TMS-DM method which is more convenient for an accurate and thorough analysis of rich cis/trans UFA samples. PMID:24719581

Comparison of two derivatization methods for the analysis of fatty acids and trans fatty acids in bakery products using gas chromatography.

PubMed

Salimon, Jumat; Omar, Talal A; Salih, Nadia

2014-01-01

Two different procedures for the methylation of fatty acids (FAs) and trans fatty acids (TFAs) in food fats were compared using gas chromatography (GC-FID). The base-catalyzed followed by an acid-catalyzed method (KOCH3/HCl) and the base-catalyzed followed by (trimethylsilyl)diazomethane (TMS-DM) method were used to prepare FA methyl esters (FAMEs) from lipids extracted from food products. In general, both methods were suitable for the determination of cis/trans FAs. The correlation coefficients (r) between the methods were relatively small (ranging from 0.86 to 0.99) and had a high level of agreement for the most abundant FAs. The significant differences (P = 0.05) can be observed for unsaturated FAs (UFAs), specifically for TFAs. The results from the KOCH3/HCl method showed the lowest recovery values (%R) and higher variation (from 84% to 112%), especially for UFAs. The TMS-DM method had higher R values, less variation (from 90% to 106%), and more balance between variation and %RSD values in intraday and interday measurements (less than 4% and 6%, resp.) than the KOCH3/HCl method, except for C12:0, C14:0, and C18:0. Nevertheless, the KOCH3/HCl method required shorter time and was less expensive than the TMS-DM method which is more convenient for an accurate and thorough analysis of rich cis/trans UFA samples.

The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

PubMed

Laaksovirta, S; Rajala, P; Nurmi, M; Tammela, T L; Laato, M

1999-01-01

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells

PubMed Central

Armstrong, J L; Ruiz, M; Boddy, A V; Redfern, C P F; Pearson, A D J; Veal, G J

2005-01-01

Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 μM) or R116010 (1 or 10 μM) in combination with either 10 μM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma. PMID:15714209

Trichoplax adhaerens reveals a network of nuclear receptors sensitive to 9-cis-retinoic acid at the base of metazoan evolution

PubMed Central

Novotný, Jan Philipp; Chughtai, Ahmed Ali; Kostrouchová, Markéta; Kostrouchová, Veronika; Kostrouch, David; Kaššák, Filip; Kaňa, Radek; Schierwater, Bernd; Kostrouchová, Marta

2017-01-01

Trichoplax adhaerens, the only known species of Placozoa is likely to be closely related to an early metazoan that preceded branching of Cnidaria and Bilateria. This animal species is surprisingly well adapted to free life in the World Ocean inhabiting tidal costal zones of oceans and seas with warm to moderate temperatures and shallow waters. The genome of T. adhaerens (sp. Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues. In the case of RXR, the sequence identity to human RXR alpha reaches 81% in the DNA binding domain and 70% in the ligand binding domain. We show that T. adhaerens RXR (TaRXR) binds 9-cis retinoic acid (9-cis-RA) with high affinity, as well as high specificity and that exposure of T. adhaerens to 9-cis-RA regulates the expression of the putative T. adhaerens orthologue of vertebrate L-malate-NADP+ oxidoreductase (EC 1.1.1.40) which in vertebrates is regulated by a heterodimer of RXR and thyroid hormone receptor. Treatment by 9-cis-RA alters the relative expression profile of T. adhaerens nuclear receptors, suggesting the existence of natural ligands. Keeping with this, algal food composition has a profound effect on T. adhaerens growth and appearance. We show that nanomolar concentrations of 9-cis-RA interfere with T. adhaerens growth response to specific algal food and causes growth arrest. Our results uncover an endocrine-like network of nuclear receptors sensitive to 9-cis-RA in T. adhaerens and support the existence of a ligand-sensitive network of nuclear receptors at the base of metazoan evolution. PMID:28975052

Effects of proline cis-trans isomerization on TB domain secondary structure.

PubMed Central

Yuan, X.; Werner, J. M.; Knott, V.; Handford, P. A.; Campbell, I. D.; Downing, K.

1998-01-01

The transforming growth factor beta (TGF-beta) binding protein-like (TB) domain is found principally in proteins localized to extracellular matrix fibrils, including human fibrillin-1, the defective protein in the Marfan syndrome. Analysis of the nuclear magnetic resonance (NMR) data for the sixth TB module from human fibrillin-1 has revealed the existence of two stable conformers that differ in the isomerization states of two proline residues. Unusually, the two isoforms do not readily interconvert and are stable on the time scale of milliseconds. We have computed independent structures of the major and minor conformers of TB6 to assess how the domain fold adjusts to incorporate alternatively cis- or trans-prolines. Based on previous observations, it has been suggested that multiple conformers can only be accommodated in flexible regions of protein structure. In contrast, P22, which exists in trans in the major form and cis in the minor form of TB6, is in a rigid region of the domain, which is confirmed by backbone dynamics measurements. Overall, the structures of the major and minor conformers are similar. However, the secondary structure topologies of the two forms differ as a direct consequence of the changes in proline conformation. PMID:9792099

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

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

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductasemore » 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.« less

[The prevalence of cis-9-hexadecenoic acid is a specific feature of the fatty acid profile of zygomycetes from the order Kickxellales].

PubMed

Konova, I V; Kochkina, G A; Galanina, L A

2005-01-01

The fatty acid profiles of zygomycetes from the family Kickxellaceae of the order Kickxellales were studied with reference to the species Kicksella alabastrina of the key genus Kicksella of the family and the species Linderina pennispora. When synthesized de novo, the lipids of these species show the prevalence of cis-9-hexadecenoic acid. This trait is stable, does not depend on cultivation conditions, and can, therefore, be considered as a specific chemotaxonomic characteristic of fungi from the order Kickxellales. The fatty acid profiles of the two fungi under study are similar to that of sea buckthorn oil.

Effects of butter naturally enriched with conjugated linoleic acid and vaccenic acid on blood lipids and LDL particle size in growing pigs

PubMed Central

Haug, Anna; Sjøgren, Per; Hølland, Nina; Müller, Hanne; Kjos, Nils P; Taugbøl, Ole; Fjerdingby, Nina; Biong, Anne S; Selmer-Olsen, Eirik; Harstad, Odd M

2008-01-01

Background Cow milk is a natural source of the cis 9, trans 11 isomer of conjugated linoleic acid (c9,t11-CLA) and trans vaccenic acid (VA). These fatty acids may be considered as functional foods, and the concentration in milk can be increased by e.g. sunflower oil supplementation to the dairy cow feed. The objective of this study was to compare the effects of regular butter with a special butter naturally enriched in c9,t11-CLA and VA on plasma lipids in female growing pigs. The experimental period lasted for three weeks and the two diets provided daily either 5.0 g c9,t11-CLA plus 15.1 g VA or 1.3 g c9,t11-CLA plus 3.6 g VA. Results The serum concentrations of c9,t11-CLA, VA and alpha-linolenic acid were increased and myristic (14:0) and palmitic acid (16:0) were reduced in the pigs fed the CLA+VA-rich butter-diet compared to regular butter, but no differences in plasma concentrations of triacylglycerol, cholesterol, HDL-cholesterol, LDL-cholesterol, LDL particle size distribution or total cholesterol/HDL cholesterol were observed among the two dietary treatment groups. Conclusion Growing pigs fed diets containing butter naturally enriched in about 20 g c9,t11-CLA plus VA daily for three weeks, had increased serum concentrations of alpha-linolenic acid and decreased myristic and palmitic acid compared to pigs fed regular butter, implying a potential benefit of the CLA+VA butter on serum fatty acid composition. Butter enriched in CLA+VA does not appear to have significant effect on the plasma lipoprotein profile in pigs. PMID:18759970

Diet-induced milk fat depression is associated with alterations in ruminal biohydrogenation pathways and formation of novel fatty acid intermediates in lactating cows.

PubMed

Ventto, Laura; Leskinen, Heidi; Kairenius, Piia; Stefański, Tomasz; Bayat, Ali R; Vilkki, Johanna; Shingfield, Kevin J

2017-02-01

The biohydrogenation theory of milk fat depression (MFD) attributes decreases in milk fat in cows to the formation of specific fatty acids (FA) in the rumen. Trans-10, cis-12-CLA is the only biohydrogenation intermediate known to inhibit milk fat synthesis, but it is uncertain if increased ruminal synthesis is the sole explanation of MFD. Four lactating cows were used in a 4×4 Latin square with a 2×2 factorial arrangement of treatments and 35-d experimental periods to evaluate the effect of diets formulated to cause differences in ruminal lipid metabolism and milk fat synthesis on the flow of FA and dimethyl acetal at the omasum. Treatments comprised total mixed rations based on grass silage with a forage:concentrate ratio of 35:65 or 65:35 containing 0 or 50 g/kg sunflower oil (SO). Supplementing the high-concentrate diet with SO lowered milk fat synthesis from -20·2 to -31·9 % relative to other treatments. Decreases in milk fat were accompanied by alterations in ruminal biohydrogenation favouring the trans-10 pathway and an increase in the formation of specific intermediates including trans-4 to trans-10-18 : 1, trans-8, trans-10-CLA, trans-9, cis-11-CLA and trans-10, cis-15-18 : 2. Flow of trans-10, cis-12-CLA at the omasum was greater on high- than low-concentrate diets but unaffected by SO. In conclusion, ruminal trans-10, cis-12-CLA formation was not increased on a diet causing MFD suggesting that other biohydrogenation intermediates or additional mechanisms contribute to the regulation of fat synthesis in the bovine mammary gland.

Ensemble of Transition State Structures for the Cis-Trans Isomerization of N-Methylacetamide

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

Mantz, Yves A.; Branduardi, Davide; Bussi, Giovanni

2009-09-17

The cis-trans isomerization of N-methylacetamide (NMA), a model peptidic fragment, is studied theoretically in vacuo and in explicit water solvent at 300 K using the metadynamics technique. The computed cis-trans free energy difference is very similar for NMA(g) and NMA(aq), in agreement with experimental measurements of population ratios and theoretical studies at 0 K. By exploiting the flexibility in the definition of a pair of recently introduced collective variables (Branduardi, D.; Gervasio, F. L.; Parrinello, M. J. Chem. Phys. 2007, 126, 054103), an ensemble of transition state structures is generated at finite temperature for both NMA(g) and NMA(aq), as verifiedmore » by computing committor distribution functions. Ensemble members of NMA(g) are shown to have correlated values of the backbone dihedral angle and a second dihedral angle involving the amide hydrogen atom. The dynamical character of these structures is preserved in the presence of solvent, whose influence on the committor functions can be modeled using effective friction/noise terms.« less

Mechanistic insights into Pin1 peptidyl-prolyl cis-trans isomerization from umbrella sampling simulations.

PubMed

Di Martino, Giovanni Paolo; Masetti, Matteo; Cavalli, Andrea; Recanatini, Maurizio

2014-11-01

The peptidyl-proyl isomerase Pin1 plays a key role in the regulation of phospho(p)-Ser/Thr-Pro proteins, acting as a molecular timer of the cell cycle. After recognition of these motifs, Pin1 catalyzes the rapid cis-trans isomerization of proline amide bonds of substrates, contributing to maintain the equilibrium between the two conformations. Although a great interest has arisen on this enzyme, its catalytic mechanism has long been debated. Here, the cis-trans isomerization of a model peptide system was investigated by means of umbrella sampling simulations in the Pin1-bound and unbound states. We obtained free energy barriers consistent with experimental data, and identified several enzymatic features directly linked to the acceleration of the prolyl bond isomerization. In particular, an enhanced autocatalysis, the stabilization of perturbed ground state conformations, and the substrate binding in a procatalytic conformation were found as main contributions to explain the lowering of the isomerization free energy barrier. © 2014 Wiley Periodicals, Inc.

[Trans-fatty acids--effects on coronary heart disease].

PubMed

Karbowska, Joanna; Kochan, Zdzisław

2011-07-01

Trans-fatty acids (TFA) are formed during the industrial process of hydrogenation of vegetable oils. The consumption of hydrogenated fats has increased significantly over the last few decades. In Poland, the average daily intake of TFA for adults was estimated to be 2.8 to 6.9 g; which greatly exceeds the recommended daily maximum of 2 g/day (less than 1% of total energy intake). Increasing trans-fatty acid intake has detrimental effects on the lipid profile: TFA raise total cholesterol, LDL-cholesterol and triglyceride concentrations, and decrease HDL-cholesterol levels. Moreover, dietary trans-fatty acids may increase plasma levels of lipoprotein (a) and biomarkers of inflammation and endothelial dysfunction. Several studies have demonstrated that a high intake of TFA is associated with an increased risk of coronary heart disease. In addition, TFA consumption has been implicated as an independent risk factor for sudden cardiac arrest. It is therefore necessary to reduce the intake of hydrogenated fats rich in trans-fatty acids in order to minimize the adverse effects of TFA on health.

Occurrence ofCis-6-hexadecenoic acid as the major component ofThunbergia alata seed oil.

PubMed

Spencer, G F; Kleiman, R; Miller, R W; Earle, F R

1971-10-01

An unusual series of monoenoic fatty acids constitutes about 85% of the total acids in seed oil fromThunbergia alata. The major component in the oil,cis-6-hexadecenoic acid (82%), is accompanied by the homologous 4-tetradecenoic (ca. 0.2%) and 8-octadecenoic (1.8%) acids. Another homologous series is represented by 5-tetradecenoic (ca. 0.2%), 7-hexadecenoic (1.8%) and the familiar 9-octadecenoic (4.4%) acids. Traces (<0.1%) of three other acids, 6-tetradecenoic and 10- and 11-octadecenoic, are also present along with palmitic (5.8%), stearic (0.6%) and linoleic (2.2%) acids. Some of the monoenoic acids have not previously been known to occur in seed oils.

Steric analysis of epoxyalcohol and trihydroxy derivatives of 9-hydroperoxy-linoleic acid from hematin and enzymatic synthesis

PubMed Central

Thomas, Christopher P.; Boeglin, William E.; Garcia-Diaz, Yoel; O’Donnell, Valerie B.; Brash, Alan R.

2013-01-01

We characterize the allylic epoxyalcohols and their trihydroxy hydrolysis products generated from 9R- and 9S-hydroperoxy-octadecenoic acid (HPODE) under non-enzymatic conditions, reaction with hematin and subsequent acid hydrolysis, and enzymatic conditions, incubation with Beta vulgaris containing a hydroperoxide isomerase and epoxide hydrolase. The products were resolved by HPLC and the regio and stereo-chemistry of the transformations were determined through a combination of 1H NMR and GC-MS analysis of dimethoxypropane derivatives. Four trihydroxy isomers were identified upon mild acid hydrolysis of 9S,10S-trans-epoxy-11E-13S-hydroxyoctadecenoate: 9S,10R,13S, 9S,12R,13S, 9S,10S,13S and 9S,12S,13S-trihydroxy-octadecenoic acids, in the ratio 40:26:22:12. We also identified a prominent -ketol rearrangement product from the hydrolysis as mainly the 9-hydroxy-10E-13-oxo isomer. Short incubation (5 min) of 9R- and 9S-HPODE with Beta vulgaris extract yielded the 9R- and 9S-hydroxy-10E-12R,13S-cis-epoxy products respectively. Longer incubation (60 min) gave one specific hydrolysis product via epoxide hydrolase, the 9R/S,12S,13S-trihydroxyoctadecenoate. These studies provide a practical approach for the isolation and characterization of allylic epoxy alcohol and trihydroxy products using a combination of HPLC, GC-MS and 1H NMR. PMID:23352713

Short communication: Discrimination between retail bovine milks with different fat contents using chemometrics and fatty acid profiling.

PubMed

Vargas-Bello-Pérez, Einar; Toro-Mujica, Paula; Enriquez-Hidalgo, Daniel; Fellenberg, María Angélica; Gómez-Cortés, Pilar

2017-06-01

We used a multivariate chemometric approach to differentiate or associate retail bovine milks with different fat contents and non-dairy beverages, using fatty acid profiles and statistical analysis. We collected samples of bovine milk (whole, semi-skim, and skim; n = 62) and non-dairy beverages (n = 27), and we analyzed them using gas-liquid chromatography. Principal component analysis of the fatty acid data yielded 3 significant principal components, which accounted for 72% of the total variance in the data set. Principal component 1 was related to saturated fatty acids (C4:0, C6:0, C8:0, C12:0, C14:0, C17:0, and C18:0) and monounsaturated fatty acids (C14:1 cis-9, C16:1 cis-9, C17:1 cis-9, and C18:1 trans-11); whole milk samples were clearly differentiated from the rest using this principal component. Principal component 2 differentiated semi-skim milk samples by n-3 fatty acid content (C20:3n-3, C20:5n-3, and C22:6n-3). Principal component 3 was related to C18:2 trans-9,trans-12 and C20:4n-6, and its lower scores were observed in skim milk and non-dairy beverages. A cluster analysis yielded 3 groups: group 1 consisted of only whole milk samples, group 2 was represented mainly by semi-skim milks, and group 3 included skim milk and non-dairy beverages. Overall, the present study showed that a multivariate chemometric approach is a useful tool for differentiating or associating retail bovine milks and non-dairy beverages using their fatty acid profile. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Molecular cloning and expression profile of ß-ketoacyl-acp synthase gene from tung tree (Vernicia fordii Hemsl.)

USDA-ARS?s Scientific Manuscript database

Tung tree (Vernicia fordii) is an important woody oil tree. Tung tree seeds contain 50-60% oil with approximately 80 mole a-eleostearic acid (9cis, 11trans, 13trans octadecatrienoic acid). Fatty acid synthesis is catalyzed by the concerted action of acetyl-CoA carboxylase and fatty acid synthase, a ...

Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men

PubMed Central

Lisulo, M M; Kapulu, M C; Banda, R; Sinkala, E; Kayamba, V; Sianongo, S; Kelly, P

2014-01-01

There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of α4β7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10 nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3 h after 10 mg ATRA. We then evaluated the effect of 10 mg ATRA given 1 h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] Cmax was 26·2 (11·7–39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P = 0·02) and protein (P = 0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant. PMID:24237035

Thermodynamic and kinetic data for adduct formation, cis-trans isomerization and redox reactions of ML4 complexes: a case study with rhodium- and iridium-tropp complexes in d8, d9 and d10 valence electron configurations (tropp=dibenzotropylidene phosphanes).

PubMed

Breher, Frank; Rüegger, Heinz; Mlakar, Marina; Rudolph, Manfred; Deblon, Stephan; Schönberg, Hartmut; Boulmaâz, Souad; Thomaier, Jörg; Grützmacher, Hansjörg

2004-02-06

The formation of adducts of the square-planar 16-electron complexes trans-[M(tropp(ph))(2)](+) and cis-[M(tropp(ph))(2)](+) (M=Rh, Ir; tropp(Ph)=5-diphenylphosphanyldibenzo[a,d]cycloheptene) with acetonitrile (acn) and Cl(-), and the redox chemistry of these complexes was investigated by various physical methods (NMR and UV-visible spectroscopy, square-wave voltammetry), in order to obtain some fundamental thermodynamic and kinetic data for these systems. A trans/cis isomerization cannot be detected for [M(tropp(ph))(2)](+) in non-coordinating solvents. However, both isomers are connected through equilibria of the type trans-[M(tropp(ph))(2)](+)+L<==>[ML(tropp(ph))(2)](n)<==>cis-[M(tropp(ph))(2)](+)+L, involving five-coordinate intermediates [ML(tropp(ph))(2)](n) (L=acn, n=+1; L=Cl(-), n=0). Values for K(d) (K(f)), that is, the dissociation (formation) equilibrium constant, and k(d) (k(f)), that is, the dissociation (formation) rate constant, were obtained. The formation reactions are fast, especially with the trans isomers (k(f)>1x10(5) m(-1) s(-1)). The reaction with the sterically more hindered cis isomers is at least one order of magnitude slower. The stability of the five-coordinate complexes [ML(tropp(ph))(2)](n) increases with Ir>Rh and Cl(-)>acn. The dissociation reaction has a pronounced influence on the square-wave (SW) voltammograms of trans/cis-[Ir(tropp(ph))(2)](+). With the help of the thermodynamic and kinetic data independently determined by other physical means, these reactions could be simulated and allowed the setting up of a reaction sequence. Examination of the data obtained showed that the trans/cis isomerization is a process with a low activation barrier for the four-coordinate 17-electron complexes [M(tropp(ph))(2)](0) and especially that a disproportionation reaction 2 trans/cis-[M(tropp(ph))(2)](0)-->[M(tropp(ph))(2)](+)+[M(tropp(ph))(2)](-) may be sufficiently fast to mask the true reactivity of the paramagnetic species, which are

Effect of palmitic acid on the mitigation of milk fat depression syndrome caused by trans-10, cis-12-conjugated linoleic acid in grazing dairy cows.

PubMed

Granados-Rivera, Lorenzo Danilo; Hernández-Mendo, Omar; González-Muñoz, Sergio Segundo; Burgueño-Ferreira, Juan Andrés; Mendoza-Martínez, German David; Arriaga-Jordán, Carlos Manuel

2017-12-01

The objective of the study was to evaluate the effect of adding protected palmitic acid (PA) to the ration of grazing dairy cows supplemented with protected conjugated linoleic acid (CLA) on milk production, chemical composition and fat profile. Six cows were used, 3/4 American Swiss × Zebu, under a rotational grazing system in a mixed sward with Cynodon plectostachyus, Brachiaria decumbens and Brachiaria brizantha. Furthermore, each cow received daily 4 kg concentrates and 8 kg sorghum silage, which made up the basal diet. The cows were distributed into three two-cow groups. Three treatments were randomly assigned to the groups, using a cross design: (1) control (basal diet), (2) basal diet + CLA (50 g/d) and (3) basal diet + CLA (50 g/d) + PA (412 g/d). The following variables were evaluated: forage intake, milk production, protein, fat and lactose concentration in milk, and milk fatty acid (FA) profile. There were no differences in forage intake between treatments; however, there were differences in milk production, protein, fat and lactose yield and fat concentration, which increased significantly in group CLA + PA when compared with group CLA. The concentration of FA synthesised de novo was lower when PA was included in the diet. Adding PA to the diet of grazing cows mitigates the milk fat decline caused by including trans-10, cis-12 CLA in the diet.

Trans-cis isomerization of lipophilic dyes probing membrane microviscosity in biological membranes and in live cells.

PubMed

Chmyrov, Volodymyr; Spielmann, Thiemo; Hevekerl, Heike; Widengren, Jerker

2015-06-02

Membrane environment and fluidity can modulate the dynamics and interactions of membrane proteins and can thereby strongly influence the function of cells and organisms in general. In this work, we demonstrate that trans-cis isomerization of lipophilic dyes is a useful parameter to monitor packaging and fluidity of biomembranes. Fluorescence fluctuations, generated by trans-cis isomerization of the thiocarbocyanine dye Merocyanine 540 (MC540), were first analyzed by fluorescence correlation spectroscopy (FCS) in different alcohol solutions. Similar isomerization kinetics of MC540 in lipid vesicles could then also be monitored, and the influence of lipid polarity, membrane curvature, and cholesterol content was investigated. While no influence of membrane curvature and lipid polarity could be observed, a clear decrease in the isomerization rates could be observed with increasing cholesterol contents in the vesicle membranes. Finally, procedures to spatially map photoinduced and thermal isomerization rates on live cells by transient state (TRAST) imaging were established. On the basis of these procedures, MC540 isomerization was studied on live MCF7 cells, and TRAST images of the cells at different temperatures were found to reliably detect differences in the isomerization parameters. Our studies indicate that trans-cis isomerization is a useful parameter for probing membrane dynamics and that the TRAST imaging technique can provide spatial maps of photoinduced isomerization as well as both photoinduced and thermal back-isomerization, resolving differences in local membrane microviscosity in live cells.

Thermal decay of rhodopsin: role of hydrogen bonds in thermal isomerization of 11-cis retinal in the binding site and hydrolysis of protonated Schiff base.

PubMed

Liu, Jian; Liu, Monica Yun; Nguyen, Jennifer B; Bhagat, Aditi; Mooney, Victoria; Yan, Elsa C Y

2009-07-01

Although thermal stability of the G protein-coupled receptor rhodopsin is directly related to its extremely low dark noise level and has recently generated considerable interest, the chemistry behind the thermal decay process of rhodopsin has remained unclear. Using UV-vis spectroscopy and HPLC analysis, we have demonstrated that the thermal decay of rhodopsin involves both hydrolysis of the protonated Schiff base and thermal isomerization of 11-cis to all-trans retinal. Examining the unfolding of rhodopsin by circular dichroism spectroscopy and measuring the rate of thermal isomerization of 11-cis retinal in solution, we conclude that the observed thermal isomerization of 11-cis to all-trans retinal happens when 11-cis retinal is in the binding pocket of rhodopsin. Furthermore, we demonstrate that solvent deuterium isotope effects are involved in the thermal decay process by decreasing the rates of thermal isomerization and hydrolysis, suggesting that the rate-determining step of these processes involves breaking hydrogen bonds. These results provide insight into understanding the critical role of an extensive hydrogen-bonding network on stabilizing the inactive state of rhodopsin and contribute to our current understanding of the low dark noise level of rhodopsin, which enables this specialized protein to function as an extremely sensitive biological light detector. Because similar hydrogen-bonding networks have also been suggested by structural analysis of two other GPCRs, beta1 and beta2 adrenergic receptors, our results could reveal a general role of hydrogen bonds in facilitating GPCR function.

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats.

PubMed

Longhi, Rafael; Almeida, Roberto Farina; Machado, Letiane; Duarte, Maria Marta Medeiros Frescura; Souza, Débora Guerini; Machado, Priscila; de Assis, Adriano Martimbianco; Quincozes-Santos, André; Souza, Diogo Onofre

2017-04-01

Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats. Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed. Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

PubMed

Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

2016-08-01

The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

PubMed Central

Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

2016-01-01

ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome

cis,cis-Muconic acid: separation and catalysis to bio-adipic acid for nylon-6,6 polymerization

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

Vardon, Derek R.; Rorrer, Nicholas A.; Salvachúa, Davinia

cis,cis-Muconic acid is a polyunsaturated dicarboxylic acid that can be produced renewably via the biological conversion of sugars and lignin-derived aromatic compounds. Subsequently, muconic acid can be catalytically converted to adipic acid -- the most commercially significant dicarboxylic acid manufactured from petroleum. Nylon-6,6 is the major industrial application for adipic acid, consuming 85% of market demand; however, high purity adipic acid (99.8%) is required for polymer synthesis. As such, process technologies are needed to effectively separate and catalytically transform biologically derived muconic acid to adipic acid in high purity over stable catalytic materials. To that end, this study: (1) demonstratesmore » bioreactor production of muconate at 34.5 g L-1 in an engineered strain of Pseudomonas putida KT2440, (2) examines the staged recovery of muconic acid from culture media, (3) screens platinum group metals (e.g., Pd, Pt, Rh, Ru) for activity and leaching stability on activated carbon (AC) and silica supports, (4) evaluates the time-on-stream performance of Rh/AC in a trickle bed reactor, and (5) demonstrates the polymerization of bio-adipic acid to nylon-6,6. Separation experiments confirmed AC effectively removed broth color compounds, but subsequent pH/temperature shift crystallization resulted in significant levels of Na, P, K, S and N in the crystallized product. Ethanol dissolution of muconic acid precipitated bulk salts, achieving a purity of 99.8%. Batch catalysis screening reactions determined that Rh and Pd were both highly active compared to Pt and Ru, but Pd leached significantly (1-9%) from both AC and silica supports. Testing of Rh/AC in a continuous trickle bed reactor for 100 h confirmed stable performance after 24 h, although organic adsorption resulted in reduced steady-state activity. Lastly, polymerization of bio-adipic acid with hexamethyldiamine produced nylon-6,6 with comparable properties to its petrochemical

Thiazolidine peracetates: carbohydrate derivatives that readily assign cis-, trans-2,3- monosaccharides by GC/MS analysis

USDA-ARS?s Scientific Manuscript database

A novel group of carbohydrate derivatives is described that uniquely assign cis/trans-2,3 aldose stereoisomers at low nanomolar concentrations. Aldopentoses or aldohexoses, or component aldoses from hydrolysis of polysaccharides or oligosaccharides, react with cysteamine in pyridine to give quantita...

Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the Interpretation of Lipidomic Profiles

PubMed Central

Sansone, Anna; Tolika, Evanthia; Louka, Maria; Sunda, Valentina; Deplano, Simone; Melchiorre, Michele; Anagnostopoulos, Dimitrios; Chatgilialoglu, Chryssostomos; Formisano, Cesare; Di Micco, Rosa; Faraone Mennella, Maria Rosaria; Ferreri, Carla

2016-01-01

Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the

Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the Interpretation of Lipidomic Profiles.

PubMed

Sansone, Anna; Tolika, Evanthia; Louka, Maria; Sunda, Valentina; Deplano, Simone; Melchiorre, Michele; Anagnostopoulos, Dimitrios; Chatgilialoglu, Chryssostomos; Formisano, Cesare; Di Micco, Rosa; Faraone Mennella, Maria Rosaria; Ferreri, Carla

2016-01-01

Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the

Photoionization and trans-to-cis isomerization of β-cyclodextrin-encapsulated azobenzene induced by two-color two-laser-pulse excitation.

PubMed

Takeshita, Tatsuya; Hara, Michihiro

2018-03-15

Azobenzene (1) and the complex resulting from the incorporation of 1 with cyclodextrin (1/CD) are attractive for light-driven applications such as micromachining and chemical biology tools. The highly sensitive photoresponse of 1 is crucial for light-driven applications containing both 1 and 1/CD to reach their full potential. In this study, we investigated the photoionization and trans-to-cis isomerization of 1/CD induced by one- and two-color two-laser pulse excitation. Photoionization of 1/CD, which was induced by stepwise two-photon absorption, was observed using laser pulse excitation at 266nm. Additionally, simultaneous irradiation with 266 and 532nm laser pulses increased the trans-to-cis isomerization yield (Υ t→c ) by 27%. It was concluded that the increase in Υ t→c was caused by the occurrence of trans-to-cis isomerization in the higher-energy singlet state (S n ), which was reached by S 1 →S n transition induced by laser pulse excitation at 532nm. The results of this study are potentially applicable in light-driven applications such as micromachining and chemical biology tools. Copyright © 2018 Elsevier B.V. All rights reserved.

cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration

PubMed Central

Sato, Shinya

2016-01-01

Key points This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment.We report that the retina visual cycle provides cones exclusively with 11‐cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11‐cis‐specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells.Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark‐adapt in the retina following a bleach and to use exogenous 9‐cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone‐specific and pigment‐independent.Our results show that the retina produces 11‐cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. Abstract Chromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase‐1, the putative all‐trans retinol isomerase in Müller cells, appears to be 9‐cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11‐cis retinal. Here, we used the different absorption spectra of 9‐cis and 11‐cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark‐adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark‐adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11‐cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a

cis-1,2-Dichloroethylene

Integrated Risk Information System (IRIS)

EPA / 635 / R - 09 / 006 F www.epa.gov / iris TOXICOLOGICAL REVIEW OF cis - 1,2 - DICHLOROETHYLENE and trans - 1,2 - DICHLOROETHYLENE ( CAS Nos . cis : 156 - 59 - 2 ; trans : 156 - 60 - 5 ; mixture : 540 - 59 - 0 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS )

[Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma].

PubMed

Adamczewski, Zbigniew; Makarewicz, Jacek; Mikosiński, Sławomir; Knapska-Kucharska, Małgorzata; Gunerska-Szadkowska, Anna; Oszukowska, Lidia; Karwowska, Anzelmina; Lewiński, Andrzej

2006-01-01

The loss of iodine uptake by differentiated thyroid carcinoma (DTC) cells is a major therapeutic problem especially in patients with nonsurgical metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted to retain iodine uptake as a result of redifferentiation (influence by retinoic acid receptors present in DTC cells). Between 1999 and 2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were treated twice - 13 treatment cycles in total). Side effects in skin and mucous membranes were observed in all the patients, however, their intensity did not require termination of the therapy. Increase of iodine uptake was observed in 5 patients (45%). Decreased Tg concentration was observed in 9 patients. In that group, increased (131)I uptake was observed in 4 patients with distant metastases. All determinations of Tg concentrations were carried out under TSH stimulation. 13-cis-retinoic acid causes an increase of radioiodine uptake in around half of treated patients, however, the follow-up of these patients indicates that this increase does not result in either full remission or even stabilisation of neoplastic disease. The possibility should be considered to use cis-retinoic acid as an independent therapeutic approach in patients with radioiodine non-avid foci of thyroid carcinoma especially those showing high expression of RARb and RXRg receptors.

Detection of 11 beta-hydroxysteroid dehydrogenase type 1, the glucocorticoid and mineralocorticoid receptor in various adipose tissue depots of dairy cows supplemented with conjugated linoleic acids.

PubMed

Friedauer, K; Dänicke, S; Schulz, K; Sauerwein, H; Häussler, S

2015-10-01

Early lactating cows mobilize adipose tissue (AT) to provide energy for milk yield and maintenance and are susceptible to metabolic disorders and impaired immune response. Conjugated linoleic acids (CLA), mainly the trans-10, cis-12 isomer, reduce milk fat synthesis and may attenuate negative energy balance. Circulating glucocorticoids (GC) are increased during parturition in dairy cows and mediate differentiating and anti-inflammatory effects via glucocorticoid (GR) and mineralocorticoid receptors (MR) in the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). Activated GC are the main ligands for both receptors in AT; therefore, we hypothesized that tissue-specific GC metabolism is effected by varying amounts of GR, MR and 11βHSD1 and/or their localization within AT depots. Furthermore, the lipolytic and antilipogenic effects of CLA might influence the GC/GR/MR system in AT. Therefore, we aimed to localize GR and MR as well as the expression pattern and activity of 11βHSD1 in different AT depots during early lactation in dairy cows and to identify potential effects of CLA. Primiparous German Holstein cows were divided into a control (CON) and a CLA group. From day 1 post-partum (p.p.) until sample collection, the CLA group was fed with 100 g/d CLA (contains 10 g each of the cis-9, trans-11 and the trans-10, cis-12-CLA isomers). CON cows (n = 5 each) were slaughtered on day 1, 42 and 105 p.p., while CLA cows (n = 5 each) were slaughtered on day 42 and 105 p.p. Subcutaneous fat from tailhead, withers and sternum, and visceral fat from omental, mesenteric and retroperitoneal depots were sampled. The localization of GR and 11βHSD1 in mature adipocytes - being already differentiated - indicates that GC promote other effects via GR than differentiation. Moreover, MR were observed in the stromal vascular cell fraction and positively related to the pre-adipocyte marker Pref-1. However, only marginal CLA effects were observed in this study

Comparison of the Photodesorption Activities of cis-Butene, trans-Butene and Isobutene on the Rutile TiO 2(110) Surface

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

Henderson, Michael A.

2013-10-17

The chemical and photochemical properties of three butene molecules (cis-butene, trans-butene and isobutene) were explored on the clean rutile TiO 2(110) surface using temperature programmed desorption (TPD) and photon simulated desorption (PSD). At the low coverage limit, trans-butene was the most strongly bound butene on the TiO 2(110) surface, desorbing at ~ 210 K, however increased intermolecular repulsions between trans-butene molecules at higher coverage diminished its binding. Both cis-butene and isobutene saturated the first layer on TiO 2(110) at a coverage of ~0.50 ML in a single TPD feature at 184 and 192 K, respectively. In contrast, the maximum coveragemore » that trans-butene could achieve in its 210 K peak was ~1/3 ML, with higher coverages resulting a low temperature desorption at ~137 K. Coverages of these molecules above 0.50 ML resulted in population of second layer and multilayer states. The instability of trans-butene at a coverage of 0.5 ML on the surface was linked to the inversion center in its symmetry. In the absence of coadsorbed oxygen, the primary photochemical pathway of each butene molecule on TiO 2(110) was photodesorption. The photoactivities of these molecules on TiO 2(110) at an initial coverage of 0.50 ML followed the trend: isobutene > cis-butene > trans-butene. In contrast, the photoactivities of low coverages of cis-butene and trans-butene exceeded those measured at 0.50 ML. These data suggest that intermolecular interactions (repulsions) play a significant role in diminishing the photoactivities of weakly bound molecules on TiO 2 photocatalysts. Work reported here was supported by the U.S. Department of Energy, Office of Basic Energy Science, Division of Chemical Sciences, Geosciences, and Biosciences, and performed in the Williams R. Wiley Environmental Molecular Science Laboratory (EMSL), a Department of Energy user facility funded by the Office of Biological and Environmental Research. Pacific Northwest National

Effects of cytotoxic cis- and trans-diammine monochlorido platinum(II) complexes on selenium-dependent redox enzymes and DNA.

PubMed

Lemmerhirt, Heidi; Behnisch, Steven; Bodtke, Anja; Lillig, Christopher H; Pazderova, Lucia; Kasparkova, Jana; Brabec, Viktor; Bednarski, Patrick J

2018-01-01

Here we present the preparation of 14 pairs of cis- and trans-diammine monochlorido platinum(II) complexes, coordinated to heterocycles (i.e., imidazole, 2-methylimidazole and pyrazole) and linked to various acylhydrazones, which were designed as potential inhibitors of the selenium-dependent enzymes glutathione peroxidase 1 (GPx-1) and thioredoxin reductase 1 (TrxR-1). However, no inhibition of bovine GPx-1 and only weak inhibition of murine TrxR-1 was observed in in vitro assays. Nonetheless, the cis configured diammine monochlorido Pt(II) complexes exhibited cytotoxic and apoptotic properties on various human cancer cell lines, whereas the trans configured complexes generally showed weaker potency with a few exceptions. On the other hand, the trans complexes were generally more likely to lack cross-resistance to cisplatin than the cis analogues. Platinum was found bound to the nuclear DNA of cancer cells treated with representative Pt complexes, suggesting that DNA might be a possible target. Thus, detailed in vitro binding experiments with DNA were conducted. Interactions of the compounds with calf thymus DNA were investigated, including Pt binding kinetics, circular dichroism (CD) spectral changes, changes in DNA melting temperatures, unwinding of supercoiled plasmids and ethidium bromide displacement in DNA. The CD results indicate that the most active cis configured pyrazole-derived complex causes unique structural changes in the DNA compared to the other complexes as well as to those caused by cisplatin, suggesting a denaturation of the DNA structure. This may be important for the antiproliferative activity of this compound in the cancer cells. Copyright © 2017. Published by Elsevier Inc.

Micro liquid chromatography-mass spectrometry with direct liquid introduction used for separation and quantitation of all-trans- and 13-cis-retinoic acids and their 4-oxo metabolites in human plasma.

PubMed

Ranalder, U B; Lausecker, B B; Huselton, C

1993-07-23

The separation and quantitation of the pentafluorobenzyl derivatives of all-trans- and 13-cis-retinoic acids and their 4-oxo metabolites in human plasma on micro high-performance liquid chromatographic columns (0.32 mm I.D.) is described. The column outlet was directly coupled to the source of a quadrupole mass spectrometer via a simple SFC-frit interface. Negative ion chemical ionization conditions were obtained by coaxial introduction of ammonia as a reagent gas. A signal-to-noise ratio well above 3 was obtained for 1 pg of each analyte injected. The limit of quantitation calculated from spiked biological plasma extracts was 0.3 ng/ml.

Communication: An accurate calculation of the S 1 C 2H 2 cis-trans isomerization barrier height

DOE PAGES

Baraban, Joshua H.; Matthews, Devin A.; Stanton, John F.

2016-03-16

In this study, a high level ab initio calculation of the cis-trans isomerization barrier height in the first excited singlet electronic state of acetylene is found to agree very well with a recent experimental determination.

Biochemical Properties of Purified Human Retinol Dehydrogenase 12 (RDH12): Catalytic Efficiency toward Retinoids and C9 Aldehydes and Effects of Cellular Retinol-Binding Protein Type I (CRBPI) and Cellular Retinaldehyde-Binding Protein (CRALBP) on the Oxidation and Reduction of Retinoids†

PubMed Central

Belyaeva, Olga V.; Korkina, Olga V.; Stetsenko, Anton V.; Kim, Tom; Nelson, Peter S.; Kedishvili, Natalia Y.

2008-01-01

Retinol dehydrogenase 12 (RDH12) is a novel member of the short-chain dehydrogenase/reductase superfamily of proteins that was recently linked to Leber’s congenital amaurosis 3 (LCA). We report the first biochemical characterization of purified human RDH12 and analysis of its expression in human tissues. RDH12 exhibits ~2000-fold lower Km values for NADP+ and NADPH than for NAD+ and NADH and recognizes both retinoids and lipid peroxidation products (C9 aldehydes) as substrates. The kcat values of RDH12 for retinaldehydes and C9 aldehydes are similar, but the Km values are, in general, lower for retinoids. The enzyme exhibits the highest catalytic efficiency for all-trans-retinal (kcat/Km ~900 min−1 μM−1), followed by 11-cis-retinal (450 min−1 mM−1) and 9-cis-retinal (100 min−1 mM−1). Analysis of RDH12 activity toward retinoids in the presence of cellular retinol-binding protein (CRBP) type I or cellular retinaldehyde-binding protein (CRALBP) suggests that RDH12 utilizes the unbound forms of all-trans- and 11-cis-retinoids. As a result, the widely expressed CRBPI, which binds all-trans-retinol with much higher affinity than all-trans-retinaldehyde, restricts the oxidation of all-trans-retinol by RDH12, but has little effect on the reduction of all-trans-retinaldehyde, and CRALBP inhibits the reduction of 11-cis-retinal stronger than the oxidation of 11-cis-retinol, in accord with its higher affinity for 11-cis-retinal. Together, the tissue distribution of RDH12 and its catalytic properties suggest that, in most tissues, RDH12 primarily contributes to the reduction of all-trans-retinaldehyde; however, at saturating concentrations of peroxidic aldehydes in the cells undergoing oxidative stress, for example, photoreceptors, RDH12 might also play a role in detoxification of lipid peroxidation products. PMID:15865448

The effect of dietary trans alpha-linolenic acid on plasma lipids and platelet fatty acid composition: the TransLinE study.

PubMed

Sébédio, J L; Vermunt, S H; Chardigny, J M; Beaufrère, B; Mensink, R P; Armstrong, R A; Christie, W W; Niemelä, J; Hénon, G; Riemersma, R A

2000-02-01

To collect (i) baseline data and (ii) execute a large multicentre study examining the effect of trans alpha-linolenic acid on its incorporation into plasma lipids and on risk factors for coronary heart disease. Male volunteers were recruited and the habitual diet assessed by a 4-d weighed record. Fatty acid composition of plasma and platelet lipids were determined by gas chromatography at baseline. After a 6 week run-in period on a trans 'free' diet, male volunteers were randomised to consume 0.6 % of energy trans alpha-linolenic acid or to continue with a diet 'low' in trans alpha-linolenic acid for 6 weeks. Three European university research departments supported by the research and development departments of the food industry. Male volunteers (88) recruited by local advertisement. Replacement of 30 % of the fat of the habitual diet by margarine, oil and foods. Rapeseed oil was deodorised especially to produce the trans 'free' and 'high' trans foods for this study. The incorporation and conversion of trans alpha-linolenic acid into plasma lipids and platelets was assessed by gas chromatography and dietary compliance was verified by 4-d weighed record. Less trans alpha-linolenic acid isomers are incorporated into human plasma lipids in French volunteers than in Dutch or Scottish volunteers consuming their habitual diets. Trans 'free' alpha-linolenic acid-rich oil can be produced by careful deodorization during refining. The 'high' trans diet provided 1410+/-42 mg/d trans isomers of alpha-linolenic acid, whilst the 'low' trans group consumed 60+/-75 mg/d. The change in plasma lipid and platelet fatty acid composition documented that trans linolenic isomers are incorporated and converted to a trans isomer of eicosapentaenoic acid. Only the 15-trans alpha-linolenic acid is incorporated into plasma cholesteryl esters. The group consuming low trans diet had a slightly higher intake of fat, especially saturated and monounsaturated fat. Trans 'free' rapeseed oil, rich in

Low-Temperature Chemiluminescence From cis-1,4-Polybutadiene, 1,2-Polybutadiene, and trans-Polypentenamer at Temperatures Near Ambient

NASA Technical Reports Server (NTRS)

Nathan, Richard A.; Mendenhall, G. David; Birts, Michelle A.; Ogle, Craig A.; Golub, Morton A.

1978-01-01

The chemiluminescence emission at 25-60 C was measured from films of cis-1,4-polybutadiene, 1,2-polybutadiene, and trans-polypentenamer. The polymers were autoxidized previously in air 100 C, or allowed to react with singlet molecular oxygen in solution, and then cast into films. Values of beta(or k(sub d,((1)O2 yields (3)03)/k(sub r)((1)O2 + polymer yields products)) were determined in benzene for cis-1,4-polybutadiene and cis-1,4-polyisoprene, and for model compounds cis-3-hexene and cis-3-methyl-3-hexene by independent methods. The chemiluminescence emission from irradiated films of the polymers containing a dye sensitizer showed a complicated time dependence, and the results depended on the length of irradiation.

[Elimination of all trans fatty acids].

PubMed

Katan, M B

2008-02-09

At the start of the 20th century, the production of trans fatty acids was originally largely driven by the increasing demand for margarine. The two Dutch margarine firms Van den Bergh and Jurgens played an important role in this early development. In the early 1990s it was shown that trans fatty acids increase the risk of heart disease. Unilever, the successor to Van den Bergh and Jurgens, then took the lead in eliminating trans fatty acids from retail foods worldwide. As a result, intake in The Netherlands fell from 15 g per day in 1980 to 3 g per day in 2003. Dairy products and meat are now the major source of trans fatty acids. The effects on health of these ruminant trans fatty acids are unclear. There are three lessons to be learned from the rise and fall of trans fatty acids. First, a history of safe use does not guarantee safety of food components, because routine surveillance will fail to detect adverse effects on common illnesses with long incubation periods. Second, it shows that it is more effective and easier to change the composition of foods than to change consumer behaviour. And third, governments can have a major impact on consumers' health by mandating the use of healthier food ingredients.

Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients

USDA-ARS?s Scientific Manuscript database

Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy....

Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

NASA Astrophysics Data System (ADS)

Tomé, Maria; López, Concepción; González, Asensio; Ozay, Bahadir; Quirante, Josefina; Font-Bardía, Mercè; Calvet, Teresa; Calvis, Carme; Messeguer, Ramon; Baldomá, Laura; Badía, Josefa

2013-09-01

The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c·CH2Cl2 and 5c confirm: (a) the existence of a Pt-Nindole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4‧R1)-3NOMe-5R2 [with R1 = R2 = H (3a); R1 = Cl, R2 = H (3b) and R1 = H, R2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-I have been performed, in order to get further insights into their mechanism of action.

Trans -cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis –induced inflammation and virulence

PubMed Central

Rao, Vivek; Gao, Feng; Chen, Bing; Jacobs, William R.; Glickman, Michael S.

2006-01-01

Recent studies have shown that fine structural modifications of Mycobacterium tuberculosis cell envelope lipids mediate host cell immune activation during infection. One such alteration in lipid structure is cis-cyclopropane modification of the mycolic acids on trehalose dimycolate (TDM) mediated by proximal cyclopropane synthase of α mycolates (pcaA), a proinflammatory lipid modification during early infection. Here we examine the pathogenetic role and immunomodulatory function of mycolic acid cyclopropane stereochemistry by characterizing an M. tuberculosis cyclopropane–mycolic acid synthase 2 (cmaA2) null mutant (ΔcmaA2) that lacks trans-cyclopropanation of mycolic acids. Although titers of WT and ΔcmaA2 organisms were identical during mouse infection, ΔcmaA2 bacteria were hypervirulent while inducing larger granulomas than WT M. tuberculosis. The hypervirulence of the ΔcmaA2 strain depended on host TNF-α and IFN-γ. Loss of trans-cyclopropanation enhanced M. tuberculosis–induced macrophage inflammatory responses, a phenotype that was transferable with petroleum ether extractable lipids. Finally, purified TDM lacking trans-cyclopropane rings was 5-fold more potent in stimulating macrophages. These results establish cmaA2-dependent trans-cyclopropanation of TDM as a suppressor of M. tuberculosis–induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation. PMID:16741578

Trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) treatment and caloric restriction differentially affect adipocyte cell turnover in obese and lean mice.

PubMed

Yeganeh, Azadeh; Zahradka, Peter; Taylor, Carla G

2017-11-01

Caloric restriction (CR) is one of the most promising strategies for weight loss but is associated with loss of lean mass, whereas compounds such as trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) have been promoted as antiobesity agents. To compare the mechanisms of weight reduction by CR and t10-c12 CLA, body composition, glucose control, and characteristics of adipose tissue with respect to cell turnover (stem cells and preadipocytes, apoptosis and autophagy) and Tbx-1 localization were examined in obese db/db mice and lean C57BL/6J mice undergoing CR or fed CLA isomers (0.4% w/w c9-t11 or t10-c12) for 4 weeks. Our findings show that the t10-c12 CLA reduced whole-body fat mass by decreasing all fat depots (visceral, inguinal, brown/interscapular), while CR lowered both whole-body fat and lean mass in obese mice. t10-c12 CLA elevated blood glucose in both obese and lean mice, while glycemia was not altered by CR. The adipocyte stem cell population remained unchanged; however, t10-c12 CLA reduced and CR elevated the proportion of immature adipocytes in obese mice, suggesting differential effects on adipocyte maturation. t10-c12 CLA reduced apoptosis (activated caspase-3) in both obese and lean mice but did not alter autophagy (LC3II/LC3I). Nuclear Tbx-1, a marker of metabolically active beige adipocytes, was greater in the adipose of t10-c12 CLA-fed animals. Thus, weight loss achieved via t10-c12 CLA primarily involves fat loss and more cells with Tbx-1 localized to the nucleus, while CR operates through a mechanism that reduces both lean and fat mass and blocks adipocyte differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

NMR analysis of cleaved Escherichia coli thioredoxin (1-73/74-108) and its P76A variant: cis/trans peptide isomerization.

PubMed Central

Yu, W. F.; Tung, C. S.; Wang, H.; Tasayco, M. L.

2000-01-01

Inspection of high resolution three-dimensional (3D) structures from the protein database reveals an increasing number of cis-Xaa-Pro and cis-Xaa-Yaa peptide bonds. However, we are still far from being able to predict whether these bonds will remain cis upon single-site substitution of Pro or Yaa and/or cleavage of a peptide bond close to it in the sequence. We have chosen oxidized Escherichia coli thioredoxin (Trx), a member of the Trx superfamily with a single alpha/beta domain and cis P76 to determine the effect of single-site substitution and/or cleavage on this isomer. Standard two-dimensional (2D) NMR analysis were performed on cleaved Trx (1-73/74-108) and its P76A variant. Analysis of the NOE connectivities indicates remarkable similarity between the secondary and supersecondary structure of the noncovalent complexes and Trx. Analysis of the 2D version of the HCCH-TOCSY and HMQC-NOESY-HMQC and 13C-filtered HMQC-NOESY spectra of cleaved Trx with uniformly 13C-labeled 175 and P76 shows surprising conservation of both cis P76 and packing of 175 against W31. A similar NMR analysis of its P76A variant provides no evidence for cis A76 and shows only subtle local changes in both the packing of 175 and the interstrand connectivities between its most protected hydrophobic strands (beta2 and beta4). Indeed, a molecular simulation model for the trans P76A variant of Trx shows only subtle local changes around the substitution site. In conclusion, cleavage of R73 is insufficient to provoke cis/trans isomerization of P76, but cleavage and single-site substitution (P76A) favors the trans isomer. PMID:10739243

trans-10,cis-12 conjugated linoleic acid alters lipid metabolism of goat mammary epithelial cells by regulation of de novo synthesis and the AMPK signaling pathway.

PubMed

Zhang, T Y; Huang, J T; Tian, H B; Ma, Y; Chen, Z; Wang, J J; Shi, H P; Luo, J

2018-06-01

The trans-10,cis-12 isomer of conjugated linoleic acid (t10c12-CLA) is a biohydrogenation intermediate in the rumen and has been shown to cause milk fat depression in dairy goats. However, few studies have focused on the in vitro molecular mechanisms involved in the response of the goat mammary gland to t10c12-CLA. In the present study, RNA sequencing technology was used to investigate the effects of t10c12-CLA on goat mammary epithelial cells. From the data, 25,153 annotated transcripts were obtained, and differentially expressed genes were selected based on a false discovery rate <0.05. Candidate genes and potent cellular signaling pathways were identified through Gene Ontology (GO) and pathway analysis. Next, real-time quantitative PCR and Western blot analyses were used to verify the results of the RNA sequencing data. The results indicated that t10c12-CLA inhibits fatty acid synthesis through downregulation of genes involved in de novo fatty acid synthesis, and this process is likely correlated with the activation of the AMP-activated protein kinase signaling pathways. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Anion-assisted trans-cis isomerization of palladium(II) phosphine complexes containing acetanilide functionalities through hydrogen bonding interactions.

PubMed

Lu, Xiao-Xia; Tang, Hau-San; Ko, Chi-Chiu; Wong, Jenny Ka-Yan; Zhu, Nianyong; Yam, Vivian Wing-Wah

2005-03-28

The anion-assisted shift of trans-cis isomerization equilibrium of a palladium(II) complex containing acetanilide functionalities brought about by allosteric hydrogen bonding interactions has been established by UV/Vis, 1H NMR, 31P NMR and ESI-MS studies.

Herpesvirus papio contains a plasmid origin of replication that acts in cis interspecies with an Epstein-Barr virus trans-acting function.

PubMed Central

Pesano, R L; Pagano, J S

1986-01-01

Herpesvirus papio (HVP) and Epstein-Barr virus (EBV) are closely related biologically and biochemically; lymphoblastoid cells infected with either virus contain episomal viral DNA. The putative origin of replication for EBV plasmids (oriP) has been assigned to a 1,790-base-pair fragment (cis) in the short unique region of the genome which requires a viral function supplied in trans from elsewhere in the genome (J. Yates, N. Warren, D. Reisman, and B. Sugden, Proc. Natl. Acad. Sci. USA 81:3806-3810, 1984). We report here the identification of the putative origin of replication (cis) in HVP; we assigned it to the HVP EcoRI K fragment. The results indicate that the HVP replication process requires both a cis and a trans-acting function, analogous to that found in EBV. Images PMID:3023667

A human induced pluripotent stem cell-based in vitro assay predicts developmental toxicity through a retinoic acid receptor-mediated pathway for a series of related retinoid analogues.

PubMed

Palmer, Jessica A; Smith, Alan M; Egnash, Laura A; Colwell, Michael R; Donley, Elizabeth L R; Kirchner, Fred R; Burrier, Robert E

2017-10-01

The relative developmental toxicity potency of a series of retinoid analogues was evaluated using a human induced pluripotent stem (iPS) cell assay that measures changes in the biomarkers ornithine and cystine. Analogue potency was predicted, based on the assay endpoint of the ornithine/cystine (o/c) ratio, to be all-trans-retinoic acid>TTNPB>13-cis-retinoic acid≈9-cis-retinoic acid>acitretin>etretinate>retinol. These rankings correlate with in vivo data and demonstrate successful application of the assay to rank a series of related toxic and non-toxic compounds. The retinoic acid receptor α (RARα)-selective antagonist Ro 41-5253 inhibited the cystine perturbation caused by all-trans-retinoic acid, TTNPB, 13-cis-retinoic acid, 9-cis-retinoic acid, and acitretin. Ornithine was altered independent of RARα in all retinoids except acitretin. These results suggest a role for an RARα-mediated mechanism in retinoid-induced developmental toxicity through altered cystine metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of UDP-glucuronosyltransferase isoforms in 13-cis retinoic acid metabolism in humans.

PubMed

Rowbotham, Sophie E; Illingworth, Nicola A; Daly, Ann K; Veal, Gareth J; Boddy, Alan V

2010-07-01

13-cis Retinoic acid (13cisRA, isotretinoin) is an important drug in both dermatology, and the treatment of high-risk neuroblastoma. 13cisRA is known to undergo cytochrome P450-mediated oxidation, mainly by CYP2C8, but phase II metabolic pathways have not been characterized. In the present study, the glucuronidation activities of human liver (HLM) and intestinal microsomes (HIM), as well as a panel of human UDP-glucuronosyltransferases (UGTs) toward both 13cisRA and the 4-oxo metabolite, 4-oxo 13cisRA, were compared using high-performance liquid chromatography. Both HLM and, to a greater extent, HIM catalyzed the glucuronidation of 13cisRA and 4-oxo 13cisRA. Based on the structures of 13cisRA and 4-oxo 13cisRA, the glucuronides formed are conjugated at the terminal carboxylic acid. Further analysis revealed that UGT1A1, UGT1A3, UGT1A7, UGT1A8, and UGT1A9 were the major isoforms responsible for the glucuronidation of both substrates. For 13cisRA, a pronounced substrate inhibition was observed with individual UGTs and with HIM. UGT1A3 exhibited the highest rate of activity toward both substrates, and a high rate of activity toward 13cisRA glucuronidation was also observed with UGT1A7. However, for both substrates, K(m) values were above concentrations reported in clinical studies. Therefore, UGT1A9 is likely to be the most important enzyme in the glucuronidation of both substrates as this enzyme had the lowest K(m) and is expressed in both the intestine and at high levels in the liver.

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo-Fatty Acids Produced by Gut Bacteria are Responsible for CCK Secretion in STC-1 Cells via GPR40.

PubMed

Hira, Tohru; Ogasawara, Shono; Yahagi, Asuka; Kamachi, Minami; Li, Jiaxin; Nishimura, Saki; Sakaino, Masayoshi; Yamashita, Takatoshi; Kishino, Shigenobu; Ogawa, Jun; Hara, Hiroshi

2018-06-25

The secretion of gut hormones, such as cholecystokinin (CCK) is stimulated by fatty acids. Although a chain length-dependent mechanism has been proposed, other structural relationships to releasing activity remain unclear. We aimed to elucidate specific structures in fatty acids that are responsible for their CCK-releasing activity, and related sensing mechanisms in enteroendocrine cells. We examined CCK secretory activities in a murine CCK-producing cell line STC-1 by exposing the cells to various modified fatty acids produced by gut lactic acid bacteria. The effects of fatty acids on gastric emptying rate as a CCK-mediated function were examined using acetaminophen- and phenol red-methods in rats. Out of more than thirty octadecanoic (C18)-derived fatty acids tested, five oxo-fatty acids potently stimulated CCK secretion without cytotoxic effects in STC-1 cells. Three fatty acids had a distinct specific structure containing one double-bond, whereas the other two had two double-bonds, nearby an oxo residue. CCK secretion induced by representative fatty acids (10-oxo-trans-11-18:1 and 13-oxo-cis-9,cis-15-18:2) was attenuated by a fatty acid-receptor GPR40 antagonist. Oral administration of 13-oxo-cis-9,cis-15-18:2 lowered the gastric emptying rate in rats in a dose- and structure-dependent manner. These results revealed a novel fatty acid-sensing mechanism in enteroendocrine cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey following a nonteratogenic dosing regimen with all-trans-retinoic acid.

PubMed

Tzimas, G; Nau, H; Hendrickx, A G; Peterson, P E; Hummler, H

1996-11-01

Retinoids often exhibit a complex metabolic pattern and differential transplacental kinetics, which make it difficult to pinpoint the proximate compound responsible for the observed teratogenic effect. We have therefore studied the pharmacokinetics and metabolism of all-trans-retinoic acid (all-trans-RA) in cynomolgus monkeys following application of a nonteratogenic dosing regimen and compared the results with corresponding data from a previous study with a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]. All-trans-RA was administered to pregnant cynomolgus monkeys (Macaca fascicularis) by nasogastric intubation at a dose of 5 mg/kg body wt once daily from gestational day (GD) 16 to 26 and twice daily at 8-h intervals from GD 27 to 31. Examination of the fetuses of four dams on GD 100 +/- 2 showed no embryotoxic or teratogenic effects of the applied dosing regimen (Experiment 1). Maternal plasma retinoid pharmacokinetics on GD 16, 26, and 31 as well as embryonic retinoid profiles after the last drug administration on GD 31 were determined in thirteen further dams (Experiment 2). All-trans-RA reached much lower plasma concentrations after the last two treatments on GD 31 than after the first one on GD 16 and the eleventh one on GD 26 (0-24-h area-under-the-concentration-time-curve (AUC) values: 104 +/- 59 ng x h/ml (after the last treatment on GD 31), 189 +/- 110 (GD 16) and 393 +/- 305 ng x h/ml (GD 26). The predominant plasma metabolites of all-trans-RA were its beta-glucuronide and the beta-glucuronide of all-trans-4-oxo-RA. Both of these retinoids accumulated in the plasma during the period of treatment and displayed AUC values 5- to 30-fold higher than those of all-trans-RA. Embryonic concentrations of all-trans-RA were not increased over endogenous levels after the last administration on GD 31 when plasma concentrations were low. To evaluate the placental transport of all-trans-RA in the presence of high plasma

Theoretical prediction of nuclear magnetic shieldings and indirect spin-spin coupling constants in 1,1-, cis-, and trans-1,2-difluoroethylenes

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

Nozirov, Farhod, E-mail: teobaldk@gmail.com, E-mail: farhod.nozirov@gmail.com; Stachów, Michał, E-mail: michal.stachow@gmail.com; Kupka, Teobald, E-mail: teobaldk@gmail.com, E-mail: farhod.nozirov@gmail.com

2014-04-14

A theoretical prediction of nuclear magnetic shieldings and indirect spin-spin coupling constants in 1,1-, cis- and trans-1,2-difluoroethylenes is reported. The results obtained using density functional theory (DFT) combined with large basis sets and gauge-independent atomic orbital calculations were critically compared with experiment and conventional, higher level correlated electronic structure methods. Accurate structural, vibrational, and NMR parameters of difluoroethylenes were obtained using several density functionals combined with dedicated basis sets. B3LYP/6-311++G(3df,2pd) optimized structures of difluoroethylenes closely reproduced experimental geometries and earlier reported benchmark coupled cluster results, while BLYP/6-311++G(3df,2pd) produced accurate harmonic vibrational frequencies. The most accurate vibrations were obtained using B3LYP/6-311++G(3df,2pd)more » with correction for anharmonicity. Becke half and half (BHandH) density functional predicted more accurate {sup 19}F isotropic shieldings and van Voorhis and Scuseria's τ-dependent gradient-corrected correlation functional yielded better carbon shieldings than B3LYP. A surprisingly good performance of Hartree-Fock (HF) method in predicting nuclear shieldings in these molecules was observed. Inclusion of zero-point vibrational correction markedly improved agreement with experiment for nuclear shieldings calculated by HF, MP2, CCSD, and CCSD(T) methods but worsened the DFT results. The threefold improvement in accuracy when predicting {sup 2}J(FF) in 1,1-difluoroethylene for BHandH density functional compared to B3LYP was observed (the deviations from experiment were −46 vs. −115 Hz)« less

8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation

PubMed Central

Jiao, Bo; Ren, Zhi-Hong; Liu, Ping; Chen, Li-Juan; Shi, Jing-Yi; Dong, Ying; Ablain, Julien; Shi, Lin; Gao, Li; Hu, Jun-Pei; Ren, Rui-Bao; de Thé, Hugues; Chen, Zhu; Chen, Sai-Juan

2013-01-01

The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3′, 5′-cyclic monophosphate (8-CPT-cAMP) enhances cellular differentiation and improves gene trans-activation by ATRA in leukemic blasts. Mechanistically, in combination with ATRA, 8-CPT-cAMP activates PKA, causing phosphorylation of PLZF/RARα at Ser765 and resulting in increased dissociation of the silencing mediator for retinoic acid and thyroid hormone receptors/nuclear receptor corepressor from PLZF/RARα. This process results in changes of local chromatin and transcriptional reactivation of the retinoic acid pathway in leukemic cells. Meanwhile, 8-CPT-cAMP also potentiated ATRA-induced degradation of PLZF/RARα through its Ser765 phosphorylation. In vivo treatment of the t(11;17) APL mouse model demonstrated that 8-CPT-cAMP could significantly improve the therapeutic effect of ATRA by targeting a leukemia-initiating cell activity. This combined therapy, which induces enhanced differentiation and oncoprotein degradation, may benefit t(11;17) APL patients. PMID:23382200

Photocatalytic production and processing of conjugated linoleic acid-rich soy oil.

PubMed

Jain, Vishal P; Proctor, Andrew

2006-07-26

Daily intake of conjugated linoleic acid (CLA), an anticarcinogenic, antiatherosclerotic, antimutagenic agent, and antioxidant, from dairy and meat products is substantially less than estimated required values. The objective of this study was to obtain CLA-rich soybean oil by a customized photochemical reaction system with an iodine catalyst and evaluate the effect of processing on iodine and iodo compounds after adsorption. After 144 h of irradiation, a total CLA yield of 24% (w/w) total oil was obtained with 0.15% (w/w) iodine. Trans,trans isomers (17.5%) formed the majority of the total yield and are also associated with health benefits. The isomers cis-9,trans-11 and trans-10,cis-12 CLA, associated with maximum health benefits, formed approximately 3.5% of the total oil. This amount is quite significant considering that total CLA obtained from dairy sources is only 0.6%. ATR-FTIR, 1H NMR, and GC-MS analyses indicated the absence of peroxide and aldehyde protons, providing evidence that secondary lipid oxidation products were not formed during the photochemical reaction. Adsorption processing vastly reduced the iodine and iodocompounds without CLA loss. Photocatalysis significantly increased the levels of CLA in soybean oil.

Formation and evolution of monoepoxy fatty acids in thermoxidized olive and sunflower oils and quantitation in used frying oils from restaurants and fried-food outlets.

PubMed

Velasco, Joaquín; Marmesat, Susana; Bordeaux, Olivier; Márquez-Ruiz, Gloria; Dobarganes, Carmen

2004-07-14

The formation and evolution of monoepoxy fatty acids, arising from oleic and linoleic acids, were investigated in olive oil and conventional sunflower oil, representatives of monounsaturated and polyunsaturated oils, respectively, during thermoxidation at 180 degrees C for 5, 10, and 15 h. Six monoepoxy fatty acids, cis-9,10- and trans-9,10-epoxystearate, arising from oleic acid, and cis-9,10-, trans-9,10-, cis-12,13-, and trans-12,13-epoxyoleate, arising from linoleic acid, were analyzed by gas chromatography after oil derivatization to fatty acid methyl esters. Considerable amounts, ranging from 4.29 to 14.24 mg/g of oil in olive oil and from 5.10 to 9.44 mg/g of oil in sunflower oil, were found after the heating periods assayed. Results showed that the monoepoxides quantitated constituted a major group among the oxidized fatty acid monomers formed at high temperature. For similar levels of degradation, higher contents of the monoepoxides were found in olive oil than in sunflower oil. Ten used frying oils from restaurants and fried-food outlets in Spain were analyzed to determine the contents of the monoepoxides in real frying oil samples. Levels ranged from 3.37 to 14.42 mg/g of oil. Results show that, for similar degradation levels, the monoepoxides were more abundant in the monounsaturated oils than in the polyunsaturated oils.

Distortions induced in double-stranded oligonucleotides by the binding of cis- or trans-diammine-dichloroplatinum(II) to the d(GTG) sequence.

PubMed Central

Anin, M F; Leng, M

1990-01-01

Conformational changes induced in double-stranded oligonucleotides by the binding of trans- or cis-diamminedichloro platinum(II) to the d(GTG) sequence have been characterized by means of melting temperatures, electrophoretic migrations in non-denaturing polyacrylamide gels, reactivities with the artificial nuclease Phenanthroline-copper and with chemical probes. The cis-platinum adduct behaves more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 25-30 degrees. The double helix is locally denatured over 2 base pairs (corresponding to the platinated 5'G residue and the central T residue) and is distorted over 4-5 base pairs. The trans-platinum adduct behaves also more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 60 degrees. The double helix is locally denatured over 4 base pairs (corresponding to the immediately 5'T residue adjacent to the adduct and to the three base residues of the adduct). Both the cis- and trans-platinum adducts decrease the thermal stability of the double helix. Images PMID:2388824

A new approach to highly sensitive determination of retinoic acid isomers by preconcentration with CdSe quantum dots.

PubMed

Torabi, Behzad; Shemirani, Farzaneh

2014-03-01

Unusual amounts of retinoic acid (RA) isomers play an important role in abnormal morphological development of mammals; such as rat embryos. Each isomer of RA has a unique function in first steps of embryonic life. In the current study, a new method for preconcentration and simultaneous determination of all-trans retinoic acid, 13-cis retinoic acid, 9-cis retinoic acid and 9,13-di-cis retinoic acid in rat whole rudimentary embryo culture (RWEC) has been developed. RA isomers were extracted from samples by conjugation to appropriate amount of surface modified CdSe quantum dots (QDs) prior to HPLC/UV determination. In order to quickly release of the analytes with unchanged form, separated RA-QD conjugation were irradiated by intensive near infrared wavelength (NIR). Low energy NIR irradiation results in maintaining the primary forms of RA isomers during the release. The conjugation and release mechanisms were described and experimental parameters were investigated in detail. Under optimized conditions, the method was linear in the range of 0.040-34.600 pmol g(-1) for all-trans RA (R(2)=0.9996), 0.070-34.200 pmol g(-1) for 13-cis RA (R(2)=0.9992), 0.050-35.300 pmol g(-1) for 9,13-di-cis RA (R(2)=0.9998) and 0.050-32.900 pmol g(-1) for 9-cis RA (R(2)=0.9990). The present method can be useful for retinoic acid monitoring in clinical studies. © 2013 Published by Elsevier B.V.

Anti-inflammatory effects of conjugated linoleic acid isomers and essential fatty acids in bovine mammary epithelial cells.

PubMed

Dipasquale, D; Basiricò, L; Morera, P; Primi, R; Tröscher, A; Bernabucci, U

2018-01-09

Fatty acids are important modulators of inflammatory responses, in particular, n-3 and n-6 essential fatty acids and CLA have received particular attention for their ability to modulate inflammation. The objectives of this study were to compare the effects of CLA and essential fatty acids on the expression of pro and anti- inflammatory cytokines and their protective efficacy against inflammatory status in mammary gland by an in vitro model based on bovine mammary epithelial cells (BME-UV1). Bovine mammary epithelial cells were treated with complete medium containing either 50 µM of cis-9, trans-11 CLA (c9,t11 CLA) or trans-10, cis-12 CLA (t10,c12 CLA) or (α)-linolenic acid (aLnA) or (γ)-linolenic acid (gLnA) or linoleic acid (LA). After 48 h by fatty acids administration the cells were treated for 3 h with 20 µM of lipopolysaccharide (LPS) to induce inflammatory stimulus. Reactive oxygen species (ROS) production after treatments was assessed to verify and to compare the potential protection of different fatty acids against LPS-induced oxidative stress. The messenger RNA abundance of bovine pro and anti-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukine-10 (IL-10)) and peroxisome proliferator receptor-α/γ (PPARγ/α) were determined in BME-UV1 by real-time PCR. The results showed that cells treated with fatty acids and LPS increased ROS production compared with control cells. Among treatments, cells treated with c9,t11 CLA and t10,c12 CLA isomers revealed significant lower levels of ROS production compared with other fatty acids. All fatty acids reduced the gene expression of pro- and anti-inflammatory cytokines. Among fatty acids, t10,c12 CLA, LA and gLnA showed an homogeneous reduction of the three pro-inflammatory cytokines and this may correspond to more balanced and efficient physiological activity and may trigger a better protective effect. The PPARγ gene expression was

One-pot conjugated linoleic acid production from castor oil by Rhizopus oryzae lipase and resting cells of Lactobacillus plantarum.

PubMed

Khaskheli, Abid Ali; Talpur, Farah Naz; Cebeci Aydin, Aysun; Jawaid, Sana; Surhio, Muhammad Ali; Afridi, Hassan Imran

2017-10-01

Conjugated linoleic acid (CLA) has attracted as novel type of fatty acids having unusual health-promoting properties such as anticarcinogenic and antiobesitic effects. The present work employed castor oil as substrate for one-pot production of CLA using washed cells of Lactobacillus plantarum (L. plantarum) and lipases as catalysts. Among the screened lipases, the lipase Rhizopus oryzae (ROL) greatly assisted resting cells to produce CLA. Mass spectral analysis of the product showed that two major isomers of CLA were produced in the reaction mixture i.e. cis-9, trans-11 56.55% and trans-10, cis-12 43.45%. Optimum factors for CLA synthesis were found as substrate concentration (8 mg/mL), pH (6.5), washed cell concentration (12% w/v), and incubation time of 20 h. Hence, the combination of ROL with L. plantarum offers one pot production of CLA selectively using castor oil as a cost-effective substrate.

9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons.

PubMed

Reiner, David J; Yu, Seong-Jin; Shen, Hui; He, Yi; Bae, Eunkyung; Wang, Yun

2014-04-01

Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-Cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H(2)O(2) and oxygen-glucose deprivation in vitro as well as infarction and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling (TUNEL) labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4×) one day later. Locomotor behavior was measured 2 days after surgery for a period of 48 h. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA-mediated neurodegeneration in dopaminergic neurons via upregulation of BMP.

9-cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons

PubMed Central

Reiner, David J; Yu, Seong-Jin; Shen, Hui; He, Yi; Bae, Eunkyung; Wang, Yun

2013-01-01

Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 and oxygen-glucose deprivation in vitro as well as infarction and TUNEL labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4x) one day later. Locomotor behavior was measured two days after surgery for a period of 48 hours. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA -mediated neurodegeneration in dopaminergic neurons via upregulation of BMP. PMID:23884514

Selected cis- and trans-3-fluorostyrene rotamers studied by two-color resonant two-photon mass-analyzed threshold ionization spectroscopy

NASA Astrophysics Data System (ADS)

Wu, Pei Ying; Tzeng, Wen Bih

2015-10-01

We applied two-color resonant two-photon ionization and mass-analyzed threshold ionization techniques to record the vibronic, photoionization efficiency, and cation spectra of the selected rotamers of 3-fluorostyrene. The adiabatic ionization energies of cis- and trans-3-fluorostyrene were determined to be 69 960 ± 5 and 69 856 ± 5 cm-1, respectively. Cation vibrations 10a, 15, 6b, and 12 of both rotamers have been found to have frequencies of 218, 404, 452, and 971 cm-1, respectively. This finding shows that the relative orientation of the vinyl group with respect to the F atom does not affect these vibrations of the 3-fluorostyrene cation. Our one-dimensional potential energy surface calculations support that the cis-trans isomerization of 3-fluorostyrene does not occur under the present experimental conditions.

Plasmodium falciparum: differing effects of non-esterified fatty acids and phospholipids on intraerythrocytic growth in serum-free medium.

PubMed

Asahi, Hiroko; Izumiyama, Shinji; Tolba, Mohammed Essa Marghany; Kwansa-Bentum, Bethel

2011-03-01

Different combinations of non-esterified fatty acids (NEFA) had variable effects on intraerythrocytic growth of Plasmodium falciparum. All stages of the parasite cultured in medium supplemented with cis-9-octadecenoic acid (C18:1-cis-9), hexadecanoic acid (C16:0), phospholipids (Pld) and bovine albumin free of NEFA were similar to those grown in complete growth medium. Three typical growth patterns indicating suppressed schizogony (SS), suppressed formation of merozoites (SMF), and inhibited invasion of merozoites (IMI) resulted from culture in other combinations of lipids. Unsaturated or saturated NEFA with longer or shorter carbon chains than C18:1-cis-9 or C16:0, higher degree of unsaturation, and trans-forms mainly resulted in SS and SMF effects. However, IMI or partial IMI was observed with tetradecanoic acid or octadecanoic acid enriched with C18:1-cis-9, and cis-9-hexadecenoic acid plus C16:0. Isoforms of C18:1-cis-9 also mainly resulted in partial IMI. SMF also occurred with C18:1-cis-9 plus C16:0 in the absence of Pld. Thus different NEFA exerted distinct roles in erythrocytic growth of the parasite by sustaining development at different stages. Copyright © 2010 Elsevier Inc. All rights reserved.

Comprehensive analysis of mycolic acid subclass and molecular species composition of Mycobacterium bovis BCG Tokyo 172 cell wall skeleton (SMP-105).

PubMed

Uenishi, Yuko; Fujita, Yukiko; Kusunose, Naoto; Yano, Ikuya; Sunagawa, Makoto

2008-02-01

The mycobacterial cell envelope consists of a characteristic cell wall skeleton (CWS), a mycoloyl arabinogalactan peptidoglycan complex, and related hydrophobic components that contribute to the cell surface properties. Since mycolic acids have recently been reported to play crucial roles in host immune response, detailed molecular characterization of mycolic acid subclasses and sub-subclasses of CWS from Mycobacterium bovis BCG Tokyo 172 (SMP-105) was performed. Mycolic acids were liberated by alkali hydrolysis from SMP-105, and their methyl esters were separated by silica gel TLC into three subclasses: alpha-, methoxy-, and keto-mycolates. Each mycolate subclass was further separated by silver nitrate (AgNO(3))-coated silica gel TLC into sub-subclasses. Molecular weights of individual mycolic acid were determined by MALDI-TOF mass spectrometry. alpha-Mycolates were sub-grouped into cis, cis-dicyclopropanoic (alpha1), and cis-monocyclopropanoic-cis-monoenoic (alpha2) series; methoxy-mycolates were sub-grouped into cis-monocyclopropanoic (m1), trans-monocyclopropanoic (m2), trans-monoenoic (m3), cis-monocyclopropanoic-trans-monoenoic (m4), cis-monoenoic (m5), and cis-monocyclopropanoic-cis-monoenoic (m6) series; and keto-mycolates were sub-grouped into cis-monocyclopropanoic (k1), trans-monocyclopropanoic (k2), trans-monoenoic (k3), cis-monoenoic (k4), and cis-monocyclopropanoic-cis-monoenoic (k5) series. The position of each functional group, including cyclopropane rings and methoxy and keto groups, was determined by analysis of the meromycolates with fast atom bombardment (FAB) mass spectrometry and FAB mass-mass spectrometry, and the cis/trans ratio of cyclopropane rings and double bonds were determined by NMR analysis of methyl mycolates. Mycolic acid subclass and molecular species composition of SMP-105 showed characteristic features including newly-identified cis-monocyclopropanoic-trans-monoenoic mycolic acid (m4).