High-resolution structures of Lactobacillus salivarius transketolase in the presence and absence of thiamine pyrophosphate.

PubMed

Lukacik, Petra; Lobley, Carina M C; Bumann, Mario; Arena de Souza, Victoria; Owens, Raymond J; O'Toole, Paul W; Walsh, Martin A

2015-10-01

Probiotic bacterial strains have been shown to enhance the health of the host through a range of mechanisms including colonization, resistance against pathogens, secretion of antimicrobial compounds and modulation of the activity of the innate immune system. Lactobacillus salivarius UCC118 is a well characterized probiotic strain which survives intestinal transit and has many desirable host-interaction properties. Probiotic bacteria display a wide range of catabolic activities, which determine their competitiveness in vivo. Some lactobacilli are heterofermentative and can metabolize pentoses, using a pathway in which transketolase and transaldolase are key enzymes. L. salivarius UCC118 is capable of pentose utilization because it encodes the key enzymes on a megaplasmid. The crystal structures of the megaplasmid-encoded transketolase with and without the enzyme cofactor thiamine pyrophosphate have been determined. Comparisons with other known transketolase structures reveal a high degree of structural conservation in both the catalytic site and the overall conformation. This work extends structural knowledge of the transketolases to the industrially and commercially important Lactobacillus genus.

Thiamine supplementation facilitates thiamine transporter expression in the rumen epithelium and attenuates high-grain-induced inflammation in low-yielding dairy cows.

PubMed

Pan, X H; Yang, L; Beckers, Y; Xue, F G; Tang, Z W; Jiang, L S; Xiong, B H

2017-07-01

An experiment was conducted to uncover the effects of increasing dietary grain levels on expression of thiamine transporters in ruminal epithelium, and to assess the protective effects of thiamine against high-grain-induced inflammation in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 ± 16.9 kg of body weight, 180 ± 6 d in milk; mean ± standard deviation) were randomly assigned to a replicated 3 × 3 Latin square design trial. Three treatments were control (20% dietary starch, dry matter basis), high-grain diet (HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and thiamine contents in rumen and blood, and plasma inflammatory cytokines were detected; a rumen papillae biopsy was taken on d 21 to determine the gene and protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2 kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to 3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs. 8.97 μg/L) and blood (11.66 vs. 17.63 μg/L), and the relative expression value of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin units/mL), and higher plasma concentrations of lipopolysaccharide binding protein and pro-inflammatory cytokines when compared with the control group. The gene and protein expression of tumor necrosis factor α (TNFα), IL1B, and IL6 in rumen epithelium increased when cows were fed the HG diet, indicating that local inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG-fed cows were reversed by thiamine

Thiamine and fatty acid content of walleye tissue from three southern U.S. reservoirs

USGS Publications Warehouse

Honeyfield, D.C.; Vandergoot, C.S.; Bettoli, P.W.; Hinterkopf, J.P.; Zajicek, J.L.

2007-01-01

We determined the thiamine concentration in egg, muscle, and liver tissues of walleyes Sander vitreus and the fatty acid content of walleye eggs from three southern U.S. reservoirs. In two Tennessee reservoirs (Dale Hollow and Center Hill), in which there were alewives Alosa pseudoharengus in the forage base, natural recruitment of walleyes was not occurring; by contrast in Lake James Reservoir, North Carolina, where there were no alewives, the walleye population was sustained via natural recruitment. Female walleye tissues were collected and assayed for thiamine (vitamin B1) and fatty acid content. Thiamine pyrophosphate was found to be the predominant form of thiamine in walleye eggs. In 2000, mean total egg thiamine concentrations were similar among Center Hill, Dale Hollow, and Lake James reservoirs (2.13, 3.14, and 2.77 nmol thiamine/g, respectively). Egg thiamine concentration increased as maternal muscle (r 2 = 0.73) and liver (r2 = 0.68) thiamine concentration increased. Walleye egg thiamine does not appear to be connected to poor natural reproduction in Tennessee walleyes. Threadfin shad Dorosoma petenense, which are found in all three reservoirs, had higher thiaminase activity than alewives. Six fatty acids differed among the walleye eggs for the three reservoirs. Two were physiologically important fatty acids, arachidonic acid (20:4[n-6]) and docosahexaenoic acid (22:6[n-3]), which are important eicosanoid precursors involved in the regulation of biological functions, such as immune response and reproduction. ?? Copyright by the American Fisheries Society 2007.

The Thiamine Biosynthesis Gene THI1 Promotes Nodule Growth and Seed Maturation1

PubMed Central

Nagae, Miwa; Kawaguchi, Masayoshi; Takeda, Naoya

2016-01-01

Thiamine (vitamin B1) is essential for living organisms. Unlike animals, plants can synthesize thiamine. In Lotus japonicus, the expression of two thiamine biosynthesis genes, THI1 and THIC, was enhanced by inoculation with rhizobia but not by inoculation with arbuscular mycorrhizal fungi. THIC and THI2 (a THI1 paralog) were expressed in uninoculated leaves. THI2-knockdown plants and the transposon insertion mutant thiC had chlorotic leaves. This typical phenotype of thiamine deficiency was rescued by an exogenous supply of thiamine. In wild-type plants, THI1 was expressed mainly in roots and nodules, and the thi1 mutant had green leaves even in the absence of exogenous thiamine. THI1 was highly expressed in actively dividing cells of nodule primordia. The thi1 mutant had small nodules, and this phenotype was rescued by exogenous thiamine and by THI1 complementation. Exogenous thiamine increased nodule diameter, but the level of arbuscular mycorrhizal colonization was unaffected in the thi1 mutant or by exogenous thiamine. Expression of symbiotic marker genes was induced normally, implying that mainly nodule growth was delayed in the thi1 mutant. Furthermore, this mutant formed many immature seeds with reduced seed weight. These results indicate that thiamine biosynthesis mediated by THI1 enhances nodule enlargement and is required for seed development in L. japonicus. PMID:27702844

Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1

PubMed Central

Rao, Feng; Xu, Jing; Fu, Chenglai; Cha, Jiyoung Y.; Gadalla, Moataz M.; Xu, Risheng; Barrow, James C.; Snyder, Solomon H.

2015-01-01

The inositol pyrophosphates, molecular messengers containing an energetic pyrophosphate bond, impact a wide range of biologic processes. They are generated primarily by a family of three inositol hexakisphosphate kinases (IP6Ks), the principal product of which is diphosphoinositol pentakisphosphate (IP7). We report that IP6K2, via IP7 synthesis, is a major mediator of cancer cell migration and tumor metastasis in cell culture and in intact mice. IP6K2 acts by enhancing cell-matrix adhesion and decreasing cell–cell adhesion. This action is mediated by IP7-elicited nuclear sequestration and inactivation of the tumor suppressor liver kinase B1 (LKB1). Accordingly, inhibitors of IP6K2 offer promise in cancer therapy. PMID:25617365

Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections

NASA Astrophysics Data System (ADS)

Drebes, Julia; Künz, Madeleine; Windshügel, Björn; Kikhney, Alexey G.; Müller, Ingrid B.; Eberle, Raphael J.; Oberthür, Dominik; Cang, Huaixing; Svergun, Dmitri I.; Perbandt, Markus; Betzel, Christian; Wrenger, Carsten

2016-03-01

Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today known to be a substantial threat for global health. Emerging multi-drug resistant bacteria have created a substantial need to identify and discover new drug targets and to develop novel strategies to treat bacterial infections. A promising and so far untapped antibiotic target is the biosynthesis of vitamin B1 (thiamin). Thiamin in its activated form, thiamin pyrophosphate, is an essential co-factor for all organisms. Therefore, thiamin analogous compounds, when introduced into the vitamin B1 biosynthetic pathway and further converted into non-functional co-factors by the bacterium can function as pro-drugs which thus block various co-factor dependent pathways. We characterized one of the key enzymes within the S. aureus vitamin B1 biosynthetic pathway, 5-(hydroxyethyl)-4-methylthiazole kinase (SaThiM; EC 2.7.1.50), a potential target for pro-drug compounds and analyzed the native structure of SaThiM and complexes with the natural substrate 5-(hydroxyethyl)-4-methylthiazole (THZ) and two selected substrate analogues.

Thiamine pyrophosphate requirement for o-succinylbenzoic acid synthesis in Escherichia coli and evidence for an intermediate.

PubMed Central

Meganathan, R; Bentley, R

1983-01-01

Cell-free extracts of various strains of Escherichia coli synthesize the menaquinone biosynthetic intermediate o-succinylbenzoic acid (OSB) when supplied with chorismic acid, 2-ketoglutaric acid, and thiamine pyrophosphate (TPP). To assay for OSB synthesis, 2-[U-14C]ketoglutaric acid was used as substrate, and the synthesized OSB was examined by radiogas chromatography (as the dimethyl ester). [U-14C]Shikimic acid also gave rise to radioactive OSB if the cofactors necessary for enzymatic conversion to chorismic acid were added. Use of 2-[1-14C]ketoglutaric acid does not give rise to labeled OSB. In the absence of TPP during the incubations, OSB synthesis was much reduced; these observations are consistent with the proposed role for the succinic semialdehyde-TPP anion as the reagent adding to chorismic acid. Extracts of cells from menC and menD mutants did not form OSB separately, but did so in combination. There was evidence for formation of a product, X, by extracts of a menC mutant incubated with chorismic acid, TPP, and 2-ketoglutaric acid; X was converted to OSB by extracts of a menD mutant. It appears that the intermediate, X, is formed by one gene product and converted to OSB by the second gene product. PMID:6337125

The Conservation of Structure and Mechanism of Catalytic Action in a Family of Thiamin Pyrophosphate (TPP)-dependent Enzymes

NASA Technical Reports Server (NTRS)

Dominiak, P.; Ciszak, Ewa

2004-01-01

Thiamin pyrophosphate (TPP)-dependent enzymes are a divergent family of TPP and metal ion binding proteins that perform a wide range of functions with the common decarboxylation steps of a -(O=)C-C(OH)- fragment of alpha-ketoacids and alpha- hydroxyaldehydes. To determine how structure and catalytic action are conserved in the context of large sequence differences existing within this family of enzymes, we have carried out an analysis of TPP-dependent enzymes of known structures. The common structure of TPP-dependent enzymes is formed at the interface of four alpha/beta domains from at least two subunits, which provide for two metal and TPP-binding sites. Residues around these catalytic sites are conserved for functional purpose, while those further away from TPP are conserved for structural reasons. Together they provide a network of contacts required for flip-flop catalytic action within TPP-dependent enzymes. Thus our analysis defines a TPP-action motif that is proposed for annotating TPP-dependent enzymes for advancing functional proteomics.

Thiamine

MedlinePlus

... B vitamins, and found in many vitamin B complex products. Vitamin B complexes generally include vitamin B1 (thiamine), vitamin B2 (riboflavin), ... is required by our bodies to properly use carbohydrates. It also helps maintain proper nerve function.

Conservation of Fold and Topology of Functional Elements in Thiamin Pyrophosphate Enzymes

NASA Technical Reports Server (NTRS)

Dominiak, P.; Ciszak, E. M.

2005-01-01

Thiamin pyrophosphate (TPP)-dependent enzymes are a highly divergent family of proteins binding both TPP and metal ions. They perform decarboxylation-hydroxyaldehydes. Prior -ketoacids and of a common - (O=)C-C(OH)- fragment of to knowledge of three-dimensional structures of these enzmes, the GDGY25-30NN sequence was used to identify these enzymes. Subsequently, a number of structural studies on those enzymes revealed multi-subunit organization and the features of the two duplicate cofactor binding sites. Analyzing the structures of 44 structurally known enzymes, we found that the common structure of these enzymes is reduced to 180-220 amino acid long fragments of two PP and two PYR domains that form the [PP:PYR]2 binding center of two cofactor molecules. The structures of PP and PYR are arranged in a similar fold-sheet with triplets of helices on both sides.Dconsisting of a six-stranded Residues surrounding the cofactors are not strictly conserved, but they provide the same interatomic contacts required for the catalytic functions that these enzymes perform while maintaining interactive structural integrity. These structural and functional amino acids are topological counterparts located in the same positions of the conserved fold of sets of PP and PYR domains. Additional parallels include short fragments of sequences that link these amino acids to the fold and function. This report on the structural commonalities amongst TPP dependent enzymes is thought to contribute new approaches to annotation that may assist in advancing the functional proteomics of TPP dependent enzymes, and trace their complexity within evolutionary context.

Linking egg thiamine and fatty acid concentrations of Lake Michigan lake trout with early life stage mortality.

PubMed

Czesny, Sergiusz; Dettmers, John M; Rinchard, Jacques; Dabrowski, Konrad

2009-12-01

The natural reproduction of lake trout Salvelinus namaycush in Lake Michigan is thought to be compromised by nutritional deficiency associated with inadequate levels of thiamine (vitamin B1) in their eggs. However, mortality driven by thiamine deficiency (commonly referred to as early mortality syndrome [EMS]) is not the only significant cause of low lake trout survival at early life stages. In this study, we sought to better understand the combined effects of variable levels of thiamine and fatty acids in lake trout eggs on prehatch, posthatch, and swim-up-stage mortality. We sampled the eggs of 29 lake trout females from southwestern Lake Michigan. The concentrations of free thiamine and its vitamers (e.g., thiamine monophosphate [TMP] and thiamine pyrophosphate [TPP]) as well as fatty acid profiles were determined in sampled eggs. Fertilized eggs and embryos were monitored through the advanced swim-up stage (1,000 degree-days). Three distinct periods of mortality were identified: prehatch (0-400 degree-days), immediately posthatch (401-600 degree-days), and swim-up (601-1,000 degree-days). Stepwise multiple regression analysis revealed (1) that cis-7-hexadecenoic acid in both neutral lipids (NL) and phospholipids (PL) correlated with prehatch mortality, (2) that docosapentaenoic acid in PL and docosahexaenoic acid in NL correlated with posthatch mortality, and (3) that total lipids, TPP, and palmitoleic acid in NL, linoleic acid, and palmitic acid in PL correlated with the frequency of EMS. These results indicate the complexity of early life stage mortality in lake trout and suggest that inadequate levels of key fatty acids in eggs, along with variable thiamine content, contribute to the low survival of lake trout progeny in Lake Michigan.

Alternatives to vitamin B 1 uptake revealed with discovery of riboswitches in multiple marine eukaryotic lineages

DOE PAGES

McRose, Darcy; Guo, Jian; Monier, Adam; ...

2014-08-29

Here, vitamin B 1 (thiamine pyrophosphate, TPP) is essential to all life but scarce in ocean surface waters. In many bacteria and a few eukaryotic groups thiamine biosynthesis genes are controlled by metabolite-sensing mRNA-based gene regulators known as riboswitches. Using available genome sequences and transcriptomes generated from ecologically important marine phytoplankton, we identified 31 new eukaryotic riboswitches. These were found in alveolate, cryptophyte, haptophyte and rhizarian phytoplankton as well as taxa from two lineages previously known to have riboswitches (green algae and stramenopiles). The predicted secondary structures bear hallmarks of TPP-sensing riboswitches. Surprisingly, most of the identified riboswitches are affiliatedmore » with genes of unknown function, rather than characterized thiamine biosynthesis genes. Using qPCR and growth experiments involving two prasinophyte algae, we show that expression of these genes increases significantly under vitamin B 1-deplete conditions relative to controls. Pathway analyses show that several algae harboring the uncharacterized genes lack one or more enzymes in the known TPP biosynthesis pathway. We demonstrate that one such alga, the major primary producer Emiliania huxleyi, grows on 4-amino-5-hydroxymethyl-2-methylpyrimidine (a thiamine precursor moiety) alone, although long thought dependent on exogenous sources of thiamine. Thus, overall, we have identified riboswitches in major eukaryotic lineages not known to undergo this form of gene regulation. In these phytoplankton groups, riboswitches are often affiliated with widespread thiamine-responsive genes with as yet uncertain roles in TPP pathways. Further, taxa with ‘incomplete’ TPP biosynthesis pathways do not necessarily require exogenous vitamin B 1, making vitamin control of phytoplankton blooms more complex than the current paradigm suggests.« less

Alternatives to vitamin B 1 uptake revealed with discovery of riboswitches in multiple marine eukaryotic lineages

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

McRose, Darcy; Guo, Jian; Monier, Adam

Here, vitamin B 1 (thiamine pyrophosphate, TPP) is essential to all life but scarce in ocean surface waters. In many bacteria and a few eukaryotic groups thiamine biosynthesis genes are controlled by metabolite-sensing mRNA-based gene regulators known as riboswitches. Using available genome sequences and transcriptomes generated from ecologically important marine phytoplankton, we identified 31 new eukaryotic riboswitches. These were found in alveolate, cryptophyte, haptophyte and rhizarian phytoplankton as well as taxa from two lineages previously known to have riboswitches (green algae and stramenopiles). The predicted secondary structures bear hallmarks of TPP-sensing riboswitches. Surprisingly, most of the identified riboswitches are affiliatedmore » with genes of unknown function, rather than characterized thiamine biosynthesis genes. Using qPCR and growth experiments involving two prasinophyte algae, we show that expression of these genes increases significantly under vitamin B 1-deplete conditions relative to controls. Pathway analyses show that several algae harboring the uncharacterized genes lack one or more enzymes in the known TPP biosynthesis pathway. We demonstrate that one such alga, the major primary producer Emiliania huxleyi, grows on 4-amino-5-hydroxymethyl-2-methylpyrimidine (a thiamine precursor moiety) alone, although long thought dependent on exogenous sources of thiamine. Thus, overall, we have identified riboswitches in major eukaryotic lineages not known to undergo this form of gene regulation. In these phytoplankton groups, riboswitches are often affiliated with widespread thiamine-responsive genes with as yet uncertain roles in TPP pathways. Further, taxa with ‘incomplete’ TPP biosynthesis pathways do not necessarily require exogenous vitamin B 1, making vitamin control of phytoplankton blooms more complex than the current paradigm suggests.« less

Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon–carbon bond cleavage during α-oxidation of 3-methyl-branched fatty acids

PubMed Central

Foulon, Veerle; Antonenkov, Vasily D.; Croes, Kathleen; Waelkens, Etienne; Mannaerts, Guy P.; Van Veldhoven, Paul P.; Casteels, Minne

1999-01-01

In the third step of the α-oxidation of 3-methyl-branched fatty acids such as phytanic acid, a 2-hydroxy-3-methylacyl-CoA is cleaved into formyl-CoA and a 2-methyl-branched fatty aldehyde. The cleavage enzyme was purified from the matrix protein fraction of rat liver peroxisomes and identified as a protein made up of four identical subunits of 63 kDa. Its activity proved to depend on Mg2+ and thiamine pyrophosphate, a hitherto unrecognized cofactor of α-oxidation. Formyl-CoA and 2-methylpentadecanal were identified as reaction products when the purified enzyme was incubated with 2-hydroxy-3-methylhexadecanoyl-CoA as the substrate. Hence the enzyme catalyzes a carbon–carbon cleavage, and we propose calling it 2-hydroxyphytanoyl-CoA lyase. Sequences derived from tryptic peptides of the purified rat protein were used as queries to recover human expressed sequence tags from the databases. The composite cDNA sequence of the human lyase contained an ORF of 1,734 bases that encodes a polypeptide with a calculated molecular mass of 63,732 Da. Recombinant human protein, expressed in mammalian cells, exhibited lyase activity. The lyase displayed homology to a putative Caenorhabditis elegans protein that resembles bacterial oxalyl-CoA decarboxylases. Similarly to the decarboxylases, a thiamine pyrophosphate-binding consensus domain was present in the C-terminal part of the lyase. Although no peroxisome targeting signal, neither 1 nor 2, was apparent, transfection experiments with constructs encoding green fluorescent protein fused to the full-length lyase or its C-terminal pentapeptide indicated that the C terminus of the lyase represents a peroxisome targeting signal 1 variant. PMID:10468558

Effect of sample handling on thiamine and thiaminolytic activity in alewife

USGS Publications Warehouse

Wright, G.M.; Brown, S.B.; Brown, L.R.; Moore, K.; Villella, M.; Zajicek, J.L.; Tillitt, D.E.; Fitzsimons, J.D.; Honeyfield, D.C.

2005-01-01

Alewives Alosa pseudoharengus were collected to evaluate handling and processing conditions that may affect the measurement of their thiamine-thiaminase content. Fish were captured by otter trawl, and reference samples of live fish were quick-frozen on dry ice immediately following capture. Other samples were placed on wet ice (4??C) or held in ambient lake water (21.5??C) for periods of up to 5 h before freezing. Total thiamine levels for reference samples averaged 26 nmol/g and consisted of 66, 15, and 19% thiamine pyrophosphate (TPP), thiamine monophosphate (TMP), and unphosphorylated thiamine (Th), respectively. After 120 min at either 4??C or 21.5??C, total thiamine concentrations were lower. At 21.5??C, the TPP proportion had decreased by 30 min and the proportion as Th increased after 60 min. In the groups sampled after 5 h, total thiamine concentrations were not altered but the proportion of TPP was lower and that of Th was higher than in reference samples. The stability of thiamine in thawed muscle samples from previously frozen alewives was poor (40% loss by 1 h at 22??C and 30% loss by 2 h at 4??C). Thiaminase activity averaged 5,975 pmol??g wet weight -1??min-1 in reference samples. In fresh-caught alewives, thiaminase activities were remarkably consistent throughout the sampling period. At 4??C, thiaminase activity in muscle tissue from previously frozen alewives was stable for the entire investigation period. At 25??C, the activity initially increased by 40% after 60 min but then decreased to 50% of initial value after 5 h. We conclude that sampling times greater than 25 min could cause some changes in the various thiamine forms and net loss in total thiamine. The thiamine content in previously frozen alewife samples is highly labile, requiring low temperatures during processing for analysis. ?? Copyright by the American Fisheries Society 2005.

In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush)

USGS Publications Warehouse

Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

2014-01-01

In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP – biologically inactive form) to thiamine pyrophosphate (TPP – biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state.

In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush).

PubMed

Ottinger, Christopher A; Honeyfield, Dale C; Densmore, Christine L; Iwanowicz, Luke R

2014-05-01

In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP--biologically inactive form) to thiamine pyrophosphate (TPP--biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state. Published by Elsevier Ltd.

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5878 - Thiamine mononitrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5878 Thiamine mononitrate. (a) Product. Thiamine mononitrate. (b) Conditions of use. This...

21 CFR 582.5878 - Thiamine mononitrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5878 Thiamine mononitrate. (a) Product. Thiamine mononitrate. (b) Conditions of use. This...

21 CFR 582.5878 - Thiamine mononitrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5878 Thiamine mononitrate. (a) Product. Thiamine mononitrate. (b) Conditions of use. This...

Radiolysis of aqueous solutions of thiamine

NASA Astrophysics Data System (ADS)

Chijate, C.; Albarran, G.; Negron-Mendoza, A.

1998-06-01

The results of the radiolysis of aqueous solutions of thiamine (vitamin B 1) are presented. The yields for decomposition of thiamine and the product of radiolytic products were determined. The G values decrease as the dose increases. Some radiolytic products were identified. Decomposition of thiamine was slightly dependent on the presence of oxygen and on the pH of the solution. At pH 4.4 with a concentration of 2.5 × 10 -4 mol L -1 of thiamine in an oxygen free aqueous solution, the G 0 value for decomposition is 5.0.

Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1)

PubMed Central

Al-Daghri, Nasser M; Alharbi, Mohammed; Wani, Kaiser; Abd-Alrahman, Sherif H; Sheshah, Eman; Alokail, Majed S

2015-01-01

Thiamine (vitamin B1) is an essential enzyme cofactor in most organisms required at several stages of anabolic and catabolic intermediary metabolism. However, little is known on the positive effects of thiamine in diabetic type 1 (DMT1) patients. The objectives of this study were to evaluate the biochemical changes related to thiamine deficiency in patients with DMT1 outcomes among Saudi adults. We hypothesized that blood thiamine deficiency in patients with DMT1 manifestations might lead to an increase in metabolic syndrome. A total of 77 patients with DMT1 (age 35.8±5.5) and 81 controls (age 45.0±18.1) (total N = 158) were randomly selected from the Riyadh Cohort Study for inclusion. Saudi adults with diabetes type 1, a significant decrease in systolic (P < 0.001), and diastolic blood pressure (P = 0.008) and microalbuminuria (P = 0.02). Moreover, cholesterol, glucose and triglycerides were significantly increased (P 0.001, 0.001 and 0.008, respectively) in patients with diabetes type 1 compared to controls. On the other hand, HDL, TMP, TDP and thiamine, were significantly decreased in patients with diabetes type 1 (P 0.005, 0.002, 0.005, and 0.002), respectively. A strong association between blood thiamine level and diabetes type 1 was detected in our study population. The results confirmed the role of thiamine and thiamine phosphate esters, in preventing metabolic changes and complications of diabetes type 1. The levels of these thiamine and thiamine phosphate esters were correlated with diabetes related biomarkers including HDL, glucose, triglycerides and cholesterol, as well as microalbuminuria, LDL and urine thiamine. The results support a pivotal role of blood thiamine and its phosphate esters in preventing the biochemical changes and complications in patients with DMT1. PMID:26722561

Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1).

PubMed

Al-Daghri, Nasser M; Alharbi, Mohammed; Wani, Kaiser; Abd-Alrahman, Sherif H; Sheshah, Eman; Alokail, Majed S

2015-01-01

Thiamine (vitamin B1) is an essential enzyme cofactor in most organisms required at several stages of anabolic and catabolic intermediary metabolism. However, little is known on the positive effects of thiamine in diabetic type 1 (DMT1) patients. The objectives of this study were to evaluate the biochemical changes related to thiamine deficiency in patients with DMT1 outcomes among Saudi adults. We hypothesized that blood thiamine deficiency in patients with DMT1 manifestations might lead to an increase in metabolic syndrome. A total of 77 patients with DMT1 (age 35.8 ± 5.5) and 81 controls (age 45.0 ± 18.1) (total N = 158) were randomly selected from the Riyadh Cohort Study for inclusion. Saudi adults with diabetes type 1, a significant decrease in systolic (P < 0.001), and diastolic blood pressure (P = 0.008) and microalbuminuria (P = 0.02). Moreover, cholesterol, glucose and triglycerides were significantly increased (P 0.001, 0.001 and 0.008, respectively) in patients with diabetes type 1 compared to controls. On the other hand, HDL, TMP, TDP and thiamine, were significantly decreased in patients with diabetes type 1 (P 0.005, 0.002, 0.005, and 0.002), respectively. A strong association between blood thiamine level and diabetes type 1 was detected in our study population. The results confirmed the role of thiamine and thiamine phosphate esters, in preventing metabolic changes and complications of diabetes type 1. The levels of these thiamine and thiamine phosphate esters were correlated with diabetes related biomarkers including HDL, glucose, triglycerides and cholesterol, as well as microalbuminuria, LDL and urine thiamine. The results support a pivotal role of blood thiamine and its phosphate esters in preventing the biochemical changes and complications in patients with DMT1.

21 CFR 582.5223 - Calcium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...

21 CFR 582.5223 - Calcium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...

21 CFR 582.5223 - Calcium pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...

21 CFR 582.5223 - Calcium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...

21 CFR 582.5223 - Calcium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...

21 CFR 582.5304 - Ferric pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...

21 CFR 582.5304 - Ferric pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...

21 CFR 582.5304 - Ferric pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...

21 CFR 582.5304 - Ferric pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...

21 CFR 582.5304 - Ferric pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...

Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells

PubMed Central

Wang, Hong; Morita, Craig T.

2016-01-01

Vγ2Vδ2 T cells play important roles in human immunity to pathogens and in cancer immunotherapy by responding to isoprenoid metabolites, such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and isopentenyl pyrophosphate. The Ig superfamily protein butyrophilin (BTN)3A1 was shown to be required for prenyl pyrophosphate stimulation. We proposed that the intracellular B30.2 domain of BTN3A1 binds prenyl pyrophosphates, resulting in a change in the extracellular BTN3A1 dimer that is detected by Vγ2Vδ2 TCRs. Such B30.2 binding was demonstrated recently. However, other investigators reported that the extracellular BTN3A1 IgV domain binds prenyl pyrophosphates, leading to the proposal that the Vγ2Vδ2 TCR recognizes the complex. To distinguish between these mechanisms, we mutagenized residues in the two binding sites and tested the mutant BTN3A1 proteins for their ability to mediate prenyl pyrophosphate stimulation of Vγ2Vδ2 T cells to proliferate and secrete TNF-α. Mutagenesis of residues in the IgV site had no effect on Vγ2Vδ2 T cell proliferation or secretion of TNF-α. In contrast, mutagenesis of residues within the basic pocket and surrounding V regions of the B30.2 domain abrogated prenyl pyrophosphate-induced proliferation. Mutations of residues making hydrogen bonds to the pyrophosphate moiety also abrogated TNF-α secretion, as did mutation of aromatic residues making contact with the alkenyl chain. Some mutations further from the B30.2 binding site also diminished stimulation, suggesting that the B30.2 domain may interact with a second protein. These findings support intracellular sensing of prenyl pyrophosphates by BTN3A1 rather than extracellular presentation. PMID:26475929

Thiamine and magnesium deficiencies: keys to disease.

PubMed

Lonsdale, D

2015-02-01

Thiamine deficiency (TD) is accepted as the cause of beriberi because of its action in the metabolism of simple carbohydrates, mainly as the rate limiting cofactor for the dehydrogenases of pyruvate and alpha-ketoglutarate, both being critical to the action of the citric acid cycle. Transketolase, dependent on thiamine and magnesium, occurs twice in the oxidative pentose pathway, important in production of reducing equivalents. Thiamine is also a cofactor in the dehydrogenase complex in the degradation of the branched chain amino acids, leucine, isoleucine and valine. In spite of these well accepted facts, the overall clinical effects of TD are still poorly understood. Because of the discovery of 2-hydroxyacyl-CoA lyase (HACL1) as the first peroxisomal enzyme in mammals found to be dependent on thiamine pyrophosphate (TPP) and the ability of thiamine to bind with prion protein, these factors should improve our clinical approach to TD. HACL1 has two important roles in alpha oxidation, the degradation of phytanic acid and shortening of 2-hydroxy long-chain fatty acids so that they can be degraded further by beta oxidation. The downstream effects of a lack of efficiency in this enzyme would be expected to be critical in normal brain metabolism. Although TD has been shown experimentally to produce reversible damage to mitochondria and there are many other causes of mitochondrial dysfunction, finding TD as the potential biochemical lesion would help in differential diagnosis. Stresses imposed by infection, head injury or inoculation can initiate intermittent cerebellar ataxia in thiamine deficiency/dependency. Medication or vaccine reactions appear to be more easily initiated in the more intelligent individuals when asymptomatic marginal malnutrition exists. Erythrocyte transketolase testing has shown that thiamine deficiency is widespread. It is hypothesized that the massive consumption of empty calories, particularly those derived from carbohydrate and fat, results in

Impact of thiamine deficiency on T-cell dependent and T-cell independent antibody production in lake trout

USGS Publications Warehouse

Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

2012-01-01

Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets were evaluated for the effects of thiamine status on in vivo responses to the T-dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T-independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's phosphate-buffered saline (DPBS; negative control fish). Plasma antibody concentrations were evaluated for possible differences in total anti-TNP activity as well as differences in response kinetics. Associations between anti-TNP activity and muscle and liver thiamine concentrations as well as ratios of muscle-to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake trout that were injected with TNP-LPS exhibited significantly more anti-TNP activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also exhibited significantly different response kinetics relative to thiamine-replete lake trout. No differences in activity or kinetics were observed between the thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH was positively associated with muscle thiamine pyrophosphate (thiamine diphosphate; TPP) concentration. A negative association was observed between the ratio of muscle-to-liver TPP and T-independent responses. No significant associations between anti-TNP activity and tissue thiamine concentration were observed in the thiamine-replete fish. We demonstrated that thiamine deficiency leads to alterations in both T-dependent and T-independent immune responses in lake trout.

Impact of thiamine deficiency on T-cell dependent and T-cell independent antibody production in lake trout.

PubMed

Ottinger, Christopher A; Honeyfield, Dale C; Densmore, Christine L; Iwanowicz, Luke R

2012-12-01

Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets were evaluated for the effects of thiamine status on in vivo responses to the T-dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T-independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's phosphate-buffered saline (DPBS; negative control fish). Plasma antibody concentrations were evaluated for possible differences in total anti-TNP activity as well as differences in response kinetics. Associations between anti-TNP activity and muscle and liver thiamine concentrations as well as ratios of muscle-to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake trout that were injected with TNP-LPS exhibited significantly more anti-TNP activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also exhibited significantly different response kinetics relative to thiamine-replete lake trout. No differences in activity or kinetics were observed between the thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH was positively associated with muscle thiamine pyrophosphate (thiamine diphosphate; TPP) concentration. A negative association was observed between the ratio of muscle-to-liver TPP and T-independent responses. No significant associations between anti-TNP activity and tissue thiamine concentration were observed in the thiamine-replete fish. We demonstrated that thiamine deficiency leads to alterations in both T-dependent and T-independent immune responses in lake trout.

21 CFR 582.5306 - Ferric sodium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5306 Ferric sodium pyrophosphate. (a) Product. Ferric sodium pyrophosphate. (b...

21 CFR 182.6789 - Tetra sodium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Tetra sodium pyrophosphate. 182.6789 Section 182...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when...

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

PubMed

Naito, E; Ito, M; Yokota, I; Saijo, T; Matsuda, J; Osaka, H; Kimura, S; Kuroda, Y

1997-08-01

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

Radiation damage in vitamin B 1: An endor study of an x-irradiated single crystal of thiamine

NASA Astrophysics Data System (ADS)

Geoffroy, M.; Reddy, M. V. V. S.; Lambelet, P.; Horman, I.

A single crystal of thiamine chloride hydrochloride has been x-irradiated at room temperature and studied by 1H-ENDOR spectroscopy at 110 K. It is shown that at least two radical species are trapped in the crystal. Several 1H-hyperfine tensors have been determined for each radical; they indicate that one species is due to cleavage of the thiamine molecule into its pyrimidine and thiazole moieties while the other species is due to hydrogen addition onto the pyrimidine ring.

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

PubMed Central

Balk, Lennart; Hägerroth, Per-Åke; Gustavsson, Hanna; Sigg, Lisa; Åkerman, Gun; Ruiz Muñoz, Yolanda; Honeyfield, Dale C.; Tjärnlund, Ulla; Oliveira, Kenneth; Ström, Karin; McCormick, Stephen D.; Karlsson, Simon; Ström, Marika; van Manen, Mathijs; Berg, Anna-Lena; Halldórsson, Halldór P.; Strömquist, Jennie; Collier, Tracy K.; Börjeson, Hans; Mörner, Torsten; Hansson, Tomas

2016-01-01

Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported. PMID:27958327

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

USGS Publications Warehouse

Balk, Lennart; Hägerroth, Per-Åke; Gustavsson, Hanna; Sigg, Lisa; Akerman, Gun; Ruiz Muñoz, Yolanda; Honeyfield, Dale C.; Tjarnlund, Ulla; Oliveira, Kenneth; Strom, Karin; McCormick, Stephen D.; Karlsson, Simon; Strom, Marika; van Manen, Mathijs; Berg, Anna-Lena; Halldórsson, Halldór P.; Stromquist, Jennie; Collier, Tracy K.; Borjeson, Hans; Morner, Torsten; Hansson, Tomas

2016-01-01

Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

NASA Astrophysics Data System (ADS)

Balk, Lennart; Hägerroth, Per-Åke; Gustavsson, Hanna; Sigg, Lisa; Åkerman, Gun; Ruiz Muñoz, Yolanda; Honeyfield, Dale C.; Tjärnlund, Ulla; Oliveira, Kenneth; Ström, Karin; McCormick, Stephen D.; Karlsson, Simon; Ström, Marika; van Manen, Mathijs; Berg, Anna-Lena; Halldórsson, Halldór P.; Strömquist, Jennie; Collier, Tracy K.; Börjeson, Hans; Mörner, Torsten; Hansson, Tomas

2016-12-01

Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291).

PubMed

Sabui, Subrata; Subramanian, Veedamali S; Kapadia, Rubina; Said, Hamid M

2016-08-01

Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier-mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model ("Phyre2" and "DockingServer") to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted ("PRALINE") to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were found to be critical for function. While no change in translational efficiency/protein stability of the Ser(34) mutant was observed, both the Ile(33) and Asp(37) mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His(82), His(137), Lys(231) and Lys(291)) predicted in the TMD showed that His(137) and Lys(291) are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT. Copyright © 2016 Elsevier B.V. All rights reserved.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

PubMed

Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

2016-09-01

Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...

21 CFR 582.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...

21 CFR 182.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...

21 CFR 582.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...

21 CFR 182.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...

21 CFR 182.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...

21 CFR 182.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...

21 CFR 582.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...

21 CFR 582.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...

21 CFR 582.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...

Delayed Language Development Due to Infantile Thiamine Deficiency

ERIC Educational Resources Information Center

Fattal-Valevski, Aviva; Azouri-Fattal, Iris; Greenstein, Yoram J.; Guindy, Michal; Blau, Ayala; Zelnik, Nathanel

2009-01-01

The aim of this study was to investigate the language development of 20 children who had been exposed to thiamine (vitamin B[subscript 1]) deficiency in infancy due to feeding with soy-based formula that was accidentally deficient of thiamine. In this case-control study, 20 children (12 males, eight females; mean age 31.8 mo [SD 4.1], range 24-39…

Vitamin B1 Functions as an Activator of Plant Disease Resistance1

PubMed Central

Ahn, Il-Pyung; Kim, Soonok; Lee, Yong-Hwan

2005-01-01

Vitamin B1 (thiamine) is an essential nutrient for humans. Vitamin B1 deficiency causes beriberi, which disturbs the central nervous and circulatory systems. In countries in which rice (Oryza sativa) is a major food, thiamine deficiency is prevalent because polishing of rice removes most of the thiamine in the grain. We demonstrate here that thiamine, in addition to its nutritional value, induces systemic acquired resistance (SAR) in plants. Thiamine-treated rice, Arabidopsis (Arabidopsis thaliana), and vegetable crop plants showed resistance to fungal, bacterial, and viral infections. Thiamine treatment induces the transient expression of pathogenesis-related (PR) genes in rice and other plants. In addition, thiamine treatment potentiates stronger and more rapid PR gene expression and the up-regulation of protein kinase C activity. The effects of thiamine on disease resistance and defense-related gene expression mobilize systemically throughout the plant and last for more than 15 d after treatment. Treatment of Arabidopsis ecotype Columbia-0 plants with thiamine resulted in the activation of PR-1 but not PDF1.2. Furthermore, thiamine prevented bacterial infection in Arabidopsis mutants insensitive to jasmonic acid or ethylene but not in mutants impaired in the SAR transduction pathway. These results clearly demonstrate that thiamine induces SAR in plants through the salicylic acid and Ca2+-related signaling pathways. The findings provide a novel paradigm for developing alternative strategies for the control of plant diseases. PMID:15980201

Whole cell immobilized amperometric biosensor based on Saccharomyces cerevisiae for selective determination of vitamin B1 (thiamine).

PubMed

Akyilmaz, Erol; Yaşa, Ihsan; Dinçkaya, Erhan

2006-07-01

A new amperometric whole cell biosensor based on Saccharomyces cerevisiae immobilized in gelatin was developed for selective determination of vitamin B1 (thiamine). The biosensor was constructed by using gelatin and crosslinking agent glutaraldehyde to immobilize S. cerevisiae cells on the Teflon membrane of dissolved oxygen (DO) probe used as the basic electrode system combined with a digital oxygen meter. The cells were induced by vitamin B1 in the culture medium, and the cells used it as a carbon source in the absence of glucose. So, when the vitamin B1 solution is injected into the whole cell biosensor system, an increase in respiration activity of the cells results from the metabolic activity and causes a decrease in the DO concentration of interval surface of DO probe related to vitamin B1 concentration. The response time of the biosensor is 3 min, and the optimal working conditions of the biosensor were carried out as pH 7.0, 50mM Tris-HCl, and 30 degrees C. A linear relationship was obtained between the DO concentration decrease and vitamin B1 concentration between 5.0 x 10(-3) and 10(-1) microM. In the application studies of the biosensor, sensitive determination of vitamin B1 in the vitamin tablets was investigated.

Structural Basis for Flip-Flop Action of Thiamin Pyrophosphate-Dependent Enzymes Revealed by Human Pyruvate Dehydrogenase

NASA Technical Reports Server (NTRS)

Dominiak, Paulina; Ciszak, Ewa M.; Korotchkina, Lioubov; Sidhu, Sukhdeep; Patel, Mulchand

2003-01-01

Thiamin pyrophosphate (TPP), the biologically active form of vitamin BI, is a cofactor of enzymes catalyzing reactions involving the cleavage of a carbon-carbon bond adjacent to an oxo group. TPP-dependent enzymes show a common mechanism of TPP activation by: (1) forming the ionic N-H...O(sup -) hydrogen bonding between the N1' atom of the aminopirymidine ring of the coenzyme and intrinsic gamma-carboxylate group of glutamate and (2) imposing an "active" V-conformation that brings the N4' atom of the aminopirymidine to the distance required for the intramolecular C-H.. .N hydrogen bonding with the thiazolium C2 atom. Within these two hydrogen bonds that rapidly exchange protons, protonation of the N1' atom is strictly coordinated with the deprotonation of the 4' -amino group and eventually abstraction of the proton from C2. The human pyruvate dehydrogenase Elp, component of human pyruvate dehydrogenase complex, catalyzes the irreversible decarboxylation of the pyruvate followed by the reductive acetylation of the lipoyl group of dihydrolipoyl acyltransferase. Elp is alpha(sub 2)beta(sub2)-heterotetrameric with a molecular mass of I54 kDa, which has two catalytic sites, each providing TPP and magnesium ion as cofactors and each formed on the interface between the PP and PYR domains. The dynamic nonequivalence of two otherwise chemically equivalent catalytic sites has been observed and the flip-flop mechanism was suggested, according to which two active sites affect each other and in which different steps of the catalytic reaction are performed in each of the sites at any given moment. Based on specific futures of human pyruvate dehydrogenase including rigid and flexible connections between domains that bind the cofactor we propose a mechanistic model for the flip-flop action of this enzyme. We postulate that the dynamic protein environment drives the exchange of tautomers in the 4' -aminopyrimidine ring of the cofactor through a concerted shuttl-like motion of

Thiamine-responsive megaloblastic anemia: early diagnosis may be effective in preventing deafness.

PubMed

Onal, Hasan; Bariş, Safa; Ozdil, Mine; Yeşil, Gözde; Altun, Gürkan; Ozyilmaz, Isa; Aydin, Ahmet; Celkan, Tiraje

2009-01-01

Thiamine-responsive megaloblastic anemia syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss. Mutations in the SLC19A2 gene, encoding a high-affinity thiamine transporter protein, THTR-1, are responsible for the clinical features associated with thiamine-responsive megaloblastic anemia syndrome in which treatment with pharmacological doses of thiamine correct the megaloblastic anemia and diabetes mellitus. The anemia can recur when thiamine is withdrawn. Thiamine may be effective in preventing deafness if started before two months. Our patient was found homozygous for a mutation, 242insA, in the nucleic acid sequence of exon B, with insertion of an adenine introducing a stop codon at codon 52 in the high-affinity thiamine transporter gene, SLC19A2, on chromosome 1q23.3.

Maternal consumption of thiamin-fortified fish sauce during pregnancy and lactation improves maternal and infant thiamin status and breast milk thiamin concentrations.

USDA-ARS?s Scientific Manuscript database

Infantile beriberi, a disease caused by thiamin (vitamin B1) deficiency, remains a public health concern in Cambodia and other parts of Southeast Asia. Infantile beriberi presents during the exclusive breastfeeding period and without treatment commonly results in death within *24 hours of clinical p...

21 CFR 182.6789 - Tetra sodium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tetra sodium pyrophosphate. 182.6789 Section 182.6789 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This...

21 CFR 182.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...

21 CFR 182.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally...

21 CFR 582.6789 - Tetra sodium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tetra sodium pyrophosphate. 582.6789 Section 582.6789 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This...

21 CFR 182.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...

21 CFR 182.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...

Overexpression of Thiamin Biosynthesis Genes in Rice Increases Leaf and Unpolished Grain Thiamin Content But Not Resistance to Xanthomonas oryzae pv. oryzae

PubMed Central

Dong, Wei; Thomas, Nicholas; Ronald, Pamela C.; Goyer, Aymeric

2016-01-01

Thiamin diphosphate (ThDP), also known as vitamin B1, serves as an enzymatic cofactor in glucose metabolism, the Krebs cycle, and branched-chain amino acid biosynthesis in all living organisms. Unlike plants and microorganisms, humans are not able to synthesize ThDP de novo and must obtain it from their diet. Staple crops such as rice are poor sources of thiamin. Hence, populations that mainly consume rice commonly suffer thiamin deficiency. In addition to thiamin’s nutritional function, studies in rice have shown that some thiamin biosynthesis genes are involved in resistance to Xanthomonas oryzae, which causes a serious disease in rice fields. This study shows that overexpression of two thiamin biosynthesis genes, 4-methyl-5-β-hydroxyethylthiazole phosphate synthase and 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate synthase, involved in the first steps of the thiazole and pyrimidine synthesis branches, respectively, increased thiamin content up to fivefold in unpolished seeds that retain the bran. However, thiamin levels in polished seeds with removed bran were similar to those found in polished control seeds. Plants with higher accumulation of thiamin did not show enhanced resistance to X. oryzae. These results indicate that stacking of two traits can enhance thiamin accumulation in rice unpolished grain. We discuss potential roadblocks that prevent thiamin accumulation in the endosperm. PMID:27242822

The route of non-enzymic and enzymic breakdown of 5-phosphoribosyl 1-pyrophosphate to ribose 1-phosphate.

PubMed Central

Trembacz, H; Jezewska, M M

1990-01-01

Spontaneous decomposition of 5-phosphoribosyl 1-pyrophosphate at pH 5.5 was established to occur as follows: 5-Phosphoribosyl 1-pyrophosphate----5-phosphoribosyl 1,2-(cyclic)phosphate----ribose 1-phosphate----ribose Enzymic degradation of 5-phosphoribosyl 1-pyrophosphate by alkaline phosphatase from calf intestine and by acid phosphatases from potato and Aspergillus niger was found to proceed according to this pathway within the pH range 2.5-7.4 with accumulation of ribose 1-phosphate. In the case of alkaline phosphatase, Mg2+ ions inhibit the pyrophosphorolysis of 5-phosphoribosyl 1-pyrophosphate and stimulate the hydrolysis of ribose 1-phosphate. PMID:1700897

21 CFR 582.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

21 CFR 582.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

21 CFR 582.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

21 CFR 582.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

21 CFR 582.1087 - Sodium acid pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

Effectiveness of egg immersion in aqueous solutions of thiamine and thiamine analogs for reducing early mortality syndrome

USGS Publications Warehouse

Brown, S.B.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Williston, B.; Honeyfield, D.C.; Hinterkopf, J.P.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.

2005-01-01

Protocols used for therapeutic thiamine treatments in salmonine early mortality syndrome (EMS) were investigated in lake trout Salvelinus namaycush and coho salmon Oncorhynchus kisutch to assess their efficacy. At least 500 mg of thiamine HCl/L added to egg baths was required to produce a sustained elevation of thiamine content in lake trout eggs. Thiamine uptake from egg baths was not influenced by a pH ranging from 5.5 to 7.5 or by a water hardness between 2 and 200 mg CaCO3/L. There was poorer thiamine uptake when initial thiamine levels were low, suggesting that current treatment regimes may not be as effective when thiamine levels are severely depressed and that higher treatment doses are necessary. Exposure of eggs to the more lipid-soluble thiamine analog allithiamine (1,000 mg/L) during water hardening increased egg thiamine levels by 1.5-2.5 nmol/g and was completely effective at reversing EMS. Another more lipid-soluble thiamine analog, benfotiamine (100 mg/L), reduced EMS but did not produce detectable increases in egg thiamine content. Although benfotiamine may be more effective than thiamine at mitigating EMS, it is more expensive than thiamine HCl or allithiamine. In addition, there still needs to be a more thorough examination of dose-response relationships. We conclude that allithiamine is an alternative to the use of thiamine in egg baths as a therapeutic treatment for salmonid EMS. ?? Copyright by the American Fisheries Society 2005.

The effect of thiamine injection on upstream migration, survival, and thiamine status of putative thiamine-deficient coho salmon

USGS Publications Warehouse

Fitzsimons, J.D.; Williston, B.; Amcoff, P.; Balk, L.; Pecor, C.; Ketola, H.G.; Hinterkopf, J.P.; Honeyfield, D.C.

2005-01-01

A diet containing a high proportion of alewives Alosa pseudoharengus results in a thiamine deficiency that has been associated with high larval salmonid mortality, known as early mortality syndrome (EMS), but relatively little is known about the effects of the deficiency on adults. Using thiamine injection (50 mg thiamine/kg body weight) of ascending adult female coho salmon Oncorhynchus kisutch on the Platte River, Michigan, we investigated the effects of thiamine supplementation on migration, adult survival, and thiamine status. The thiamine concentrations of eggs, muscle (red and white), spleen, kidney (head and trunk), and liver and the transketolase activity of the liver, head kidney, and trunk kidney of fish injected with thiamine dissolved in physiological saline (PST) or physiological saline only (PS) were compared with those of uninjected fish. The injection did not affect the number of fish making the 15-km upstream migration to a collection weir but did affect survival once fish reached the upstream weir, where survival of PST-injected fish was almost twice that of controls. The egg and liver thiamine concentrations in PS fish sampled after their upstream migration were significantly lower than those of uninjected fish collected at the downstream weir, but the white muscle thiamine concentration did not differ between the two groups. At the upper weir, thiamine levels in the liver, spleen, head kidney, and trunk kidney of PS fish were indistinguishable from those of uninjected fish (called "wigglers") suffering from a severe deficiency and exhibiting reduced equilibrium, a stage that precedes total loss of equilibrium and death. For PST fish collected at the upstream weir, total thiamine levels in all tissues were significantly elevated over those of PS fish. Based on the limited number of tissues examined, thiamine status was indicated better by tissue thiamine concentration than by transketolase activity. The adult injection method we used appears to

A thiamin-utilizing ribozyme decarboxylates a pyruvate-like substrate

NASA Astrophysics Data System (ADS)

Cernak, Paul; Sen, Dipankar

2013-11-01

Vitamins are hypothesized to be relics of an RNA world, and were probably participants in RNA-mediated primordial metabolism. If catalytic RNAs, or ribozymes, could harness vitamin cofactors to aid their function in a manner similar to protein enzymes, it would enable them to catalyse a much larger set of chemical reactions. The cofactor thiamin diphosphate, a derivative of vitamin B1 (thiamin), is used by enzymes to catalyse difficult metabolic reactions, including decarboxylation of stable α-keto acids such as pyruvate. Here, we report a ribozyme that uses free thiamin to decarboxylate a pyruvate-based suicide substrate (LnkPB). Thiamin conjugated to biotin was used to isolate catalytic individuals from a pool of random-sequence RNAs attached to LnkPB. Analysis of a stable guanosine adduct obtained via digestion of an RNA sequence (clone dc4) showed the expected decarboxylation product. The discovery of a prototypic thiamin-utilizing ribozyme has implications for the role of RNA in orchestrating early metabolic cycles.

The Drosophila melanogaster Gut Microbiota Provisions Thiamine to Its Host

PubMed Central

2018-01-01

ABSTRACT The microbiota of Drosophila melanogaster has a substantial impact on host physiology and nutrition. Some effects may involve vitamin provisioning, but the relationships between microbe-derived vitamins, diet, and host health remain to be established systematically. We explored the contribution of microbiota in supplying sufficient dietary thiamine (vitamin B1) to support D. melanogaster at different stages of its life cycle. Using chemically defined diets with different levels of available thiamine, we found that the interaction of thiamine concentration and microbiota did not affect the longevity of adult D. melanogaster. Likewise, this interplay did not have an impact on egg production. However, we determined that thiamine availability has a large impact on offspring development, as axenic offspring were unable to develop on a thiamine-free diet. Offspring survived on the diet only when the microbiota was present or added back, demonstrating that the microbiota was able to provide enough thiamine to support host development. Through gnotobiotic studies, we determined that Acetobacter pomorum, a common member of the microbiota, was able to rescue development of larvae raised on the no-thiamine diet. Further, it was the only microbiota member that produced measurable amounts of thiamine when grown on the thiamine-free fly medium. Its close relative Acetobacter pasteurianus also rescued larvae; however, a thiamine auxotrophic mutant strain was unable to support larval growth and development. The results demonstrate that the D. melanogaster microbiota functions to provision thiamine to its host in a low-thiamine environment. PMID:29511074

Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls.

PubMed

Anwar, Attia; Marini, Marina; Abruzzo, Provvidenza Maria; Bolotta, Alessandra; Ghezzo, Alessandro; Visconti, Paola; Thornalley, Paul J; Rabbani, Naila

2016-11-01

To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage. 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined. Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged. Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis.

Heightened Avidity for Trisodium Pyrophosphate in Mice Lacking Tas1r3

PubMed Central

Aleman, Tiffany R.; McCaughey, Stuart A.

2015-01-01

Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6–56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8–56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. PMID:25452580

Globally Important Haptophyte Algae Use Exogenous Pyrimidine Compounds More Efficiently than Thiamin

PubMed Central

Gutowska, Magdalena A.; Shome, Brateen; Sudek, Sebastian; McRose, Darcy L.; Hamilton, Maria; Giovannoni, Stephen J.; Begley, Tadhg P.

2017-01-01

ABSTRACT Vitamin B1 (thiamin) is a cofactor for critical enzymatic processes and is scarce in surface oceans. Several eukaryotic marine algal species thought to rely on exogenous thiamin are now known to grow equally well on the precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP), including the haptophyte Emiliania huxleyi. Because the thiamin biosynthetic capacities of the diverse and ecologically important haptophyte lineage are otherwise unknown, we investigated the pathway in transcriptomes and two genomes from 30 species representing six taxonomic orders. HMP synthase is missing in data from all studied taxa, but the pathway is otherwise complete, with some enzymatic variations. Experiments on axenic species from three orders demonstrated that equivalent growth rates were supported by 1 µM HMP or thiamin amendment. Cellular thiamin quotas were quantified in the oceanic phytoplankter E. huxleyi using the thiochrome assay. E. huxleyi exhibited luxury storage in standard algal medium [(1.16 ± 0.18) × 10−6 pmol thiamin cell−1], whereas quotas in cultures grown under more environmentally relevant thiamin and HMP supplies [(2.22 ± 0.07) × 10−7 or (1.58 ± 0.14) × 10−7 pmol thiamin cell−1, respectively] were significantly lower than luxury values and prior estimates. HMP and its salvage-related analog 4-amino-5-aminomethyl-2-methylpyrimidine (AmMP) supported higher growth than thiamin under environmentally relevant supply levels. These compounds also sustained growth of the stramenopile alga Pelagomonas calceolata. Together with identification of a salvage protein subfamily (TENA_E) in multiple phytoplankton, the results indicate that salvaged AmMP and exogenously acquired HMP are used by several groups for thiamin production. Our studies highlight the potential importance of thiamin pathway intermediates and their analogs in shaping phytoplankton community structure. PMID:29018119

[Effects of excess vitamin B1 or vitamin B2 on growth and urinary excretion of water-soluble vitamins in weaning rats].

PubMed

Fukuwatari, Tsutomu; Kuzuya, Mako; Satoh, Shiori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake levels of vitamin B(1) and vitamin B(2) in humans, we investigated the effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet, corresponding to 900 mg/kg body weight/day.

Heightened avidity for trisodium pyrophosphate in mice lacking Tas1r3.

PubMed

Tordoff, Michael G; Aleman, Tiffany R; McCaughey, Stuart A

2015-01-01

Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6-56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8-56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Thiamin and Riboflavin in Human Milk: Effects of Lipid-Based Nutrient Supplementation and Stage of Lactation on Vitamer Secretion and Contributions to Total Vitamin Content

PubMed Central

Hampel, Daniela; Shahab-Ferdows, Setareh; Adair, Linda S.; Bentley, Margaret E.; Flax, Valerie L.; Jamieson, Denise J.; Ellington, Sascha R.; Tegha, Gerald; Chasela, Charles S.; Kamwendo, Debbie; Allen, Lindsay H.

2016-01-01

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer’s contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9–4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151μg/L (TMP), 13.3 versus 10.5μg/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8–19.6μg/L (LNS) versus 5.0–7.4μg/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92–94:6–8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The

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

PubMed Central

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

2015-01-01

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

Domain Organization in Candida glabrata THI6, a Bifunctional Enzyme Required for Thiamin Biosynthesis in Eukaryotes

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

Paul, Debamita; Chatterjee, Abhishek; Begley, Tadhg P.

2010-11-15

THI6 is a bifunctional enzyme found in the thiamin biosynthetic pathway in eukaryotes. The N-terminal domain of THI6 catalyzes the ligation of the thiamin thiazole and pyrimidine moieties to form thiamin phosphate, and the C-terminal domain catalyzes the phosphorylation of 4-methyl-5-hydroxyethylthiazole in a salvage pathway. In prokaryotes, thiamin phosphate synthase and 4-methyl-5-hydroxyethylthiazole kinase are separate gene products. Here we report the first crystal structure of a eukaryotic THI6 along with several complexes that characterize the active sites responsible for the two chemical reactions. THI6 from Candida glabrata is a homohexamer in which the six protomers form a cage-like structure. Eachmore » protomer is composed of two domains, which are structurally homologous to their monofunctional bacterial counterparts. Two loop regions not found in the bacterial enzymes provide interactions between the two domains. The structures of different protein-ligand complexes define the thiazole and ATP binding sites of the 4-methyl-5-hydroxyethylthiazole kinase domain and the thiazole phosphate and 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate binding sites of the thiamin phosphate synthase domain. Our structural studies reveal that the active sites of the two domains are 40 {angstrom} apart and are not connected by an obvious channel. Biochemical studies show 4-methyl-5-hydroxyethylthiazole phosphate is a substrate for THI6; however, adenosine diphospho-5{beta}-ethyl-4-methylthiazole-2-carboxylic acid, the product of THI4, is not a substrate for THI6. This suggests that an unidentified enzyme is necessary to produce the substrate for THI6 from the THI4 product.« less

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

LEFPS1, a Tomato Farnesyl Pyrophosphate Gene Highly Expressed during Early Fruit Development1

PubMed Central

Gaffe, Joel; Bru, Jean-Philippe; Causse, Mathilde; Vidal, Alain; Stamitti-Bert, Linda; Carde, Jean-Pierre; Gallusci, Philippe

2000-01-01

Farnesyl pyrophosphate synthase (FPS) catalyzes the synthesis of farnesyl pyrophosphate, a key intermediate in sterol and sesquiterpene biosynthesis. Using a polymerase chain reaction-based approach, we have characterized LeFPS1, a tomato (Lycoperscion esculentum cv Wva 106) fruit cDNA, which encodes a functional FPS. We demonstrate that tomato FPSs are encoded by a small multigenic family with genes located on chromosomes 10 and 12. Consistent with farnesyl pyrophosphate requirement in sterol biosynthesis, FPS genes are ubiquitously expressed in tomato plants. Using an LeFPS1 specific probe, we show that the corresponding gene can account for most of FPS mRNA in most plant organs, but not during young seedling development, indicating a differential regulation of FPS genes in tomato. FPS gene expression is also under strict developmental control: FPS mRNA was mainly abundant in young organs and decreased as organs matured with the exception of fruits that presented a biphasic accumulation pattern. In this latter case in situ hybridization studies have shown that FPS mRNA is similarly abundant in all tissues of young fruit. Taken together our results suggest that several FPS isoforms are involved in tomato farnesyl pyrophosphate metabolism and that FPS genes are mostly expressed in relation to cell division and enlargement. PMID:10938353

Disruption of Thiamine Uptake and Growth of Cells by Feline Leukemia Virus Subgroup A

PubMed Central

Mendoza, Ramon; Miller, A. Dusty

2013-01-01

Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection. PMID:23269813

Disruption of thiamine uptake and growth of cells by feline leukemia virus subgroup A.

PubMed

Mendoza, Ramon; Miller, A Dusty; Overbaugh, Julie

2013-03-01

Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection.

Thiamine Deficiency Induces Anorexia by Inhibiting Hypothalamic AMPK

PubMed Central

Liu, Mei; Alimov, Alexander; Wang, Haiping; Frank, Jacqueline A.; Katz, Wendy; Xu, Mei; Ke, Zun-Ji; Luo, Jia

2014-01-01

Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16 days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by 9 folds in TD group. The loss of body weight (17–24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic AMPK is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight. PMID:24607345

Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

MedlinePlus

... link) Biotin-Thiamine-Responsive Basal Ganglia Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- OR THIAMINE-RESPONSIVE TYPE) ...

Thiamine Deficiency Increases Ca2+ Current and CaV1.2 L-type Ca2+ Channel Levels in Cerebellum Granular Neurons.

PubMed

Moreira-Lobo, Daniel C; Cruz, Jader S; Silva, Flavia R; Ribeiro, Fabíola M; Kushmerick, Christopher; Oliveira, Fernando A

2017-04-01

Thiamine (vitamin B1) is co-factor for three pivotal enzymes for glycolytic metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Thiamine deficiency leads to neurodegeneration of several brain regions, especially the cerebellum. In addition, several neurodegenerative diseases are associated with impairments of glycolytic metabolism, including Alzheimer's disease. Therefore, understanding the link between dysfunction of the glycolytic pathway and neuronal death will be an important step to comprehend the mechanism and progression of neuronal degeneration as well as the development of new treatment for neurodegenerative states. Here, using an in vitro model to study the effects of thiamine deficiency on cerebellum granule neurons, we show an increase in Ca 2+ current density and Ca V 1.2 expression. These results indicate a link between alterations in glycolytic metabolism and changes to Ca 2+ dynamics, two factors that have been implicated in neurodegeneration.

Enhancement of Thiamine Biosynthesis in Oil Palm Seedlings by Colonization of Endophytic Fungus Hendersonia toruloidea

PubMed Central

Kamarudin, Amirah N.; Lai, Kok S.; Lamasudin, Dhilia U.; Idris, Abu S.; Balia Yusof, Zetty N.

2017-01-01

Thiamine, or vitamin B1 plays an indispensable role as a cofactor in crucial metabolic reactions including glycolysis, pentose phosphate pathway and the tricarboxylic acid cycle in all living organisms. Thiamine has been shown to play a role in plant adaptation toward biotic and abiotic stresses. The modulation of thiamine biosynthetic genes in oil palm seedlings was evaluated in response to root colonization by endophytic Hendersonia toruloidea. Seven-month-old oil palm seedlings were inoculated with H. toruloidea and microscopic analyses were performed to visualize the localization of endophytic H. toruloidea in oil palm roots. Transmission electron microscopy confirmed that H. toruloidea colonized cortical cells. The expression of thiamine biosynthetic genes and accumulation of total thiamine in oil palm seedlings were also evaluated. Quantitative real-time PCR was performed to measure transcript abundances of four key thiamine biosynthesis genes (THI4, THIC, TH1, and TPK) on days 1, 7, 15, and 30 in response to H. toruloidea colonization. The results showed an increase of up to 12-fold in the expression of all gene transcripts on day 1 post-inoculation. On days 7, 15, and 30 post-inoculation, the relative expression levels of these genes were shown to be downregulated. Thiamine accumulation was observed on day 7 post-colonization and subsequently decreased until day 30. This work provides the first evidence for the enhancement of thiamine biosynthesis by endophytic colonization in oil palm seedlings. PMID:29089959

Enhancement of Thiamine Biosynthesis in Oil Palm Seedlings by Colonization of Endophytic Fungus Hendersonia toruloidea.

PubMed

Kamarudin, Amirah N; Lai, Kok S; Lamasudin, Dhilia U; Idris, Abu S; Balia Yusof, Zetty N

2017-01-01

Thiamine, or vitamin B1 plays an indispensable role as a cofactor in crucial metabolic reactions including glycolysis, pentose phosphate pathway and the tricarboxylic acid cycle in all living organisms. Thiamine has been shown to play a role in plant adaptation toward biotic and abiotic stresses. The modulation of thiamine biosynthetic genes in oil palm seedlings was evaluated in response to root colonization by endophytic Hendersonia toruloidea . Seven-month-old oil palm seedlings were inoculated with H. toruloidea and microscopic analyses were performed to visualize the localization of endophytic H. toruloidea in oil palm roots. Transmission electron microscopy confirmed that H. toruloidea colonized cortical cells. The expression of thiamine biosynthetic genes and accumulation of total thiamine in oil palm seedlings were also evaluated. Quantitative real-time PCR was performed to measure transcript abundances of four key thiamine biosynthesis genes ( THI4 , THIC , TH1 , and TPK ) on days 1, 7, 15, and 30 in response to H. toruloidea colonization. The results showed an increase of up to 12-fold in the expression of all gene transcripts on day 1 post-inoculation. On days 7, 15, and 30 post-inoculation, the relative expression levels of these genes were shown to be downregulated. Thiamine accumulation was observed on day 7 post-colonization and subsequently decreased until day 30. This work provides the first evidence for the enhancement of thiamine biosynthesis by endophytic colonization in oil palm seedlings.

Illumina Sequencing Approach to Characterize Thiamine Metabolism Related Bacteria and the Impacts of Thiamine Supplementation on Ruminal Microbiota in Dairy Cows Fed High-Grain Diets.

PubMed

Pan, Xiaohua; Xue, Fuguang; Nan, Xuemei; Tang, Zhiwen; Wang, Kun; Beckers, Yves; Jiang, Linshu; Xiong, Benhai

2017-01-01

The requirements of thiamine in adult ruminants are mainly met by ruminal bacterial synthesis, and thiamine deficiencies will occur when dairy cows overfed with high grain diet. However, there is limited knowledge with regard to the ruminal thiamine synthesis bacteria, and whether thiamine deficiency is related to the altered bacterial community by high grain diet is still unclear. To explore thiamine synthesis bacteria and the response of ruminal microbiota to high grain feeding and thiamine supplementation, six rumen-cannulated Holstein cows were randomly assigned into a replicated 3 × 3 Latin square design trial. Three treatments were control diet (CON, 20% dietary starch, DM basis), high grain diet (HG, 33.2% dietary starch, DM basis) and high grain diet supplemented with 180 mg thiamine/kg DMI (HG+T). On day 21 of each period, rumen content samples were collected at 3 h postfeeding. Ruminal thiamine concentration was detected by high performance liquid chromatography. The microbiota composition was determined using Illumina MiSeq sequencing of 16S rRNA gene. Cows receiving thiamine supplementation had greater ruminal pH value, acetate and thiamine content in the rumen. Principal coordinate analysis and similarity analysis indicated that HG feeding and thiamine supplementation caused a strong shift in bacterial composition and structure in the rumen. At the genus level, compared with CON group, the relative abundances of 19 genera were significantly changed by HG feeding. Thiamine supplementation increased the abundance of cellulolytic bacteria including Bacteroides, Ruminococcus 1, Pyramidobacter, Succinivibrio , and Ruminobacter , and their increases enhanced the fiber degradation and ruminal acetate production in HG+T group. Christensenellaceae R7, Lachnospira, Succiniclasticum , and Ruminococcaceae NK4A214 exhibited a negative response to thiamine supplementation. Moreover, correlation analysis revealed that ruminal thiamine concentration was positively

Illumina Sequencing Approach to Characterize Thiamine Metabolism Related Bacteria and the Impacts of Thiamine Supplementation on Ruminal Microbiota in Dairy Cows Fed High-Grain Diets

PubMed Central

Pan, Xiaohua; Xue, Fuguang; Nan, Xuemei; Tang, Zhiwen; Wang, Kun; Beckers, Yves; Jiang, Linshu; Xiong, Benhai

2017-01-01

The requirements of thiamine in adult ruminants are mainly met by ruminal bacterial synthesis, and thiamine deficiencies will occur when dairy cows overfed with high grain diet. However, there is limited knowledge with regard to the ruminal thiamine synthesis bacteria, and whether thiamine deficiency is related to the altered bacterial community by high grain diet is still unclear. To explore thiamine synthesis bacteria and the response of ruminal microbiota to high grain feeding and thiamine supplementation, six rumen-cannulated Holstein cows were randomly assigned into a replicated 3 × 3 Latin square design trial. Three treatments were control diet (CON, 20% dietary starch, DM basis), high grain diet (HG, 33.2% dietary starch, DM basis) and high grain diet supplemented with 180 mg thiamine/kg DMI (HG+T). On day 21 of each period, rumen content samples were collected at 3 h postfeeding. Ruminal thiamine concentration was detected by high performance liquid chromatography. The microbiota composition was determined using Illumina MiSeq sequencing of 16S rRNA gene. Cows receiving thiamine supplementation had greater ruminal pH value, acetate and thiamine content in the rumen. Principal coordinate analysis and similarity analysis indicated that HG feeding and thiamine supplementation caused a strong shift in bacterial composition and structure in the rumen. At the genus level, compared with CON group, the relative abundances of 19 genera were significantly changed by HG feeding. Thiamine supplementation increased the abundance of cellulolytic bacteria including Bacteroides, Ruminococcus 1, Pyramidobacter, Succinivibrio, and Ruminobacter, and their increases enhanced the fiber degradation and ruminal acetate production in HG+T group. Christensenellaceae R7, Lachnospira, Succiniclasticum, and Ruminococcaceae NK4A214 exhibited a negative response to thiamine supplementation. Moreover, correlation analysis revealed that ruminal thiamine concentration was positively

Subcellular localization and compartmentation of thiamine derivatives in rat brain.

PubMed

Bettendorff, L; Wins, P; Lesourd, M

1994-05-26

The subcellular distribution of thiamine derivatives in rat brain was studied. Thiamine diphosphate content was highest in the mitochondrial and synaptosomal fractions, and lowest in microsomal, myelin and cytosolic fractions. Only 3-5% of total thiamine diphosphate was bound to transketolase, a cytosolic enzyme. Thiamine triphosphate was barely detectable in the microsomal and cytosolic fraction, but synaptosomes were slightly enriched in this compound compared to the crude homogenate. Both myelin and mitochondrial fractions contained significant amounts of thiamine triphosphate. In order to estimate the relative turnover rates of these compounds, the animals received an intraperitoneal injection of either [14C]thiamine or [14C]sulbutiamine (isobutyrylthiamine disulfide) 1 h before decapitation. The specific radioactivities of thiamine compounds found in the brain decreased in the order: thiamine > thiamine triphosphate > thiamine monophosphate > thiamine diphosphate. Incorporation of radioactivity into thiamine triphosphate was more marked with [14C]sulbutiamine than with [14C]thiamine. The highest specific radioactivity of thiamine diphosphate was found in the cytosolic fraction of the brain, though this pool represents less than 10% of total thiamine diphosphate. Cytosolic thiamine diphosphate had a twice higher specific radioactivity when [14C]sulbutiamine was used as precursor compared with thiamine though no significant differences were found in the other cellular compartments. Our results suggest the existence of two thiamine diphosphate pools: the bound cofactor pool is essentially mitochondrial and has a low turnover; a much smaller cytosolic pool (6-7% of total TDP) of high turnover is the likely precursor of thiamine triphosphate.

Population thiamine status and varying cancer rates between western, Asian and African countries.

PubMed

Boros, L G

2000-01-01

The role of food supplements in the form of vitamins has not been extensively investigated in relation to varying cancer rates between populations of different geographical regions. New data indicate that thiamine (vitamin B1), a common food supplement in Western food products, is directly involved in nucleic acid ribose synthesis of tumor cells in its biologically activated form through the non-oxidative transketolase catalyzed pentose cycle reaction. Whether thiamine plays a role in increased cancer rates in the Western World by enhancing tumor cell proliferation, while increased consumption of thiaminase rich food limiting thiamine availability protects against common malignancies in Asia and Africa has not been evaluated. In the Western World, thiamine is a popular vitamin supplement in the form of tablets and it is also added to basic food items such as milled flour, cereals, peanut butter, refreshment drinks and pastas. On the contrary, thiaminase, the natural thiamine-degrading enzyme, is abundantly present in raw and fermented fish, certain vegetables and roasted insects consumed primarily in Africa and Asia. Excess thiamine supplementation in common food products may contribute to the increased cancer rates of the Western World.

Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.

PubMed

Ortigoza-Escobar, Juan Darío; Molero-Luis, Marta; Arias, Angela; Oyarzabal, Alfonso; Darín, Niklas; Serrano, Mercedes; Garcia-Cazorla, Angels; Tondo, Mireia; Hernández, María; Garcia-Villoria, Judit; Casado, Mercedes; Gort, Laura; Mayr, Johannes A; Rodríguez-Pombo, Pilar; Ribes, Antonia; Artuch, Rafael; Pérez-Dueñas, Belén

2016-01-01

Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thiamine and fatty acid content of Lake Michigan Chinook salmon

USGS Publications Warehouse

Honeyfield, D.C.; Peters, A.K.; Jones, M.L.

2008-01-01

Nutritional status of Lake Michigan Chinook salmon (Oncorhynchus tshawytscha) is inadequately documented. An investigation was conducted to determine muscle and liver thiamine content and whole body fatty acid composition in small, medium and large Chinook salmon. Muscle and liver thiamine concentrations were highest in small salmon, and tended to decrease with increasing fish size. Muscle thiamine was higher in fall than spring in large salmon. The high percentage of Chinook salmon (24-32% in fall and 58-71% in spring) with muscle thiamine concentration below 500 pmol/g, which has been associated with loss of equilibrium and death in other Great Lake salmonines, suggest that Chinook appear to rely less on thiamine than other Great Lakes species for which such low concentrations would be associated with thiamine deficiency (Brown et al. 2005b). A positive correlation was observed between liver total thiamine and percent liver lipids (r = 0.53, P < 0.0001, n = 119). In medium and large salmon, liver lipids were observed to be low in fish with less than 4,000 pmol/g liver total thiamine. In individuals with greater than 4,000 pmol/g liver thiamine, liver lipid increased with thiamine concentration. Individual fatty acids declined between fall and spring. Essential omega-3 fatty acids appear to be conserved as lipid content declined. Arachidonic acid (C20:4n6), an essential omega-6 fatty acid was not different between fall and spring, although the sum of omega-6 (Sw6) fatty acids declined over winter. Elevated concentrations of saturated fatty acids (sum) were observed in whole body tissue lipid. In summary, thiamine, a dietary essential vitamin, and individual fatty acids were found to vary in Lake Michigan Chinook salmon by fish size and season of the year.

Perinatal consumption of thiamin-fortified fish sauce in rural Cambodia: a randomized controlled efficacy trial

USDA-ARS?s Scientific Manuscript database

Importance: Infantile beriberi, a potentially fatal disease caused by thiamin deficiency, remains a public health concern in Cambodia and regions where B-vitamin poor, polished white rice is a staple food. Low maternal thiamin intake reduces breast milk thiamin concentrations, placing breastfed infa...

The relationship between thiamine and two symbioses: Root nodule symbiosis and arbuscular mycorrhiza.

PubMed

Nagae, Miwa; Parniske, Martin; Kawaguchi, Masayoshi; Takeda, Naoya

2016-12-01

Lotus japonicus THIC is expressed in all organs, and the encoded protein catalyzes thiamine biosynthesis. Loss of function produces chlorosis, a typical thiamine-deficiency phenotype, and mortality. To investigate thiamine's role in symbiosis, we focused on THI1, a thiamine-biosynthesis gene expressed in roots, nodules, and seeds. The thi1 mutant had green leaves, but formed small nodules and immature seeds. These phenotypes were rescued by THI1 complementation and by exogenous thiamine. Thus, THI1 is required for nodule enlargement and seed maturation. On the other hand, colonization by arbuscular mycorrhiza (AM) fungus Rhizophagus irregularis was not affected in the thi1 mutant or by exogenous thiamine. However, spores of R. irregularis stored more thiamine than the source (host plants), despite lacking thiamine biosynthesis genes. Therefore, disturbance of the thiamine supply would affect progeny phenotypes such as spore formation and hyphal growth. Further investigation will be required to elucidate thiamine's effect on AM.

Beriberi (Thiamine Deficiency) and High Infant Mortality in Northern Laos

PubMed Central

Barennes, Hubert; Sengkhamyong, Khouanheuan; René, Jean Pascal; Phimmasane, Maniphet

2015-01-01

Background Infantile beriberi (thiamine deficiency) occurs mainly in infants breastfed by mothers with inadequate intake of thiamine, typically among vulnerable populations. We describe possible and probable cases of infantile thiamine deficiency in northern Laos. Methodology/Principal Findings Three surveys were conducted in Luang Namtha Province. First, we performed a retrospective survey of all infants with a diagnosis of thiamine deficiency admitted to the 5 hospitals in the province (2007–2009). Second, we prospectively recorded all infants with cardiac failure at Luang Namtha Hospital. Third, we further investigated all mothers with infants (1–6 months) living in 22 villages of the thiamine deficiency patients’ origin. We performed a cross-sectional survey of all mothers and infants using a pre-tested questionnaire, physical examination and squat test. Infant mortality was estimated by verbal autopsy. From March to June 2010, four suspected infants with thiamine deficiency were admitted to Luang Namtha Provincial hospital. All recovered after parenteral thiamine injection. Between 2007 and 2009, 54 infants with possible/probable thiamine deficiency were diagnosed with acute severe cardiac failure, 49 (90.2%) were cured after parenteral thiamine; three died (5.6%). In the 22 villages, of 468 live born infants, 50 (10.6%, 95% CI: 8.0–13.8) died during the first year. A peak of mortality (36 deaths) was reported between 1 and 3 months. Verbal autopsy suggested that 17 deaths (3.6%) were due to suspected infantile thiamine deficiency. Of 127 mothers, 60 (47.2%) reported edema and paresthesia as well as a positive squat test during pregnancy; 125 (98.4%) respected post-partum food avoidance and all ate polished rice. Of 127 infants, 2 (1.6%) had probable thiamine deficiency, and 8 (6.8%) possible thiamine deficiency. Conclusion Thiamine deficiency may be a major cause of infant mortality among ethnic groups in northern Laos. Mothers’ and children�

[Thiamine retention as a function of thermal processing conditions: canned salmon].

PubMed

Quitral, V; Romero, N; Avila, L; Marín, M E; Nuñez, H; Simpson, R

2006-03-01

The present work studied the effect of different treatments at high temperatures on the nutritional properties of thiamine retention and color measurement experimentally. Canned salmon (Salmo salar) was processed under different temperatures and time conditions (110 degrees C for 135 minutes; 114 degrees C for 89 minutes; 118 degrees C for 69 minutes and 121 degrees C for 62 minutes). Thiamine was determined by HPLC before and after the process. Color changes, due to processing conditions, were also measured utilizing a Hunter colorimeter. The canning was prepared in 300 x 407 cans and sterilized until Fo value reached 6 min. The nutritional value or index represented by the B1 vitamin or thiamine was affected by high temperature and time exposition. The lowest loss of thiamine of 19.2% was obtained in the canned salmon sterilized at 114 degrees C for 89 minutes. The color in canned salmon was different from the raw material, with a severe loss of red color and a greater clarity of the meat.

Thiamine transporter-2 deficiency: outcome and treatment monitoring.

PubMed

Ortigoza-Escobar, Juan Darío; Serrano, Mercedes; Molero, Marta; Oyarzabal, Alfonso; Rebollo, Mónica; Muchart, Jordi; Artuch, Rafael; Rodríguez-Pombo, Pilar; Pérez-Dueñas, Belén

2014-06-23

The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10-40 mg/kg/day) and biotin (1-2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.

The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells.

PubMed

Bettendorff, L

1994-05-26

Thiamine transport in cultured neuroblastoma cells is mediated by a high-affinity carrier (KM = 40 nM). In contrast, the uptake of the more hydrophobic sulbutiamine (isobutyrylthiamine disulfide) is unsaturable and its initial transport rate is 20-times faster than for thiamine. In the cytoplasm, sulbutiamine is rapidly hydrolyzed and reduced to free thiamine, the overall process resulting in a rapid and concentrative thiamine accumulation. Incorporation of radioactivity from [14C]thiamine or [14C]sulbutiamine into intracellular thiamine diphosphate is slow in both cases. Despite the fact that the diphosphate is probably the direct precursor for both thiamine monophosphate and triphosphate, the specific radioactivity increased much faster for the latter two compounds than for thiamine diphosphate. This suggests the existence of two pools of thiamine diphosphate, the larger one having a very slow turnover (about 17 h); a much smaller, rapidly turning over pool would be the precursor of thiamine mono- and triphosphate. The turnover time for thiamine triphosphate could be estimated to be 1-2 h. When preloading the cells with [14C]sulbutiamine was followed by a chase with the same concentration of the unlabeled compound, the specific radioactivities of thiamine and thiamine monophosphate decreased exponentially as expected, but labeling of the diphosphate continued to increase slowly. Specific radioactivity of thiamine triphosphate increased first, but after 30 min it began to slowly decrease. These results show for the first time the existence of distinct thiamine diphosphate pools in the same homogeneous cell population. They also suggest a complex compartmentation of thiamine metabolism.

Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone.

PubMed

Tabarki, Brahim; Alfadhel, Majid; AlShahwan, Saad; Hundallah, Khaled; AlShafi, Shatha; AlHashem, Amel

2015-09-01

To compare the combination of biotin plus thiamine to thiamine alone in treating patients with biotin-responsive basal ganglia disease in an open-label prospective, comparative study. twenty patients with genetically proven biotin-responsive basal ganglia disease were enrolled, and received for at least 30 months a combination of biotin plus thiamine or thiamine alone. The outcome measures included duration of the crisis, number of recurrence/admissions, the last neurological examination, the severity of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and the brain MRI findings during the crisis and after 30 months of follow-up. Ten children with a mean age of 6 years(1/2) were recruited in the biotin plus thiamine group (group 1) and ten children (6 females and 4 males) with a mean age of 6 years and 2 months were recruited in the thiamine group (group 2). After 2 years of follow-up treatment, 6 of 20 children achieved complete remission, 10 had minimal sequelae in the form of mild dystonia and dysarthria (improvement of the BFMDRS, mean: 80%), and 4 had severe neurologic sequelae. All these 4 patients had delayed diagnosis and management. Regarding outcome measures, both groups have a similar outcome regarding the number of recurrences, the neurologic sequelae (mean BFMDS score between the groups, p = 0.84), and the brain MRI findings. The only difference was the duration of the acute crisis: group 1 had faster recovery (2 days), versus 3 days in group 2 (p = 0.005). Our study suggests that over 30 months of treatment, the combination of biotin plus thiamine is not superior to thiamine alone in the treatment of biotin-responsive basal ganglia disease. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Determination of pyrophosphate and sulfate using polyhexamethylene guanidine hydrochloride-stabilized silver nanoparticles.

PubMed

Terenteva, E A; Apyari, V V; Dmitrienko, S G; Garshev, A V; Volkov, P A; Zolotov, Yu A

2018-04-01

Positively charged polyhexamethylene guanidine hydrochloride-stabilized silver nanoparticles (PHMG-AgNPs) were prepared and applied as a colorimetric probe for single-step determination of pyrophosphate and sulfate. The approach is based on the nanoparticles aggregation leading to change in their absorption spectra and color of the solution. Due to both electrostatic and steric stabilization these nanoparticles show decreased sensitivity relatively to many common anions, which allows for simple and rapid direct single-step determination of pyrophosphate and sulfate. Effects of different factors (time of interaction, pH, concentrations of anions and the nanoparticles) on aggregation of PHMG-AgNPs and analytical performance of the procedure were investigated. The method allows for the determination of pyrophosphate and sulfate in the range of 0.16-2μgmL -1 and 20-80μgmL -1 with RSD of 2-5%, respectively. The analysis can be performed using either spectrophotometry or naked-eye detection. Practical application of the method was shown by the example of pyrophosphate determination in baking powder sample. Copyright © 2017 Elsevier B.V. All rights reserved.

Thiamine transporter-2 deficiency: outcome and treatment monitoring

PubMed Central

2014-01-01

Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients. PMID:24957181

21 CFR 182.6787 - Sodium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6787 Sodium pyrophosphate. (a) Product. Sodium...

An exploratory assessment of thiamine status in western Alaska Chinook salmon (Oncorhynchus tshawytscha)

USGS Publications Warehouse

Honeyfield, Dale C.; Murphy, James M.; Howard, Katherine G.; Strasburger, Wesley W.; Matz, A.C.

2017-01-01

This study was conducted to investigate the thiamine status of Chinook salmon Oncorhynchus tshawytscha. Egg thiamine levels in Yukon and Kuskokwim River Chinook were examined in 2001 and 2012. Muscle and liver thiamine in Chinook, coho O. kisutch, chum O. keta, and pink O. gorbuscha salmon were measured in northern Bering Sea juveniles and the percentage of the diet containing thiaminase, an enzyme that destroys thiamine, was calculated. Only 23% of the eggs were thiamine replete (> 8.0 nmol·g-1) in 2012. Seventy-four percent of the eggs had thiamine concentrations (1.5–8.0 nmol·g-1) which can lead to mortality from secondary eff ects of thiamine defi ciency. Only 3% of the eggs had < 1.5 nmol·g-1 associated with overt fry mortality. In 2001 egg thiamine in upper Yukon Chinook was 11.7 nmol·g-1 which was higher than that measured in 2012 (6.2 nmol·g-1) and paralleled Chinook productivity. Total thiamine (nmol·g-1) in Bering Sea Chinook muscle (3.8) was similar to coho (4.15), but lower than in chum (8.9) and pink salmon (9.6). Thiaminase-containing prey in Chinook (63%) and coho (36%) stomachs were elevated compared to those of chum (3%) and pink (5%) salmon. These results provide evidence of egg thiamine being less than fully replete. Thiamine deficiency was not observed in juvenile muscle tissue, but differences were present among species reflecting the percentage of diet containing thiaminase. Additional studies are recommended.

Downbeat nystagmus caused by thiamine deficiency: an unusual presentation of CNS localization of large cell anaplastic CD 30-positive non-Hodgkin's lymphoma.

PubMed

Mulder, A H; Raemaekers, J M; Boerman, R H; Mattijssen, V

1999-02-01

A 24-year-old woman with a large cell anaplastic CD 30-positive T-cell non-Hodgkin's lymphoma (NHL) developed downbeat nystagmus, anisocoria, and oscillopsia. Prior to overt cerebral invasion by NHL, she had a thiamine deficiency with very low thiamine concentrations in the CSF, probably caused by protracted vomiting and increased vitamin B1 consumption by intrathecal tumor cells. We believe that her neurologic symptoms were caused -- at least partly -- by thiamine deficiency, as she reacted well to thiamine supplementation at the beginning of treatment.

Overexpression of a type-I isopentenyl pyrophosphate isomerase of Artemisia annua in the cytosol leads to high arteannuin B production and artemisinin increase.

PubMed

Ma, Dongming; Li, Gui; Alejos-Gonzalez, Fatima; Zhu, Yue; Xue, Zhen; Wang, Aimin; Zhang, Hui; Li, Xing; Ye, Hechun; Wang, Hong; Liu, Benye; Xie, De-Yu

2017-08-01

We recently characterized a gene-terpene network that is associated with artemisinin biosynthesis in self-pollinated (SP) Artemisia annua, an effective antimalarial plant. We hypothesize that an alteration of gene expression in the network may improve the production of artemisinin and its precursors. In this study, we cloned an isopentenyl pyrophosphate isomerase (IPPI) cDNA, AaIPPI1, from Artemisia annua (Aa). The full-length cDNA encodes a type-I IPPI containing a plastid transit peptide (PTP) at its amino terminus. After the removal of the PTP, the recombinant truncated AaIPPI1 isomerized isopentenyl pyrophosphate (IPP) to dimethyl allyl pyrophosphate (DMAPP) and vice versa. The steady-state equilibrium ratio of IPP/DMAPP in the enzymatic reactions was approximately 1:7. The truncated AaIPPI1 was overexpressed in the cytosol of the SP A. annua variety. The leaves of transgenic plants produced approximately 4% arteannuin B (g g -1 , dry weight, dw) and 0.17-0.25% artemisinin (g g -1 , dw), the levels of which were significantly higher than those in the leaves of wild-type plants. In addition, transgenic plants showed an increase in artemisinic acid production of more than 1% (g g -1 , dw). In contrast, isoprene formation was significantly reduced in transgenic plants. These results provide evidence that overexpression of AaIPPI1 in the cytosol can lead to metabolic alterations of terpenoid biosynthesis, and show that these transgenic plants have the potential to yield high production levels of arteannuin B as a new precursor source for artemisinin. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

PubMed Central

Pácal, Lukáš; Kuricová, Katarína; Kaňková, Kateřina

2014-01-01

Growing prevalence of diabetes (type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency (either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics (by review of the studies mapping the prevalence and the degree of thiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given. PMID:24936250

A Large Outbreak of Thiamine Deficiency Among Illegal Gold Miners in French Guiana

PubMed Central

Mosnier, Emilie; Niemetzky, Florence; Stroot, Juliette; de Santi, Vincent Pommier; Brousse, Paul; Guarmit, Basma; Blanchet, Denis; Ville, Muriel; Abboud, Philippe; Djossou, Felix; Nacher, Mathieu

2017-01-01

From September 2013 to July 2014, several gold miners working in the tropical forest consulted the Maripasoula Health Center in French Guiana for edema and findings consistent with right-sided cardiac failure. Of the 42 cases of beriberi that were diagnosed, one patient died. The laboratory and clinical investigation demonstrated vitamin B1 deficiency in most of the patients tested. Furthermore, 30 of 42 patients responded favorably to 500 mg of intravenous or intramuscular thiamine supplementation. In addition, dietary investigation showed insufficient thiamine intake in these patients. We concluded that patients had acquired beriberi because of diet restrictions, hard labor, and infectious diseases, notably malaria. In 2016, cases were still being reported. We recommend screening for compatible symptoms in gold miners, thiamine supplementation, and nutritional intervention. PMID:28500804

Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype.

PubMed

Liberman, M C; Tartaglini, E; Fleming, J C; Neufeld, E J

2006-09-01

Mutations in the gene coding for the high-affinity thiamine transporter Slc19a2 underlie the clinical syndrome known as thiamine-responsive megaloblastic anemia (TRMA) characterized by anemia, diabetes, and sensorineural hearing loss. To create a mouse model of this disease, a mutant line was created with targeted disruption of the gene. Cochlear function is normal in these mutants when maintained on a high-thiamine diet. When challenged with a low-thiamine diet, Slc19a2-null mice showed 40-60 dB threshold elevations by auditory brainstem response (ABR), but only 10-20 dB elevation by otoacoustic emission (OAE) measures. Wild-type mice retain normal hearing on either diet. Cochlear histological analysis showed a pattern uncommon for sensorineural hearing loss: selective loss of inner hair cells after 1-2 weeks on low thiamine and significantly greater inner than outer hair cell loss after longer low-thiamine challenges. Such a pattern is consistent with the observed discrepancy between ABR and OAE threshold shifts. The possible role of thiamine transport in other reported cases of selective inner hair cell loss is considered.

Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock.

PubMed

Costa, Nara Aline; Gut, Ana Lúcia; de Souza Dorna, Mariana; Pimentel, José Alexandre Coelho; Cozzolino, Silvia Maria Franciscato; Azevedo, Paula Schmidt; Fernandes, Ana Angélica Henrique; Zornoff, Leonardo Antonio Mamede; de Paiva, Sergio Alberto Rupp; Minicucci, Marcos Ferreira

2014-04-01

The purpose of the study is to determine the influence of serum thiamine, glutathione peroxidase (GPx) activity, and serum protein carbonyl concentrations in hospital mortality in patients with septic shock. This prospective study included all patients with septic shock on admission or during intensive care unit (ICU) stay, older than 18 years, admitted to 1 of the 3 ICUs of the Botucatu Medical School, from January to August 2012. Demographic information, clinical evaluation, and blood sample were taken within the first 72 hours of the patient's admission or within 72 hours after septic shock diagnosis for serum thiamine, GPx activity, and protein carbonyl determination. One hundred eight consecutive patients were evaluated. The mean age was 57.5 ± 16.0 years, 63% were male, 54.6% died in the ICU, and 71.3% had thiamine deficiency. Thiamine was not associated with oxidative stress. Neither vitamin B1 levels nor the GPx activity was associated with outcomes in these patients. However, protein carbonyl concentration was associated with increased mortality. In patients with septic shock, oxidative stress was associated with mortality. On the other hand, thiamine was not associated with oxidative stress or mortality in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Thiamine nutritional status and depressive symptoms are inversely associated among older Chinese adults.

PubMed

Zhang, Geng; Ding, Hanqing; Chen, Honglei; Ye, Xingwang; Li, Huaixing; Lin, Xu; Ke, Zunji

2013-01-01

Thiamine has been hypothesized to play an important role in mental health; however, few studies have investigated the association between thiamine nutritional status and depression in the general population. Concentrations of free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men and women aged 50-70 y. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score of ≥16. The median erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and 169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower concentrations of all 3 erythrocyte thiamine biomarkers were monotonically associated with a higher prevalence of depressive symptoms: the multivariable adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI = 1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P-trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP. In conclusion, poorer thiamine nutritional status and higher odds of depressive symptoms were associated among older Chinese adults. This finding should be further investigated in prospective or interventional studies.

Treatment with pyrophosphate inhibits uremic vascular calcification

PubMed Central

O’Neill, W. Charles; Lomashvili, Koba A.; Malluche, Hartmut H.; Faugere, Marie-Claude; Riser, Bruce L.

2011-01-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone. PMID:21124302

Treatment with pyrophosphate inhibits uremic vascular calcification.

PubMed

O'Neill, W Charles; Lomashvili, Koba A; Malluche, Hartmut H; Faugere, Marie-Claude; Riser, Bruce L

2011-03-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone.

Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

PubMed Central

Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

2016-01-01

In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

Arabidopsis TH2 Encodes the Orphan Enzyme Thiamin Monophosphate Phosphatase[OPEN

PubMed Central

Niehaus, Thomas D.; Hasnain, Ghulam; Gidda, Satinder K.; Nguyen, Thuy N.D.; Anderson, Erin M.; Brown, Greg; Yakunin, Alexander F.; de Crécy-Lagard, Valérie; Gregory, Jesse F.

2016-01-01

To synthesize the cofactor thiamin diphosphate (ThDP), plants must first hydrolyze thiamin monophosphate (ThMP) to thiamin, but dedicated enzymes for this hydrolysis step were unknown and widely doubted to exist. The classical thiamin-requiring th2-1 mutation in Arabidopsis thaliana was shown to reduce ThDP levels by half and to increase ThMP levels 5-fold, implying that the THIAMIN REQUIRING2 (TH2) gene product could be a dedicated ThMP phosphatase. Genomic and transcriptomic data indicated that TH2 corresponds to At5g32470, encoding a HAD (haloacid dehalogenase) family phosphatase fused to a TenA (thiamin salvage) family protein. Like the th2-1 mutant, an insertional mutant of At5g32470 accumulated ThMP, and the thiamin requirement of the th2-1 mutant was complemented by wild-type At5g32470. Complementation tests in Escherichia coli and enzyme assays with recombinant proteins confirmed that At5g32470 and its maize (Zea mays) orthologs GRMZM2G148896 and GRMZM2G078283 are ThMP-selective phosphatases whose activity resides in the HAD domain and that the At5g32470 TenA domain has the expected thiamin salvage activity. In vitro and in vivo experiments showed that alternative translation start sites direct the At5g32470 protein to the cytosol and potentially also to mitochondria. Our findings establish that plants have a dedicated ThMP phosphatase and indicate that modest (50%) ThDP depletion can produce severe deficiency symptoms. PMID:27677881

Thiamine Nutritional Status and Depressive Symptoms Are Inversely Associated among Older Chinese Adults123

PubMed Central

Zhang, Geng; Ding, Hanqing; Chen, Honglei; Ye, Xingwang; Li, Huaixing; Lin, Xu; Ke, Zunji

2013-01-01

Thiamine has been hypothesized to play an important role in mental health; however, few studies have investigated the association between thiamine nutritional status and depression in the general population. Concentrations of free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men and women aged 50–70 y. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score of ≥16. The median erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and 169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower concentrations of all 3 erythrocyte thiamine biomarkers were monotonically associated with a higher prevalence of depressive symptoms: the multivariable adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI = 1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P-trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP. In conclusion, poorer thiamine nutritional status and higher odds of depressive symptoms were associated among older Chinese adults. This finding should be further investigated in prospective or interventional studies. PMID:23173173

Prevalence of clinical thiamine deficiency in individuals with medically complicated obesity.

PubMed

Nath, Anand; Tran, Tung; Shope, Timothy R; Koch, Timothy R

2017-01-01

Thiamine is a vitamin whose deficient can result in multiorgan symptoms. We described an 18% prevalence of clinical thiamine deficiency after gastric bypass surgery. Our hypotheses are that individuals with medically complicated obesity frequently have clinical thiamine deficiency and that diabetes mellitus is a mechanism for development of clinical thiamine deficiency. This is a single institution, retrospective observational study of consecutive patients with a body mass index of at least 35 kg/m 2 who were evaluated in preoperative gastrointestinal bariatric clinic from 2013 to 2015. Each patient underwent a symptom survey. Clinical thiamine deficiency is defined by both (1) consistent clinical symptom and (2) either a low whole-blood thiamine concentration or significant improvement of or resolution of consistent clinical symptoms after receiving thiamine supplementation. After excluding 101 individuals with prior bariatric surgery or heavy alcohol consumption, 400 patients were included in the study. Sixty-six patients (16.5% of 400) fulfill a diagnosis of clinical thiamine deficiency, with 9 (14% of 66) having consistent gastrointestinal manifestations, 46 (70% of 66) having cardiac manifestations, 39 (59% of 66) having peripheral neurologic manifestations, and 3 (5% of 66) having neuropsychiatric manifestations. Diabetes mellitus is not a risk factor (P=.59). Higher body mass index is a significant risk for clinical thiamine deficiency (P=.007). Clinical thiamine deficiency is common in these individuals and a higher body mass index is an identified risk factor. Mechanisms explaining development of thiamine deficiency in obese individuals remain unclear. Copyright © 2016 Elsevier Inc. All rights reserved.

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives

PubMed Central

Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

2008-01-01

Background Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration. Results Benfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-β-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 μM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed. Conclusion Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

PubMed

Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

2008-06-12

Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration. Benfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-beta-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 muM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed. Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells

Thiamin deficiency in people with obesity.

PubMed

Kerns, Jennifer C; Arundel, Cherinne; Chawla, Lakhmir S

2015-03-01

Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included. © 2015 American Society for Nutrition.

Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate-Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilonproteobacteria

PubMed Central

Kennedy, Andrew J.; Bruce, Alexandra M.; Gineste, Catherine; Ballard, T. Eric; Olekhnovich, Igor N.; Macdonald, Timothy L.

2016-01-01

Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile. Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance. PMID:27090174

Genetics Home Reference: thiamine-responsive megaloblastic anemia syndrome

MedlinePlus

... Thiamine-responsive megaloblastic anemia syndrome Thiamine-responsive megaloblastic anemia syndrome Printable PDF Open All Close All Enable ... the expand/collapse boxes. Description Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing ...

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP.

PubMed

Bickford, Justin S; Nick, Harry S

2013-12-01

Isoprenoid lipid carriers are essential in protein glycosylation and bacterial cell envelope biosynthesis. The enzymes involved in their metabolism (synthases, kinases and phosphatases) are therefore critical to cell viability. In this review, we focus on two broad groups of isoprenoid pyrophosphate phosphatases. One group, containing phosphatidic acid phosphatase motifs, includes the eukaryotic dolichyl pyrophosphate phosphatases and proposed recycling bacterial undecaprenol pyrophosphate phosphatases, PgpB, YbjB and YeiU/LpxT. The second group comprises the bacterial undecaprenol pyrophosphate phosphatase, BacA/UppP, responsible for initial formation of undecaprenyl phosphate, which we predict contains a tyrosine phosphate phosphatase motif resembling that of the tumour suppressor, phosphatase and tensin homologue (PTEN). Based on protein sequence alignments across species and 2D structure predictions, we propose catalytic and lipid recognition motifs unique to BacA/UppP enzymes. The verification of our proposed active-site residues would provide new strategies for the development of substrate-specific inhibitors which mimic both the lipid and pyrophosphate moieties, leading to the development of novel antimicrobial agents.

Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Puts, Johan; de Groot, Monique; Haex, Martin; Jakobs, Bernadette

2015-01-01

Background Vitamin B1 (thiamine-diphosphate) and B6 (pyridoxal-5’phosphate) are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC) based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid Chromatography Tandem Mass spectrometry (UHPLC-MS/MS) assay with internal standards for simultaneous measurement of underivatized thiamine-diphosphate and pyridoxal-5’phosphate without use of ion pairing reagent. Methods Whole blood, deproteinized with perchloric acid, containing deuterium labelled internal standards thiamine-diphosphate(thiazole-methyl-D3) and pyridoxal-5’phosphate(methyl-D3), was analyzed by UHPLC-MS/MS. The method was validated for imprecision, linearity, recovery and limit of quantification. Alternate (quantitative) method comparisons of the new versus currently used routine HPLC methods were established with Deming regression. Results Thiamine-diphosphate and pyridoxal-5’phosphate were measured within 2.5 minutes instrumental run time. Limits of detection were 2.8 nmol/L and 7.8 nmol/L for thiamine-diphosphate and pyridoxal-5’phosphate respectively. Limit of quantification was 9.4 nmol/L for thiamine-diphosphate and 25.9 nmol/L for pyridoxal-5’phosphate. The total imprecision ranged from 3.5–7.7% for thiamine-diphosphate (44–157 nmol/L) and 6.0–10.4% for pyridoxal-5’phosphate (30–130 nmol/L). Extraction recoveries were 101–102% ± 2.5% (thiamine-diphosphate) and 98–100% ± 5% (pyridoxal-5’phosphate). Deming regression yielded slopes of 0.926 and 0.990 in patient samples (n = 282) and national proficiency testing samples (n = 12) respectively, intercepts of +3.5 and +3 for thiamine-diphosphate (n = 282 and n = 12) and slopes of

A novel thiamine-derived pigment, pyrizepine, formed by the Maillard reaction.

PubMed

Igoshi, Asuka; Noda, Kyoko; Murata, Masatsune

2018-04-26

To find a Maillard pigment derived from thiamine, a solution containing glucose and thiamine was heated and analyzed with high-performance liquid chromatography equipped with diode-array detection. As a result, a unique peak showing an absorption maximum at 380 nm was detected. This peak was then isolated from a reaction solution containing glucose, lysine and thiamine, and was identified as 1-(2-methyl-6,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7-yl)ethan-1-one using instrumental analyses. This compound, named pyrizepine, was a novel yellow pigment having a fused ring consisting of pyrimidine and diazepine. Pyrizepine was a major low-molecular-weight pigment in the reaction solution. The structure suggests that pyrizepine is formed by condensation reaction between a degradation product of thiamine and a tetrosone derivative formed from glucose by the Maillard reaction.

Crystallization and preliminary X-ray diffraction study of phosphoribosyl pyrophosphate synthetase from E. Coli

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

Timofeev, V. I., E-mail: inna@ns.crys.ras.ru; Abramchik, Yu. A., E-mail: tostars@mail.ru; Zhukhlistova, N. E., E-mail: ugama@yandex.ru

2015-09-15

Enzymes of the phosphoribosyl pyrophosphate synthetase family (PRPPS, EC 2.7.6.1) catalyze the formation of 5-phosphoribosyl pyrophosphate (5-PRPP) from adenosine triphosphate and ribose 5-phosphate. 5-Phosphoribosyl pyrophosphate is an important intermediate in the synthesis of purine, pyrimidine, and pyridine nucleotides, as well as of the amino acids histidine and tryptophan. The crystallization conditions for E. coli PRPPS were found by the vapor-diffusion technique and were optimized to apply the capillary counter-diffusion technique. The X-ray diffraction data set was collected from the crystals grown by the counter-diffusion technique using a synchrotron radiation source to 3.1-Å resolution. The crystals of PRPPS belong to sp.more » gr. P6{sub 3}22 and have the following unit-cell parameters: a = b = 104.44 Å, c = 124.98 Å, α = β = 90°, γ = 120°. The collected X-ray diffraction data set is suitable for the solution of the three-dimensional structure of PRPPS at 3.1-Å resolution.« less

Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stress-induced behaviours in mice.

PubMed

Markova, Nataliia; Bazhenova, Nataliia; Anthony, Daniel C; Vignisse, Julie; Svistunov, Andrey; Lesch, Klaus-Peter; Bettendorff, Lucien; Strekalova, Tatyana

2017-04-03

Thiamine (vitamin B1) deficiency in the brain has been implicated in the development of dementia and symptoms of depression. Indirect evidence suggests that thiamine may contribute to these pathologies by controlling the activities of glycogen synthase kinase (GSK)-3β. While decreased GSK-3β activity appears to impair memory, increased GSK-3β activity is associated with the distressed/depressed state. However, hitherto direct evidence for the effects of thiamine on GSK-3β function has not been reported. Here, we administered thiamine or, the more bioavailable precursor, benfotiamine at 200mg/kg/day for 2weeks to C57BL/6J mice, to determine whether treatment might affect behaviours that are known to be sensitive to GSK-3β activity and whether such administration impacts on GSK-3β expression within the brain. The mice were tested in models of contextual conditioning and extinction, a 5-day rat exposure stress test, and a modified swim test with repeated testing. The tricyclic antidepressant imipramine (7.5mg/kg/day), was administered as a positive control for the effects of thiamine or benfotiamine. As for imipramine, both compounds inhibited the upregulation of GSK-3β induced by predator stress or repeated swimming, and reduced floating scores and the predator stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine and benfotiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Our data indicate that thiamine and benfotiamine have antidepressant/anti-stress effects in naïve animals that are associated with reduced GSK-3β expression and conditioning of adverse memories. Thus thiamine and benfotiamine may modulate GSK-3β functions in a manner that is dependent on whether the contextual conditioning is adaptive or maladaptive. Copyright © 2016 Elsevier Inc. All rights reserved.

Thiamine preserves mitochondrial function in a rat model of traumatic brain injury, preventing inactivation of the 2-oxoglutarate dehydrogenase complex.

PubMed

Mkrtchyan, Garik V; Üçal, Muammer; Müllebner, Andrea; Dumitrescu, Sergiu; Kames, Martina; Moldzio, Rudolf; Molcanyi, Marek; Schaefer, Samuel; Weidinger, Adelheid; Schaefer, Ute; Hescheler, Juergen; Duvigneau, Johanna Catharina; Redl, Heinz; Bunik, Victoria I; Kozlov, Andrey V

2018-05-16

Based on the fact that traumatic brain injury is associated with mitochondrial dysfunction we aimed at localization of mitochondrial defect and attempted to correct it by thiamine. Interventional controlled experimental animal study was used. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion traumatic brain injury. Thiamine was administered 1 h prior to trauma; cortex was extracted for analysis 4 h and 3 d after trauma. Increased expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor receptor 1 (TNF-R1) by 4 h was accompanied by a decrease in mitochondrial respiration with glutamate but neither with pyruvate nor succinate. Assays of TCA cycle flux-limiting 2-oxoglutarate dehydrogenase complex (OGDHC) and functionally linked enzymes (glutamate dehydrogenase, glutamine synthetase, pyruvate dehydrogenase, malate dehydrogenase and malic enzyme) indicated that only OGDHC activity was decreased. Application of the OGDHC coenzyme precursor thiamine rescued the activity of OGDHC and restored mitochondrial respiration. These effects were not mediated by changes in the expression of the OGDHC sub-units (E1k and E3), suggesting post-translational mechanism of thiamine effects. By the third day after TBI, thiamine treatment also decreased expression of TNF-R1. Specific markers of unfolded protein response did not change in response to thiamine. Our data point to OGDHC as a major site of damage in mitochondria upon traumatic brain injury, which is associated with neuroinflammation and can be corrected by thiamine. Further studies are required to evaluate the pathological impact of these findings in clinical settings. Copyright © 2018. Published by Elsevier B.V.

Effect of blood thiamine concentrations on mortality: Influence of nutritional status.

PubMed

Leite, Heitor Pons; de Lima, Lúcio Flávio Peixoto; Taddei, José Augusto de A C; Paes, Ângela Tavares

2018-04-01

To test the hypothesis that low blood thiamine concentrations in malnourished critically ill children are associated with higher risk of 30-d mortality. Prospective cohort study in 202 consecutively admitted children who had whole blood thiamine concentrations assessed on admission and on days 5 and 10 of intensive care unit (ICU) stay. The primary outcome variable was 30-d mortality. Mean blood thiamine concentrations within the first 10 d of ICU stay, age, sex, malnutrition, C-reactive protein concentration, Pediatric Index of Mortality 2 score, and severe sepsis/septic shock were the main potential exposure variables for outcome. Thiamine deficiency was detected in 61 patients within the first 10 d of ICU stay, 57 cases being diagnosed on admission and 4 new cases on the 5th d. C-reactive protein concentration during ICU stay was independently associated with decreased blood thiamine concentrations (P = 0.003). There was a significant statistical interaction between mean blood thiamine concentrations and malnutrition on the risk of 30-d mortality (P = 0.002). In an adjusted analysis, mean blood thiamine concentrations were associated with a decrease in the mortality risk in malnourished patients (odds ratio = 0.85; 95% confidence interval [CI]: 0.73-0.98; P = 0.029), whereas no effect was noted for well-nourished patients (odds ratio: 1.03; 95% CI: 0.94-1.13; P = 0.46). Blood thiamine concentration probably has a protective effect on the risk of 30-d mortality in malnourished patients but not in those who were well nourished. Copyright © 2017 Elsevier Inc. All rights reserved.

Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

PubMed

Vignisse, Julie; Sambon, Margaux; Gorlova, Anna; Pavlov, Dmitrii; Caron, Nicolas; Malgrange, Brigitte; Shevtsova, Elena; Svistunov, Andrey; Anthony, Daniel C; Markova, Natalyia; Bazhenova, Natalyia; Coumans, Bernard; Lakaye, Bernard; Wins, Pierre; Strekalova, Tatyana; Bettendorff, Lucien

2017-07-01

Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent

Interaction of 2,4-Diaminopyrimidine-Containing Drugs Including Fedratinib and Trimethoprim with Thiamine Transporters.

PubMed

Giacomini, Marilyn M; Hao, Jia; Liang, Xiaomin; Chandrasekhar, Jayaraman; Twelves, Jolyn; Whitney, J Andrew; Lepist, Eve-Irene; Ray, Adrian S

2017-01-01

Inhibition of thiamine transporters has been proposed as a putative mechanism for the observation of Wernicke's encephalopathy and subsequent termination of clinical development of fedratinib, a Janus kinase inhibitor (JAKi). This study aimed to determine the potential for other JAKi to inhibit thiamine transport using human epithelial colorectal adenocarcinoma (Caco-2) and thiamine transporter (THTR) overexpressing cells and to better elucidate the structural basis for interacting with THTR. Only JAKi containing a 2,4-diaminopyrimidine were observed to inhibit thiamine transporters. Fedratinib inhibited thiamine uptake into Caco-2 cells (IC 50 = 0.940 µM) and THTR-2 (IC 50 = 1.36 µM) and, to a lesser extent, THTR-1 (IC 50 = 7.10 µM) overexpressing cells. Two other JAKi containing this moiety, AZD1480 and cerdulatinib, were weaker inhibitors of the thiamine transporters. Other JAKi-including monoaminopyrimidines, such as momelotinib, and nonaminopyrimidines, such as filgotinib-did not have any inhibitory effects on thiamine transport. A pharmacophore model derived from the minimized structure of thiamine suggests that 2,4-diaminopyrimidine-containing compounds can adopt a conformation matching several key features of thiamine. Further studies with drugs containing a 2,4-diaminopyrimidine resulted in the discovery that the antibiotic trimethoprim also potently inhibits thiamine uptake mediated by THTR-1 (IC 50 = 6.84 µM) and THTR-2 (IC 50 = 5.56 µM). Fedratinib and trimethoprim were also found to be substrates for THTR, a finding with important implications for their disposition in the body. In summary, our results show that not all JAKi have the potential to inhibit thiamine transport and further establish the interaction of these transporters with xenobiotics. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Screening of a thiamine-auxotrophic yeast for alpha-ketoglutaric acid overproduction.

PubMed

Zhou, Jingwen; Zhou, Haiyan; Du, Guocheng; Liu, Liming; Chen, Jian

2010-09-01

To obtain a thiamine-auxotrophic yeast strain that overproduces alpha-ketoglutaric acid (alpha-KG) from glycerol and to investigate nutrient effects on alpha-KG production. Yeast strain WSH-Z06, a thiamine auxotroph that gave high yields of alpha-KG from glycerol, was obtained by screening for ampicillin/kanamycin resistance and thiamine auxotrophy. The strain was identified as Yarrowia lipolytica based on physiological, chemical, and phylogenetic analysis. The ability of the strain to convert glycerol to alpha-KG was analysed by investigating the effects of nutritional factors, including thiamine, riboflavin, nitrogen sources, and calcium ion. Thiamine and calcium ion concentration had the greatest effect on alpha-KG accumulation. Under optimal conditions, a yield of 39.2 g l(-1)alpha-KG was obtained from 100 g l(-1) glycerol, with 16.84 g l(-1) pyruvate as a by-product. The current work provides a method for screening for an alpha-KG overproducer. Nutrients have a significant impact on alpha-KG production in the yeast strain presented here. The alpha-KG-overproducing yeast strain Y. lipolytica WSH-Z06 is a promising parent strain for further metabolic engineering to lower by-product accumulation and accelerate glycerol utilization.

Dietary intake of the water-soluble vitamins B1, B2, B6, B12 and C in 10 countries in the European Prospective Investigation into Cancer and Nutrition.

PubMed

Olsen, A; Halkjaer, J; van Gils, C H; Buijsse, B; Verhagen, H; Jenab, M; Boutron-Ruault, M C; Ericson, U; Ocké, M C; Peeters, P H M; Touvier, M; Niravong, M; Waaseth, M; Skeie, G; Khaw, K T; Travis, R; Ferrari, P; Sanchez, M J; Agudo, A; Overvad, K; Linseisen, J; Weikert, C; Sacerdote, C; Evangelista, A; Zylis, D; Tsiotas, K; Manjer, J; van Guelpen, B; Riboli, E; Slimani, N; Bingham, S

2009-11-01

To describe the intake of vitamins thiamine (B1), riboflavin (B2), B6 (pyridoxine), B12 (cobalamine) and C (ascorbic acid) and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Between 1995 and 2000, 36 034 persons aged between 35 and 74 years were administered a standardized 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes of the four B vitamins and vitamin C were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age and weighted by season and day of recall. Intake of B vitamins did not vary considerably between centres, except in the UK health-conscious cohort, in which substantially higher intakes of thiamine and lower intakes of vitamin B12 were reported compared with other centres. Overall, meat was the most important contributor to the B vitamins in all centres except in the UK health-conscious group. Vitamin C showed a clear geographical gradient, with higher intakes in the southern centres as compared with the northern ones; this was more pronounced in men than in women. Vegetables and fruits were major contributors to vitamin C in all centres, but juices and potatoes were also important sources in the northern centres. This study showed no major differences across centres in the mean intakes of B vitamins (thiamine, riboflavin, B6, B12), whereas a tendency towards a north-south gradient was observed for vitamin C.

Investigating the pharmacodynamic and magnetic properties of pyrophosphate-bridged coordination complexes

NASA Astrophysics Data System (ADS)

Ikotun, Oluwatayo (Tayo) F.

The multidentate nature of pyrophosphate makes it an attractive ligand for complexation of metal cations. The participation of pyrophosphate in a variety of biological pathways and its metal catalyzed hydrolysis has driven our investigation into its coordination chemistry. We have successfully synthesized a library of binuclear pyrophosphate bridge coordination complexes. The problem of pyrophosphate hydrolysis to phosphate in the presence of divalent metal ions was overcome by incorporating capping ligands such as 1,10-phenanthroline and 2,2'-bipyridine prior to the addition of the pyrophosphate. The magnetic properties of these complexes was investigated and magneto-structural analysis was conducted. The biological abundance of pyrophosphate and the success of metal based drugs such as cisplatin, prompted our investigation of the cytotoxic properties of M(II) pyrophosphate dimeric complexes (where M(II) is CoII, CuII, and NiII) in adriamycin resistant human ovarian cancer cells. Thess compounds were found to exhibit toxicity in the nanomolar to picomolar range. We conducted in vitro stability studies and the mechanism of cytoxicity was elucidated by performing DNA mobility and binding assays, enzyme inhibition assays, and in vitro oxidative stress studies.

Simultaneous in situ derivatization and ultrasound-assisted dispersive magnetic solid phase extraction for thiamine determination by spectrofluorimetry.

PubMed

Tarigh, Ghazale Daneshvar; Shemirani, Farzaneh

2014-06-01

A simple and rapid method for the simultaneous in situ derivatizaion, preconcentration and extraction of thiamine (vitamin B1) as a model analyte was developed by a novel quantitative method, namely ultrasound-assisted dispersive magnetic solid phase extraction spectrofluorimetry (USA-DMSPE-FL) from different real samples. This method consists of sample preparation, in situ derivatization, exhaustive extraction and clean up by a single process. High extraction efficiency and in situ derivatization in a short period of time is the main advantages of this procedure. For this purpose, the reusable magnetic multi-wall carbon nanotube (MMWCNT) nanocomposite was used as an adsorbent for preconcentration and determination of thiamine. Thiamine was, simultaneously, in situ derivatized as thiochrome by potassium hexacyanoferrate (III) and adsorbed on MMWCNT in an ultrasonic water bath. The MMWCNTs were then collected using an external magnetic field. Subsequently, the extracted thiochrome was washed from the surface of the adsorbent and determined by spectrofluorimetry. The developed method, which has been analytically characterized under its optimal operating conditions, allows the detection of the analyte in the samples with method detection limits of 0.37 µg L(-1). The repeatability of the method, expressed as the relative standard deviation (RSD, n=6), varies between 2.0% and 4.8% in different real samples, while the enhancement factor is 197. The proposed procedure has been applied for the determination of thiamine in biological (serum and urine), pharmaceutical (multivitamin tablet and B complex syrup) and foodstuff samples (cereal, wheat flour, banana and honey) with the good recoveries in the range from 90% to 105%. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of gamma irradiation on the thiamine, riboflavin and vitamin B 6 content in two varieties of Brazilian beans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H. A. L. C. H.; Mancini-Filho, J. J.; Delincée, H. H.; Bognár, A. A.

2000-03-01

The effect of 60Co gamma rays on the content of several B-vitamins in two varieties of Brazilian beans has been studied. Carioca ( Phaseolus vulgaris L. var. Carioca) and Macaçar beans ( Vigna unguiculata L. Walp, var. Macaçar) were irradiated at doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy, and subsequently stored at ambient temperature for 6 months. The content of vitamin B 1, B 2 and B 6 was analysed by HPLC. In addition, the optimum cooking time was established for each dose and bean variety. A taste panel evaluated sensory properties. Only slight changes were measured for thiamine and riboflavin, whereas a dose-dependent decrease was noted for pyridoxine, which, however, was significant only at the highest doses of 5 and 10 kGy. Cooking time was considerably reduced with increasing radiation dose, but accompanied by a loss of the sensory quality. However, at the disinfestation dose up to 1 kGy, acceptable ratings were obtained for the sensory evaluation. In conclusion, for insect disinfestation of Brazilian beans radiation processing is a promising technology.

Presumed primary thiamine deficiency in a young African lion (Panthera leo).

PubMed

DiGesualdo, Cynthia L; Hoover, John P; Lorenz, Michael D

2005-09-01

A 1-yr-old intact male African lion (Panthera leo) fed only beef muscle meat was evaluated for episodes of hypermetric ataxia, generalized weakness and tonic-clonic front limb movements. A hemogram, biochemical profile, blood lead, electrocardiogram, survey radiographs, and brain computed tomography were normal. Cerebral spinal fluid analyses suggested mild inflammation. Acetylcholine receptor antibody and serologic tests for all infectious agents tested were negative. Clinical signs resolved completely 9 days after instituting oral thiamine (3 mg/kg/day) and a completely nutritional diet. This lion's pretreatment thiamine blood value (11 nmol/L) was markedly lower than that of a healthy lion (191 nmol/L) and a proposed reference range for adult African lions (160-350 nmol/L). The lion remained clinically normal 2 yr later when his blood thiamine value was 340 nmol/L. African lions can develop clinical primary thiamine deficiency and may respond favorably when thiamine treatment and adequate diet are instituted prior to irreversible neuronal necrosis.

PREPARATION OF ALKYL PYROPHOSPHATE EXTRACTANTS

DOEpatents

Levine, C.A.; Skiens, W.E.; Moore, G.R.

1960-08-01

A process for providing superior solvent extractants for metal recovery processes is given wherein the extractant comprises an alkyl pyrophosphoric acid ester dissolved in an organic solvent diluent. Finely divided solid P/sub 2/O/ sub 5/ is slurried in an organic solvent-diluent selected from organic solvents such as kerosene, benzene, chlorobenzene, toluene, etc. An alcohol selected from the higher alcohols having 4 to 17 carbon atoms. e.g.. hexanol-1. heptanol-3, octanol-1. 2.6-dimethyl-heptanol-4, and decanol-1, is rapidly added to the P/sub 2/O/sub 5/ slurry in the amount of about 2 moles of alcohol to 1 mole of P/sub 2/ O/sub 5/. The temperature is maintained below about 110 deg C during the course of the P/sub 2/O/sub 5/-alcohol reaction. An alkyl pyrophosphate extractant compound is formed as a consequence of the reaction process. The alkyl pyrophosphate solvent-diluent extractant phase is useful in solvent extraction metal recovery processes.

Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate-Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilonproteobacteria.

PubMed

Kennedy, Andrew J; Bruce, Alexandra M; Gineste, Catherine; Ballard, T Eric; Olekhnovich, Igor N; Macdonald, Timothy L; Hoffman, Paul S

2016-07-01

Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4'-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Perinatal thiamine deficiency-induced spontaneous abortion and pup-killing responses in rat dams.

PubMed

Bâ, Abdoulaye

2013-03-01

The current study attempts to determine whether thiamine (B1 vitamin) deficiency and chronic alcohol-related thiamine-deficient (TD) status, disturb maternal behavior towards pups. During gestation and lactation, Wistar rat dams were exposed to the following treatments: (i) prenatal TD dams; (ii) perinatal TD dams; (iii) postnatal TD dams; (iv) 12% alcohol/water drinking mothers; (v) ad libitum control dams. Pair-feeding treatments controlled malnutrition related to thiamine deficiency; (vi) prenatal pair-fed (PF) dams; (vii) perinatal PF dams; (viii) postnatal PF dams and included also the control of alcohol consummation: (ix) PF saccharose dams. Dams were observed for gestation outcome and for apparent disorders of the maternal behavior related to the pups at parturition. From the nine experimental groups studied, only pre- and perinatal TD dams exhibited spontaneous abortion (33.36 and 41.66%, respectively) followed by pups-killing responses where, respectively, 4 dams/7 (57.14%) and 5 dams/7 (71.43%) showed disruption of maternal behavior and appearance of cannibalism towards pups which all were killed within 48 hours after parturition. Spontaneous abortion and pup-killing responses were not observed in the dams of any other experimental group, suggesting that perinatal disturbances of hormonal factors underlay these maternal disorders. Previous studies reported that thiamine deficiency-induced degeneration of dopamine neurons may be related to mouse-killing aggression in rats. The present study suggests that perinatal thiamine deficiency-induced alteration of dopaminergic neurons in maternal brain could be a trigger factor of pup-killing responses. Central dopamine and oxytocin have been strongly associated with both the onset and maintenance of maternal behavior and the regulation of maternal aggressiveness as well. Our studies suggest that estrogen control oxytocin levels in brain structures of pregnancy-terminated rats via dopamine transmission. Thiamine

A rapid solid-phase extraction fluorometric method for thiamine and riboflavin in salmonid eggs

USGS Publications Warehouse

Zajicek, James L.; Tillitt, Donald E.; Brown, Scott B.; Brown, Lisa R.; Honeyfield, Dale C.; Fitzsimons, John D.

2005-01-01

A new method has been developed and successfully applied to the selective measurement of thiamine (nonphosphorylated), total thiamine (sum of thiamine, thiamine monophosphate [TMP], thiamine diphosphate [TDP], and thiamine triphosphate [TTP]), and potentially interfering riboflavin in acidic (2% trichloroacetic acid) extracts of selected salmonid and walleye egg samples. Acidic extracts of eggs were applied directly to end-capped C18, reversed-phase solid-phase extraction (SPE) columns and separated into three fractions by elution with mixtures of PO4 buffer (pH 2), methanol (10%), and acetonitrile (20%). All thiamine compounds recovered in the first two fractions were oxidized to their corresponding thiochromes with alkaline potassium hexacyanoferrate, and we measured the thiochrome fluorescence (excitation at 360 nm, emission at 460 nm) in a 96-well microplate reader. Riboflavin, recovered in third fraction (eluted with pH 2, 20% acetonitrile), was analyzed directly by measuring the fluorescence of this fraction (excitation at 450 nm, emission at 530 nm). Significant portions of the phosphate esters of thiamine (TMP, TDP, and presumably TTP), when present at low concentrations (< 10 nmol of total -thiamine per gram of egg), were not retained by the 100-mg SPE column, and were collected directly during sample loading and in a subsequent phosphoric acid rinse as fraction 1. Free thiamine (nonphosphorylated) and remaining portions of the TDP and TMP were then eluted in the second fraction with 10% methanol/PO4 buffer, whereas the un-ionized, relatively nonpolar riboflavin was eluted in the third fraction with 20% acetonitrile. This new method uses a traditional sample homogenization of egg tissue to extract thiamine compounds into 2% trichlororacetic acid solution; an inexpensive, commercially available SPE column; small amounts of sample (0.5-1 g); microliter volumes of solvents per sample; a traditional, relatively nonhazardous, oxidation of thiamine compounds to

The effect of subclinical infantile thiamine deficiency on motor function in preschool children.

PubMed

Harel, Yael; Zuk, Luba; Guindy, Michal; Nakar, Orly; Lotan, Dafna; Fattal-Valevski, Aviva

2017-10-01

We investigated the long-term implications of infantile thiamine (vitamin B1) deficiency on motor function in preschoolers who had been fed during the first 2 years of life with a faulty milk substitute. In this retrospective cohort study, 39 children aged 5-6 years who had been exposed to a thiamine-deficient formula during infancy were compared with 30 age-matched healthy children with unremarkable infant nutritional history. The motor function of the participants was evaluated with The Movement Assessment Battery for Children (M-ABC) and the Zuk Assessment. Both evaluation tools revealed statistically significant differences between the exposed and unexposed groups for gross and fine motor development (p < .001, ball skills p = .01) and grapho-motor development (p = .004). The differences were especially noteworthy on M-ABC testing for balance control functioning (p < .001, OR 5.4; 95% CI 3.4-7.4) and fine motor skills (p < .001, OR 3.2; 95% CI 1.8-4.6). In the exposed group, both assessments concurred on the high rate of children exhibiting motor function difficulties in comparison to unexposed group (M-ABC: 56% vs. 10%, Zuk Assessment: 59% vs. 3%, p < .001). Thiamine deficiency in infancy has long-term implications on gross and fine motor function and balance skills in childhood, thiamine having a crucial role in normal motor development. The study emphasizes the importance of proper infant feeding and regulatory control of breast milk substitutes. © 2017 John Wiley & Sons Ltd.

Stimulation of inorganic pyrophosphate elaboration by cultured cartilage and chondrocytes.

PubMed

Ryan, L M; Kurup, I; Rosenthal, A K; McCarty, D J

1989-08-01

Inorganic pyrophosphate elaboration by articular cartilage may favor calcium pyrophosphate dihydrate crystal deposition. Frequently crystal deposits form in persons affected with metabolic diseases. The cartilage organ culture system was used to model these metabolic conditions while measuring the influence on extracellular pyrophosphate elaboration. Alterations of ambient pH, thyroid stimulating hormone levels, and parathyroid hormone levels did not change pyrophosphate accumulation in the media. However, subphysiologic ambient calcium concentrations (25, 100, 500 microM) increased pyrophosphate accumulation about chondrocytes 3- to 10-fold. Low calcium also induced release of [14C]adenine-labeled nucleotides from chondrocytes, potential substrates for generation of extracellular pyrophosphate by ectoenzymes. Exposing cartilage to 10% fetal bovine serum also enhanced by 50% the egress of inorganic pyrophosphate from the tissue.

A simple turn on fluorescent sensor for the selective detection of thiamine using coconut water derived luminescent carbon dots.

PubMed

Purbia, Rahul; Paria, Santanu

2016-05-15

In this study microwave-assisted hydrothermal method was used to prepare highly luminescent carbon dots (1-6 nm size) within a minute from tender coconut (Cocos nucifera) water. The synthesized carbon dots (C-dots) exhibit emission of blue and green lights while excited at 390 and 450 nm wavelengths, respectively. As an application, these C-dots were tested for a simple "turn on" fluorescent sensor for rapid detection of thiamine (vitamin B1). The detection of thiamine in human body is very important to prevent various diseases such as beriberi, neurological disorders, optic neuropathy, etc. The fluorescence emission intensity of C-dots quenches after addition of Cu(2+) ion and then again increases selectively (turn on) after the addition of thiamine. The fluorescence emission intensity enhancement of Cu(2+) ion modified C-dots in the presence of thiamine exhibits a linear relationship within the thiamine concentration range of 10-50 μM. The limit of detection was found to be 280 nM from this study. The selectivity of the detection was also tested in the presence of different organic molecules and inorganic ions (Ca(2+), Mg(2+), Na(+), K(+), Cl(-), SO4(2-), and NO3(-)) which are present in blood serum and urine and found to be almost no interference in the detection. Finally, to see the applicability in real samples a commercial vitamin capsule was tested and found less than 3% error in the detected concentration. The C-dots were also used for bioimaging of fungus and the results show they are also suitable for this application too. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardiac structural changes and electrical remodeling in a thiamine-deficiency model in rats.

PubMed

Roman-Campos, D; Campos, A C; Gioda, C R; Campos, P P; Medeiros, M A A; Cruz, J S

2009-06-05

Thiamine is an important cofactor present in many biochemical reactions, and its deprivation can lead to heart dysfunction. Little is known about the influence of thiamine deprivation on the electrophysiological behavior of the isolated heart cells and information about thiamine deficiency in heart morphology is controversial. Thus, we decided to investigate the major repolarizing conductances and their influence in the action potential (AP) waveform as well as the changes in the heart structure in a set of thiamine deficiency in rats. Using the patch-clamp technique, we investigated inward (I(K1)) and outward K(+) currents (I(to)), T-type and L-type Ca(2+) currents and APs. To evaluate heart morphology we used hematoxylin and eosin in transversal heart sections. Thiamine deficiency caused a marked decrease in left ventricle thickness, cardiomyocyte number, cell length and width, and membrane capacitance. When evaluating I(to) we did not find difference in current amplitude; however an acceleration of I(to) inactivation was observed. I(K1) showed a reduction in the amplitude and slope conductance, which implicated a less negative resting membrane potential in cardiac myocytes isolated from thiamine-deficient rats. We did not find any difference in L-type Ca(2+) current density. T-type Ca(2+) current was not observed. In addition, we did not observe significant changes in AP repolarization. Based on our study we can conclude that thiamine deficiency causes heart hypotrophy and not heart hypertrophy. Moreover, we provided evidence that there is no major electrical remodeling during thiamine deficiency, a feature of heart failure models.

The effects of thiamin on lead metabolism: organ distribution of lead 203.

PubMed Central

Kim, J S; Hamilton, D L; Blakley, B R; Rousseaux, C G

1992-01-01

The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy. PMID:1423063

Thiamine deficiency effects on the vision and foraging ability of lake trout fry

USGS Publications Warehouse

Tillitt, Donald E.; Zajicek, James L.; Claunch, Rachel; Honeyfield, Dale C.; Fitzsimons, John D.; Brown, Scott B.

2008-01-01

The exact causes of the historical recruitment failures of Great Lakes lake trout Salvelinus namaycush are unknown. Thiamine deficiency has been associated with neurological abnormalities in lake trout that lead to early mortality syndrome (EMS) in salmonine swim-up fry, and EMS-related mortality at the swim-up stage is a factor that contributes to the reproductive failure of lake trout populations in the Great Lakes. The potential for adverse effects of thiamine deficiency beyond the swim-up stage is unknown. We investigated the effects of low egg thiamine on behavioral functions in young, post-swim-up lake trout fry. The behavioral endpoints included visual acuity and prey capture rates in the same groups of lake trout fry from each family. Low-thiamine eggs were produced by feeding lake trout broodstock diets entailing thiaminase activity. The thiamine content of the spawned eggs ranged from 0.3 to 26.1 nmol/g. Both visual acuity and prey capture rates were affected by the thiamine content of the eggs. The visual acuity of lake trout was severely affected by low egg thiamine, mainly at thiamine concentrations below the threshold of 0.8 nmol/g but also at higher concentrations in field-collected eggs. Feeding was also reduced with low egg thiamine content. The reduction of prey capture rates was dramatic below 0.8 nmol/g and less dramatic, but still significant, in a portion of the families with egg thiamine concentrations of less than 5.0 nmol/g from both laboratory and field samples. Approximately one-third of the latter families had reduced feeding rates. Deficits in visual acuity may be part of the mechanism leading to decreased feeding rates in these fry. The effects of low egg thiamine on both of the behavioral endpoints studied increase the risk of low recruitment rates in Great Lakes lake trout populations.

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium...

The connection between maternal thiamine shortcoming and offspring cognitive damage and poverty perpetuation in underprivileged communities across the world.

PubMed

Dias, Fernando M V; Silva, Danielle Marra de Freitas; Doyle, Flavia Costa de Proença; Ribeiro, Angela Maria

2013-01-01

The acquisition of cognitive, sensory-motor and social emotional functions depend on a proper development of the Central Nervous System (CNS). This set of functions, known as intelligence, allows a better adaptation to the environment. In the last decades, an increase in the average of intelligence has been reported. However, such an increase cannot be observed in an equivalent way in economically and social underprivileged regions. Children from those regions are in great risk of being affected by mental retardation or impaired cognitive development. In later life they will, probably, be unable to transform and improve themselves and their communities, perpetuating the poverty of the region. Therefore, knowledge of factors involved in CNS development is a matter of health closely related to social improvement. Malnutrition throughout pregnancy and breastfeeding is clearly identifiable as a cause of damage in CNS development. Vitamin B1 (Thiamine) is a micronutrient important to the growth and maturity of the CNS. Thiamine shortcoming may affect 50% of pregnant women. Thiamine function in cerebral development is still not well known. There is a gap in the literature regarding systematical research about the blood thiamine concentration throughout the periods of gestation and breastfeeding. These studies are relevant in populations with a high level of nutritional vulnerability, because in a follow up offspring cognitive exam they could reveal if the maternal thiamine deficiency is related to child CNS impairment. This paper introduce the hypothesis that thiamine shortcoming during pregnancy and breastfeeding is directly related to cognitive impairment of child. Data about the neurophysiological role of thiamine, consequences of its shortcoming in experimental models, populations under the risk of thiamine shortcoming are presented. The hypothesis that maternal thiamine shortcoming causes damage related to child cognitive development needs to be considered. Thus

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis.

PubMed

Moskowitz, Ari; Graver, Amanda; Giberson, Tyler; Berg, Katherine; Liu, Xiaowen; Uber, Amy; Gautam, Shiva; Donnino, Michael W

2014-02-01

Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA. This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels. Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = -0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002). Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted. © 2013.

Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin

PubMed Central

Meyer, Danilo; Neumann, Piotr; Koers, Eline; Sjuts, Hanno; Lüdtke, Stefan; Sheldrick, George M.; Ficner, Ralf; Tittmann, Kai

2012-01-01

Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 Å resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than π-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms. PMID:22730460

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis⋆

PubMed Central

Moskowitz, Ari; Graver, Amanda; Giberson, Tyler; Berg, Katherine; Liu, Xiaowen; Uber, Amy; Gautam, Shiva; Donnino, Michael W.

2013-01-01

Purpose Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA. Materials and Methods This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels. Results Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = −0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002). Conclusions Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted. PMID:23993771

Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models.

PubMed

Bunik, Victoria I; Tylicki, Adam; Lukashev, Nikolay V

2013-12-01

Bringing a knowledge of enzymology into research in vivo and in situ is of great importance in understanding systems biology and metabolic regulation. The central metabolic significance of thiamin (vitamin B1 ) and its diphosphorylated derivative (thiamin diphosphate; ThDP), and the fundamental differences in the ThDP-dependent enzymes of metabolic networks in mammals versus plants, fungi and bacteria, or in health versus disease, suggest that these enzymes are promising targets for biotechnological and medical applications. Here, the in vivo action of known regulators of ThDP-dependent enzymes, such as synthetic structural analogs of the enzyme substrates and thiamin, is analyzed in light of the enzymological data accumulated during half a century of research. Mimicking the enzyme-specific catalytic intermediates, the phosphonate analogs of 2-oxo acids selectively inhibit particular ThDP-dependent enzymes. Because of their selectivity, use of these compounds in cellular and animal models of ThDP-dependent enzyme malfunctions improves the validity of the model and its predictive power when compared with the nonselective and enzymatically less characterized oxythiamin and pyrithiamin. In vitro studies of the interaction of thiamin analogs and their biological derivatives with potential in vivo targets are necessary to identify and attenuate the analog selectivity. For both the substrate and thiamin synthetic analogs, in vitro reactivities with potential targets are highly relevant in vivo. However, effective concentrations in vivo are often higher than in vitro studies would suggest. The significance of specific inihibition of the ThDP-dependent enzymes for the development of herbicides, antibiotics, anticancer and neuroprotective strategies is discussed. © 2013 FEBS.

Abolition of reperfusion-induced arrhythmias in hearts from thiamine-deficient rats.

PubMed

Oliveira, Fernando A; Guatimosim, Silvia; Castro, Carlos H; Galan, Diogo T; Lauton-Santos, Sandra; Ribeiro, Angela M; Almeida, Alvair P; Cruz, Jader S

2007-07-01

Extensive work has been done regarding the impact of thiamine deprivation on the nervous system. In cardiac tissue, chronic thiamine deficiency is described to cause changes in the myocardium that can be associated with arrhythmias. However, compared with the brain, very little is known about the effects of thiamine deficiency on the heart. Thus this study was undertaken to explore whether thiamine deprivation has a role in cardiac arrhythmogenesis. We examined hearts isolated from thiamine-deprived and control rats. We measured heart rate, diastolic and systolic tension, and contraction and relaxation rates. Whole cell voltage clamp was performed in rat isolated cardiac myocytes to measure L-type Ca(2+) current. In addition, we investigated the global intracellular calcium transients by using confocal microscopy in the line-scan mode. The hearts from thiamine-deficient rats did not degenerate into ventricular fibrillation during 30 min of reperfusion after 15 min of coronary occlusion. The antiarrhythmogenic effects were characterized by the arrhythmia severity index. Our results suggest that hearts from thiamine-deficient rats did not experience irreversible arrhythmias. There was no change in L-type Ca(2+) current density. Inactivation kinetics of this current in Ca(2+)-buffered cells was retarded in thiamine-deficient cardiac myocytes. The global Ca(2+) release was significantly reduced in thiamine-deficient cardiac myocytes. The amplitude of caffeine-releasable Ca(2+) was lower in thiamine-deficient myocytes. In summary, we have found that thiamine deprivation attenuates the incidence and severity of postischemic arrhythmias, possibly through a mechanism involving a decrease in global Ca(2+) release.

Household Consumption of Thiamin-Fortified Fish Sauce Increases Erythrocyte Thiamin Concentrations among Rural Cambodian Women and Their Children Younger Than 5 Years of Age: A Randomized Controlled Efficacy Trial.

PubMed

Whitfield, Kyly C; Karakochuk, Crystal D; Kroeun, Hou; Sokhoing, Ly; Chan, Benny B; Borath, Mam; Sophonneary, Prak; Moore, Kirsten; Tong, Jeffery K T; McLean, Judy; Talukder, Aminuzzaman; Lynd, Larry D; Li-Chan, Eunice C Y; Kitts, David D; Green, Tim J

2017-02-01

To assess whether ad libitum consumption of thiamin-fortified fish sauce over 6 months yields higher erythrocyte thiamin diphosphate concentrations (eTDP) among women of childbearing age and their children aged 12-59 months compared with control sauce containing no thiamin. In this double-blind, randomized controlled efficacy trial, 276 nonpregnant, nonlactating women (18-45 years of age) and their families in Prey Veng, Cambodia, were randomized to receive 1 of 3 fish sauce formulations: low thiamin concentration (low, 2 g/L), high thiamin concentration (high, 8 g/L), or a control (no thiamin) fish sauce. Baseline (t = 0) and endline (t = 6 months) eTDP were measured with the use of high-performance liquid chromatography with a fluorescence detector. Fish sauce consumption did not differ between treatment groups (P = .19). In intent-to-treat analysis, women's baseline-adjusted endline eTDP (mean; 95% CI) was higher among women in the low (259; 245-274 nmol/L) and high (257; 237-276 nmol/L) groups compared with control (184; 169-198 nmol/L; P < .001); low and high groups did not differ (P = .83). Similarly, children's baseline-adjusted eTDP was higher in the low (259; 246-271 nmol/L) and high (257; 243-270 nmol/L) groups compared with control (213; 202-224 nmol/L; P < .001). Fortified fish sauce appears to be an efficacious means of improving biochemical thiamin status in nonpregnant, nonlactating women and their children (1-5 years of age) living in rural Cambodia. ClinicalTrials.gov: NCT02221063. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness and retention of thiamine and its analogs administered to steelhead and landlocked Atlantic salmon

USGS Publications Warehouse

Ketola, H.G.; Isaacs, G.R.; Robins, J.S.; Lloyd, R.C.

2008-01-01

We investigated the feasibility of enhancing the reproduction of steelhead Oncorhynchus mykiss and landlocked Atlantic salmon Salmo salar in lakes where the consumption of alewives Alosa pseudoharengus and other forage fishes containing thiaminase can cause them to become thiamine deficient and thereby reduce the survival of their fry. We evaluated feeding fingerling steelhead excess thiamine hydrochloride (THCl) for 1 or 2 weeks or equimolar amounts of thiamine mononitrate, thiamine-tetrahydrofurfuryl-disulfide, benfotiamine, or dibenzoyl thiamine (DBT). We found minimal internal reserves of thiamine after 6 months. We also compared the ability of injections of thiamine and its analogs to prevent mortality in thiamine-deficient steelhead and Atlantic salmon sac fry and found all forms to be effective, although benfotiamine was the least effective on an equimolar basis. Further, we injected yearling steelhead and found that DBT was tolerated at approximately 11,200 nmol/g of body weight, about 10 times more than thiamine in any other form. When yearling steelhead were injected with near-maximal doses of thiamine hydrochloride and several analogs and then fed a thiamine-deficient diet, DBT was retained for approximately 2 years - in contrast to other forms, which were retained for less than about 6 months. Therefore, these results suggest that neither feeding nor injecting young hatchery salmonids with DBT is likely to enhance their reproduction for more than 2 years after stocking. However, injecting DBT in nearly mature fish (either cultured fish from hatcheries or wild fish captured in lakes) may provide them with enough thiamine to successfully spawn within 2 years even though they consume mainly thiaminase-containing forage fishes. ?? Copyright by the American Fisheries Society 2008.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

PubMed

Donnino, Michael W; Andersen, Lars W; Chase, Maureen; Berg, Katherine M; Tidswell, Mark; Giberson, Tyler; Wolfe, Richard; Moskowitz, Ari; Smithline, Howard; Ngo, Long; Cocchi, Michael N

2016-02-01

To determine if intravenous thiamine would reduce lactate in patients with septic shock. Randomized, double-blind, placebo-controlled trial. Two US hospitals. Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Dissolution behaviour of ferric pyrophosphate and its mixtures with soluble pyrophosphates: Potential strategy for increasing iron bioavailability.

PubMed

Tian, Tian; Blanco, Elena; Smoukov, Stoyan K; Velev, Orlin D; Velikov, Krassimir P

2016-10-01

Ferric pyrophosphate (FePP) is a widely used iron source in food fortification and in nutritional supplements, due to its white colour, that is very uncommon for insoluble Fe salts. Although its dissolution is an important determinant of Fe adsorption in human body, the solubility characteristics of FePP are complex and not well understood. This report is a study on the solubility of FePP as a function of pH and excess of pyrophosphate ions. FePP powder is sparingly soluble in the pH range of 3-6 but slightly soluble at pH<2 and pH>8. In the presence of pyrophosphate ions the solubility of FePP strongly increases at pH 5-8.5 due to formation a soluble complex between Fe(III) and pyrophosphate ions, which leads to an 8-10-fold increase in the total ionic iron concentration. This finding is beneficial for enhancing iron bioavailability, which important for the design of fortified food, beverages, and nutraceutical products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between thiamine and subacute ruminal acidosis induced by a high-grain diet in dairy cows.

PubMed

Pan, X H; Yang, L; Xue, F G; Xin, H R; Jiang, L S; Xiong, B H; Beckers, Y

2016-11-01

Two experiments were conducted to reveal the effects of grain-induced subacute rumen acidosis (SARA) on thiamine status in blood and rumen fluid in dairy cows. In both experiments, 6 multiparous, rumen-fistulated Holstein dairy cows were used in a 2-treatment, 2-period crossover design. Each experimental period consisted of 21d (total of 42d). Experiment 1 was to investigate the effects of SARA on thiamine status in blood and rumen fluid. Treatments were either control (20% starch, dry matter basis) or SARA-inducing diet (SAID, 33.2% starch, dry matter basis). In experiment 2, the effects of dietary thiamine supplementation on attenuating SARA and ruminal fermentation characteristics in dairy cows were studied. All cows received the same SAID diet during the whole experimental period; treatments were with or without thiamine (180mg of thiamine/kg of dry matter intake). In both experiments, rumen fluid samples were collected at 0, 3, 6, 9, and 12h after morning feeding on d 21 and 42 of the experiments for measurement of pH, thiamine, volatile fatty acid, and lactate contents. Peripheral blood was also collected at 3h after morning feeding on d 21 and 42 to measure thiamine, carbohydrate metabolites, and enzyme activities. In experiment 1, cows fed the SAID diet had lower ruminal and plasma thiamine concentrations and higher lactate than cows fed the control diet. The ruminal thiamine contents were positively related to pH and the concentrations of acetate in the rumen, and negatively correlated with the lactate contents. Experiment 2 demonstrated that ruminal pH and the concentrations of thiamine, acetate, and total volatile fatty acids in the rumen were increased, whereas ruminal lactate contents were reduced by thiamine supplementation. The concentrations of lactate and the activity of lactate dehydrogenase in blood were reduced in the thiamine supplemented group, and the opposite was true for the nonesterified fatty acids and α-ketoneglutarate dehydrogenase

Thiamine in septic shock patients with alcohol use disorders: An observational pilot study.

PubMed

Holmberg, Mathias Johan; Moskowitz, Ari; Patel, Parth Vijay; Grossestreuer, Anne Victoria; Uber, Amy; Stankovic, Nikola; Andersen, Lars Wiuff; Donnino, Michael William

2018-02-01

Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality. We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels≥4mmol/L. We excluded those who received thiamine later than 48h of sepsis onset. We included 53 patients. Thirty-four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p=0.02. A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of thiamine on reproduction of Atlantic salmon and a new hypothesis for their extirpation in Lake Ontario

USGS Publications Warehouse

Ketola, H. George; Bowser, Paul R.; Wooster, Gregory A.; Wedge, Leslie R.; Hurst, Steven S.

2000-01-01

Previous researchers demonstrated that a mortality in fry (called Cayuga syndrome) of Atlantic salmon Salmo salar from Cayuga Lake (New York) was associated with low levels of thiamine. They reduced the mortality of fry by bathing or injecting fry with thiamine. We injected four to six gravid female Atlantic salmon with either physiological saline (PS) or PS plus thiamine (7 mg/kg weight) 14–23 d before eggs were stripped, fertilized, and incubated in individual lots. Chemical analyses showed that eggs from control and treated salmon contained 1.1 and 1.6 nmol thiamine/g, respectively. Thiamine injections had no significant effect on the percentage of eggs that hatched. Between 700 and 800 Celius degree-days postfertilization, control fry (saline) showed signs of Cayuga syndrome and a 45% incidence of mortality; in contrast, mortality was only 1.9% for fry that received thiamine. By 1,078 degree-days postfertilization, mean mortality of control fry was 98.6%, whereas that for thiamine-injected salmon was 2.1%. This study showed that thiamine injections of prespawning female salmon from Cayuga Lake increased thiamine content of their eggs and prevented the Cayuga syndrome and subsequent mortality of fry. Historically, overfishing, pollution, and building of dams and barriers to spawning migration were suggested as possible causes of the decline of the Atlantic salmon in Lake Ontario and Cayuga Lake. Based on our findings and other reports, we suggest another possible contributing cause of the extirpation of landlocked Atlantic salmon in Lake Ontario and some other inland waters of New York: The entrance of alewives Alosa pseudoharengus containing thiaminase, which induced thiamine deficiency in eggs and increased mortality in fry of the predatory salmon.

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

PubMed

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

The characteristics of pyrophosphate: D-fructose-6-phosphate 1-phosphotransferases from Sansevieria trifasciata leaves and Phaseolus coccineus stems.

PubMed

Kowalczyk, S

1987-01-01

Three different molecular forms of pyrophosphate-dependent phosphofructokinase have been isolated: one from Sansevieria trifasciata leaves and two from Phaseolus coccineus stems. The form isolated from S. trifasciata has the molecular weight of about 115,000. The apparent molecular weights for the two forms from mung bean were approximately 220,000 and 450,000. All three forms have the same pH optima, an absolute requirement for Mg2+ ions both in the forward and reverse reaction, but differ in their sensitivity toward fructose 2,6-bisphosphate. Kinetic properties of the partially purified enzymes have been investigated in the presence and absence of fructose 2,6-bisphosphate. Pyrophosphate-dependent phosphofructokinase from S. trifasciata exhibited hyperbolic kinetics with all substrates tested. The saturation curves of the enzyme (form A) from mung bean for pyrophosphate, fructose 6-phosphate and fructose 1,6-bisphosphate were sigmoidal in the absence of fructose 2,6-bisphosphate. In the presence of fructose 2,6-bisphosphate these kinetics became hyperbolic.

Formation of pyrophosphate on hydroxyapatite with thioesters as condensing agents

NASA Technical Reports Server (NTRS)

Weber, A. L.

1982-01-01

'Energy-rich' thioesters are shown to act as condensing agents in the formation of pyrophosphate on hydroxyapatite in the presence of water at ambient temperature. The yield of pyrophosphate based on thioester ranges from 2.5% to 11.4% and depends upon the pH and concentration of reactants. Reaction of 0.130 M hydroxyapatite suspended in a solution of 0.08 M sodium phosphate and 0.20 M imidazole hydrochloride (pH 7.0) with 0.10 M N,S-diacetylcysteamine for 6 days gives the highest yield of pyrophosphate (11.4%). Pyrophosphate formation requires the presence of hydroxyapatite, sodium phosphate and the thioester, N,S-diacetylcysteamine. The related thioester, N,S-diacetylcysteine, also yields pyrophosphate in reactions on hydroxyapatite.

Human 2-Oxoglutarate Dehydrogenase Complex E1 Component Forms a Thiamin-derived Radical by Aerobic Oxidation of the Enamine Intermediate*

PubMed Central

Nemeria, Natalia S.; Ambrus, Attila; Patel, Hetalben; Gerfen, Gary; Adam-Vizi, Vera; Tretter, Laszlo; Zhou, Jieyu; Wang, Junjie; Jordan, Frank

2014-01-01

Herein are reported unique properties of the human 2-oxoglutarate dehydrogenase multienzyme complex (OGDHc), a rate-limiting enzyme in the Krebs (citric acid) cycle. (a) Functionally competent 2-oxoglutarate dehydrogenase (E1o-h) and dihydrolipoyl succinyltransferase components have been expressed according to kinetic and spectroscopic evidence. (b) A stable free radical, consistent with the C2-(C2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (ThDP) cation radical was detected by electron spin resonance upon reaction of the E1o-h with 2-oxoglutarate (OG) by itself or when assembled from individual components into OGDHc. (c) An unusual stability of the E1o-h-bound C2-(2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (the “ThDP-enamine”/C2α-carbanion, the first postdecarboxylation intermediate) was observed, probably stabilized by the 5-carboxyl group of OG, not reported before. (d) The reaction of OG with the E1o-h gave rise to superoxide anion and hydrogen peroxide (reactive oxygen species (ROS)). (e) The relatively stable enzyme-bound enamine is the likely substrate for oxidation by O2, leading to the superoxide anion radical (in d) and the radical (in b). (f) The specific activity assessed for ROS formation compared with the NADH (overall complex) activity, as well as the fraction of radical intermediate occupying active centers of E1o-h are consistent with each other and indicate that radical/ROS formation is an “off-pathway” side reaction comprising less than 1% of the “on-pathway” reactivity. However, the nearly ubiquitous presence of OGDHc in human tissues, including the brain, makes these findings of considerable importance in human metabolism and perhaps disease. PMID:25210035

Enhanced Photolysis of Nucleic Acid Monomers by Pyrophosphate in the Simulated Primitive Soup

NASA Astrophysics Data System (ADS)

Kongjiang, Wang; Zhifang, Chai; Xianming, Pan

1999-05-01

In our simulation of the photochemistry of the primitive soup, it was found that yield of chromophore loss of some nucleic acid bases, nucleosides and nucleotides [NA] undergoing ultraviolet radiation by medium pressure mercury lamp [MPML] was enhanced by pyrophosphate and triphosphate whether O2 is present or not. The yield of chromophore loss of guanosine, uracil, 5' CMP, and the derivatives of adenine and thymine was observed to rise with the increase of molar concentration of pyrophosphate in N2-saturated systems. In air-saturated samples, increase in yield of chromophore loss was observed when the concentration of pyrophosphate reaches 5×10-4 M, relative yield of chromophore loss (CLrel) coming to maximum in the range from 0.01 to 0.1 M, followed by a slight decline with the further increase of pyrophosphate concentration. The enhancement of photolysis of NA by pyrophosphate was due to the interaction between NA and pyrophosphate radicals photoionized by UV quanta of wavelength less than about 210 nm in the emission spectrum of a MPML. The relevance of this phenomenon to the origin of life has been discussed as well.

Industrial fuel ethanol yeasts contain adaptive copy number changes in genes involved in vitamin B1 and B6 biosynthesis.

PubMed

Stambuk, Boris U; Dunn, Barbara; Alves, Sergio L; Duval, Eduarda H; Sherlock, Gavin

2009-12-01

Fuel ethanol is now a global energy commodity that is competitive with gasoline. Using microarray-based comparative genome hybridization (aCGH), we have determined gene copy number variations (CNVs) common to five industrially important fuel ethanol Saccharomyces cerevisiae strains responsible for the production of billions of gallons of fuel ethanol per year from sugarcane. These strains have significant amplifications of the telomeric SNO and SNZ genes, which are involved in the biosynthesis of vitamins B6 (pyridoxine) and B1 (thiamin). We show that increased copy number of these genes confers the ability to grow more efficiently under the repressing effects of thiamin, especially in medium lacking pyridoxine and with high sugar concentrations. These genetic changes have likely been adaptive and selected for in the industrial environment, and may be required for the efficient utilization of biomass-derived sugars from other renewable feedstocks.

Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis.

PubMed

Maiorana, Arianna; Vergine, Gianluca; Coletti, Valentina; Luciani, Matteo; Rizzo, Cristiano; Emma, Francesco; Dionisi-Vici, Carlo

2014-01-01

Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses. We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction. A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses. Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly

Thiamine and its phosphate esters in relation to cardiometabolic risk factors in Saudi Arabs.

PubMed

Al-Daghri, Nasser M; Al-Attas, Omar S; Alkharfy, Khalid M; Alokail, Majed S; Abd-Alrahman, Sherif H; Sabico, Shaun

2013-09-23

Thiamine deficiency has suggested to be linked to several insulin-resistance complications. In this study, we aim to associate circulating thiamine levels among cardiometabolic parameters in an Arab cohort using a simple, sensitive, rapid and selective high-performance liquid chromatography (HPLC) method that has recently been developed. A total of 236 randomly selected, consenting Saudi adult participants (166 males and 70 females) were recruited and screened for the presence of the metabolic syndrome (MetS) using the modified National Cholesterol Education Program-Adult Treatment Panel III definition. Blood thiamine and its derivatives were quantified using HPLC. A total of 140 participants (53.9%) had MetS. The levels of thiamine and its derivatives of those with MetS were not significantly different from those without. However, hypertensive subjects had significantly higher urinary thiamine (P = 0.03) as well as significantly lower levels of thiamine diphosphate (TDP) (P = 0.01) and total thiamine (P = 0.02) than the normotensive subjects, even after adjusting for age and body mass index (BMI). Furthermore, age- and BMI-matched participants with elevated blood glucose levels had significantly lower levels of thiamine monophosphate (P = 0.020), TDP (P < 0.001) and total thiamine (P < 0.001) and significantly elevated levels of urinary thiamine (P = 0.005) compared to normoglycemic participants. Low thiamine levels are associated with elevated blood glucose and hypertension in Saudi adults. Determination of thiamine status may be considered and corrected among patients with, or at high risk for, MetS, but the question whether thiamine deficiency correction translates to improved cardiometabolic status needs further longitudinal investigation.

Thiamine and its phosphate esters in relation to cardiometabolic risk factors in Saudi Arabs

PubMed Central

2013-01-01

Background Thiamine deficiency has suggested to be linked to several insulin-resistance complications. In this study, we aim to associate circulating thiamine levels among cardiometabolic parameters in an Arab cohort using a simple, sensitive, rapid and selective high-performance liquid chromatography (HPLC) method that has recently been developed. Methods A total of 236 randomly selected, consenting Saudi adult participants (166 males and 70 females) were recruited and screened for the presence of the metabolic syndrome (MetS) using the modified National Cholesterol Education Program–Adult Treatment Panel III definition. Blood thiamine and its derivatives were quantified using HPLC. Results A total of 140 participants (53.9%) had MetS. The levels of thiamine and its derivatives of those with MetS were not significantly different from those without. However, hypertensive subjects had significantly higher urinary thiamine (P = 0.03) as well as significantly lower levels of thiamine diphosphate (TDP) (P = 0.01) and total thiamine (P = 0.02) than the normotensive subjects, even after adjusting for age and body mass index (BMI). Furthermore, age- and BMI-matched participants with elevated blood glucose levels had significantly lower levels of thiamine monophosphate (P = 0.020), TDP (P < 0.001) and total thiamine (P < 0.001) and significantly elevated levels of urinary thiamine (P = 0.005) compared to normoglycemic participants. Conclusions Low thiamine levels are associated with elevated blood glucose and hypertension in Saudi adults. Determination of thiamine status may be considered and corrected among patients with, or at high risk for, MetS, but the question whether thiamine deficiency correction translates to improved cardiometabolic status needs further longitudinal investigation. PMID:24059534

Thiamine Deficiency Complex Workshop final report: November 6-7, 2008, Ann Arbor, MI

USGS Publications Warehouse

Honeyfield, Dale C.; Tillitt, Donald E.; Riley, Stephen C.

2008-01-01

Fry mortality which was first observed in the late 1960s in Great Lakes salmonines and in Baltic Sea salmon in 1974 has now been linked to thiamine deficiency (historically referred to as Early Mortality Syndrome, or EMS and M74, respectively). Over the past 14 years significant strides have been made in our understanding of this perplexing problem. It is now known that thiamine deficiency causes embryonic mortality in these salmonids. Both overt mortality and secondary effects of thiamine deficiency are observed in juvenile and adult animals. Collectively the morbidity and mortality (fry and adult mortality, secondary metabolic and behavior affects in juveniles and adult fish) are referred to as Thiamine Deficiency Complex (TDC). A workshop was held in Ann Arbor, MI on 6-7 November 2008 that brought together 38 federal, state, provincial, tribal and university scientists to share information, present data and discuss the latest observations on thiamine status of aquatic animals with thiamine deficiency and the causative agent, thiaminase. Twenty presentations (13 oral and 7 posters) detailed current knowledge. In Lake Huron, low alewife Alosa pseudoharengus abundance has persisted and egg thiamine concentrations in salmonines continue to increase, along with evidence of natural reproduction in lake trout Salvelinus namaycush. Lake Michigan Chinook salmon Oncorhynchus tshawytscha appear to have a lower thiamine requirement than other salmonids in the lake. Lake Ontario American eel Anguilla rostrata foraging on alewife have approximately one third the muscle thiamine compared to eels not feeding on alewife, suggesting that eels may be suffering from thiamine deficiency. Secondary effects of low thiamine exist in Great Lakes salmonines and should not be ignored. Thiaminase activity in dreissenid mussels is extremely high but a connection to TDC has not been made. Thiaminase in net plankton was found more consistently in lakes Michigan and Ontario than other lakes

Egg thiamine status of Lake Ontario salmonines 1995-2004 with emphasis on lake trout

USGS Publications Warehouse

Fitzsimons, J.D.; Williston, B.; Williston, G.; Brown, L.; El-Shaarawi, A.; Vandenbyllaardt, L.; Honeyfeld, D.; Tillitt, D.; Wolgamood, M.; Brown, S.B.

2007-01-01

Alewives (Alosa pseudoharengus), the major prey fish for Lake Ontario, contain thiaminase. They are associated with development of a thiamine deficiency in salmonines which greatly increases the potential for developing an early mortality syndrome (EMS). To assess the possible effects of thiamine deficiency on salmonine reproduction we measured egg thiamine concentrations for five species of Lake Ontario salmonines. From this we estimated the proportion of families susceptible to EMS based on whether they were below the ED20, the egg thiamine concentration associated with 20% mortality due to EMS. The ED20s were 1.52, 2.63, and 2.99 nmol/g egg for Chinook salmon (Oncorhynchus tshawytscha), lake trout (Salvelinus namaycush), and coho salmon (Oncorhynchus kisutch), respectively. Based on the proportion of fish having egg thiamine concentrations falling below the ED20, the risk of developing EMS in Lake Ontario was highest for lake trout, followed by coho (O. kisutch), and Chinook salmon, with the least risk for rainbow trout (O. mykiss). For lake trout from western Lake Ontario, mean egg thiamine concentration showed significant annual variability during 1994 to 2003, when the proportion of lake trout at risk of developing EMS based on ED20 ranged between 77 and 100%. Variation in the annual mean egg thiamine concentration for western Lake Ontario lake trout was positively related (p < 0.001, r2 = 0.94) with indices of annual adult alewife biomass. While suggesting the possible involvement of density-dependent changes in alewives, the changes are small relative to egg thiamine concentrations when alewife are not part of the diet and are of insufficient magnitude to allow for natural reproduction by lake trout.

FGF2 Stimulation of the Pyrophosphate-Generating Enzyme, PC-1, in Pre-Osteoblast Cells Is Mediated by RUNX2

PubMed Central

Hatch, Nan E; Li, Yan; Franceschi, Renny T

2009-01-01

Pyrophosphate is an established inhibitor of hydroxyapatite deposition and crystal growth, yet when hydrolyzed into phosphate, it becomes a substrate for hydroxyapatite deposition. Pyrophosphate-generating enzyme (PC-1), Ank, and tissue nonspecific alkaline phosphatase (Tnap) are three factors that regulate extracellular pyrophosphate levels through its generation, transport, and hydrolysis. We previously showed that fibroblast growth factor 2 (FGF2) induces PC-1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre-osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre-osteoblast cultures. In contrast to Ank and Tnap that are regulated by FGF2 in multiple cell types, we found regulation of PC-1 to be selective to pre-osteoblastic cells and to require the osteoblast-related transcription factor, Runx2. Specifically, FGF2 was unable to induce PC-1 expression in Runx2-negative nonbone cells or in calvarial cells from Runx2-deficient mice. Transfection of these cells with a Runx2 expression vector restored FGF2 responsiveness. FGF2 was also shown to stimulate recruitment of Runx2 to the endogenous PC-1 promoter in MC3T3E1(C4) cells, as measured by chromatin immunoprecipitation. Taken together, our results establish that FGF2 is a specific inducer of PC-1 in pre-osteoblast cells and that FGF2 induces PC-1 expression through a mechanism involving Runx2. PMID:19049325

Study of orthophosphate, pyrophosphate, and pyrophosphatase in saliva with reference to calculus formation and inhibition.

PubMed

Pradeep, A R; Agarwal, Esha; P, Arjun Raju; Rao, M S Narayana; Faizuddin, Mohamed

2011-03-01

A large amount of calculus may hamper the efficacy of daily oral hygiene and thereby accelerate plaque formation. Salivary concentrations of orthophosphate and pyrophosphate are important in preventing calculus formation. Activity of orthophosphate, pyrophosphate, and pyrophosphatase was studied in whole saliva in calculus-forming groups and plaque-forming groups. The material for this study consists of 60 healthy individuals (age range: 15 to 30 years; mean age: 22 years). Depending on calculus index score, individuals were divided into four groups, each of 15 patients: Group 1, calculus index score 0 to 0.6; Group 2, calculus index score 0.7 to 1.8; Group 3, calculus index score 1.9 to 3; and Group 4, plaque group where index varied from 0 to 3. The saliva was collected and biochemically analyzed for concentration of orthophosphate, pyrophosphate, and pyrophosphatase. The mean values of orthophosphate in Groups 1, 2, 3, and 4 were 0.2559, 1.3639, 1.7311, and 0.1868 mM, respectively. The mean values of pyrophosphate in Groups 1, 2, 3, and 4 were 0.3258, 0.1091, 0.0314, and 0.3860 mM, respectively. The mean values of pyrophosphatase in Groups 1, 2, 3, and 4 were 10.7937, 15.4249, 27.2900, and 7.5427 units/ml, respectively. A holistic approach toward the control of periodontal disease should include antiplaque and anticalculus agents. The results are conclusive that the components orthophosphate, pyrophosphate, and pyrophosphatase present in saliva have a very significant role to play in formation and inhibition of calculus. This study reinforces the idea of using pyrophosphate and newer bisphosphonates as potential anticalculus agents.

Industrial fuel ethanol yeasts contain adaptive copy number changes in genes involved in vitamin B1 and B6 biosynthesis

PubMed Central

Stambuk, Boris U.; Dunn, Barbara; Alves, Sergio L.; Duval, Eduarda H.; Sherlock, Gavin

2009-01-01

Fuel ethanol is now a global energy commodity that is competitive with gasoline. Using microarray-based comparative genome hybridization (aCGH), we have determined gene copy number variations (CNVs) common to five industrially important fuel ethanol Saccharomyces cerevisiae strains responsible for the production of billions of gallons of fuel ethanol per year from sugarcane. These strains have significant amplifications of the telomeric SNO and SNZ genes, which are involved in the biosynthesis of vitamins B6 (pyridoxine) and B1 (thiamin). We show that increased copy number of these genes confers the ability to grow more efficiently under the repressing effects of thiamin, especially in medium lacking pyridoxine and with high sugar concentrations. These genetic changes have likely been adaptive and selected for in the industrial environment, and may be required for the efficient utilization of biomass-derived sugars from other renewable feedstocks. PMID:19897511

Perinatal consumption of thiamine-fortified fish sauce in rural Cambodia. A randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, is a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine placing breastfed infants at risk of beriberi. The objective wa...

Reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency.

PubMed

Serrano, Mercedes; Rebollo, Mónica; Depienne, Christel; Rastetter, Agnès; Fernández-Álvarez, Emilio; Muchart, Jordi; Martorell, Loreto; Artuch, Rafael; Obeso, José A; Pérez-Dueñas, Belén

2012-09-01

Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive basal ganglia disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Two Spanish siblings with a biotin-responsive basal ganglia disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. The clinical features resolved rapidly after thiamine administration. Despite the rarity of thiamine transporter-2 deficiency, it should be suspected in patients with acute dystonia and basal ganglia injury, as thiamine can halt disease evolution and prevent further episodes. © 2012 Movement Disorder Society. Copyright © 2012 Movement Disorder Society.

Factors affecting a cyanogen bromide-based assay of thiamin.

PubMed

Wyatt, D T; Lee, M; Hillman, R E

1989-11-01

We analyzed extensively a modified thiochrome method for thiamin analysis. Acid phosphatase (EC 3.1.3.2) from potato was superior to either alpha-amylase or acid phosphatase from wheat germ as a dephosphorylating agent. Timing of cyanogen bromide exposure was important, but the assay had good precision and accuracy. The standard curve was linear from 10 to 3000 nmol/L. The within-run and between-run coefficients of variation for total thiamin in whole blood were 3.6% and 7.4%, respectively. Analytical recoveries for low, intermediate, and high additions of thiamin to whole blood were 93-109%. Sample yield was increased by 41% (+/- 29% SD) with pre-assay freezing. Samples were stable for two days at room temperature, for seven days when refrigerated, and for two years when frozen. Previously unreported interference was seen with penicillin derivatives, and with several commonly used diuretic and antiepileptic medications. This assay may be suitable for population screening; 200 samples could be analyzed weekly at a cost of +0.20 per sample.

Calcium pyrophosphate dihydrate gout and other crystal deposition diseases.

PubMed

Reginato, A J

1991-08-01

The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

ALKYL PYROPHOSPHATE METAL SOLVENT EXTRACTANTS AND PROCESS

DOEpatents

Long, R.L.

1958-09-30

A process is presented for the recovery of uranium from aqueous mineral acidic solutions by solvent extraction. The extractant is a synmmetrical dialkyl pyrophosphate in which the alkyl substituents have a chain length of from 4 to 17 carbon atoms. Mentioned as a preferred extractant is dioctyl pyrophosphate. The uranium is precipitated irom the organic extractant phase with an agent such as HF, fluoride salts. alcohol, or ammonia.

Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).

PubMed

Liang, Xiaomin; Chien, Huan-Chieh; Yee, Sook Wah; Giacomini, Marilyn M; Chen, Eugene C; Piao, Meiling; Hao, Jia; Twelves, Jolyn; Lepist, Eve-Irene; Ray, Adrian S; Giacomini, Kathleen M

2015-12-07

The biguanide metformin is widely used as first-line therapy for the treatment of type 2 diabetes. Predominately a cation at physiological pH's, metformin is transported by membrane transporters, which play major roles in its absorption and disposition. Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3). Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 ± 0.2 mM) and other cationic compounds (MPP(+) and famotidine). The uptake mechanism for hTHTR-2 was pH and electrochemical gradient sensitive. Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin. Species differences in the substrate specificity of THTR-2 between human and mouse orthologues were observed. Taken together, our data suggest that hTHTR-2 may play a role in the intestinal absorption and tissue distribution of metformin and other organic cations and that the transporter may be a target for drug-drug and drug-nutrient interactions.

Blood thiamine values in captive adult African lions (Panthera leo).

PubMed

Hoover, John P; DiGesualdo, Cynthia L

2005-09-01

Heparinized whole-blood samples from 22 adult African lions (Panthera leo) fed diets considered nutritionally adequate in 10 American Zoo and Aquarium Association member zoos in North America were provided for this study. Blood thiamine values were estimated using a standard microbiological assay method. The mean +/- standard deviation for blood thiamine values was 249.3 +/- 43.5 nmol/L with a range in values from 160 to 350 nmol/L after exclusion of one outlier. There were no differences (P > 0.05) in the mean blood thiamine values of male and female lions, or of lions that were over and under 10 yr of age. This range (160 to 350 nmol/L) is proposed as a reasonable estimate of the expected range in blood thiamine values for captive adult African lions as currently fed in North American zoos.

Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

USGS Publications Warehouse

Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

2008-01-01

An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

Paenibacillus thiaminolyticus is not the cause of thiamine deficiency impeding lake trout (Salvelinus namaycush) recruitment in the Great Lakes

USGS Publications Warehouse

Richter, Catherine A.; Evans, Allison N.; Wright-Osment, Maureen K.; Zajicek, James L.; Heppell, Scott A.; Riley, Stephen C.; Krueger, Charles C.; Tillitt, Donald E.

2012-01-01

Thiamine (vitamin B1) deficiency is a global concern affecting wildlife, livestock, and humans. In Great Lakes salmonines, thiamine deficiency causes embryo mortality and is an impediment to restoration of native lake trout (Salvelinus namaycush) stocks. Thiamine deficiency in fish may result from a diet of prey with high levels of thiaminase I. The discoveries that the bacterial species Paenibacillus thiaminolyticus produces thiaminase I, is found in viscera of thiaminase-containing prey fish, and causes mortality when fed to lake trout in the laboratory provided circumstantial evidence implicating P. thiaminolyticus. This study quantified the contribution of P. thiaminolyticus to the total thiaminase I activity in multiple trophic levels of Great Lakes food webs. Unexpectedly, no relationship between thiaminase activity and either the amount of P. thiaminolyticus thiaminase I protein or the abundance of P. thiaminolyticus cells was found. These results demonstrate that P. thiaminolyticus is not the primary source of thiaminase activity affecting Great Lakes salmonines and calls into question the long-standing assumption that P. thiaminolyticus is the source of thiaminase in other wild and domestic animals.

Treatment with thiamine hydrochloride and astaxanthine for the prevention of yolk-sac mortality in Baltic salmon fry (M74 syndrome).

PubMed

Koski, P; Pakarinen, M; Nakari, T; Soivio, A; Hartikainen, K

1999-09-14

Two practical methods are reported for treating feral Baltic salmon with thiamine hydrochloride against M74 syndrome (abnormally high yolk-sac fry mortality of the Baltic salmon). Both bathing of the yolk-sac fry in thiamine hydrochloride (1000 mg l-1, 1 h) and a single intraperitoneal injection given to the female brood fish (100 mg kg-1 fish) during the summer 3 mo before stripping were shown to elevate the whole body total thiamine concentration in the fry. Both treatments were also shown to be effective in preventing mortality due to M74 syndrome. The effect of bathing the yolk-sac fry was shown to be dose-dependent. The results support the view that there is a causal relationship between the thiamine status of the yolk-sac fry and M74 mortality. An intraperitoneal injection of astaxanthine suspension administered to the female brood fish (11 mg kg-1 fish) in the summer 3 mo before stripping elevated the astaxanthine concentration in the eggs but did not affect mortality due to M74 syndrome. An interaction between astaxanthine and thiamine may occur in the developing embryo or yolk-sac fry, however. No association could be demonstrated between the various thiamine hydrochloride treatment practices and hepatic cytochrome P450 dependent 7-ethoxyresorufin-O-deethylase (EROD) activity in the yolk-sac fry. An injection of thiamine hydrochloride into the peritoneal cavity of wild Baltic salmon females could be used to raise thiamine concentrations in their offspring in the rivers. The effect on smolt production in Finnish Baltic salmon rivers needs to be investigated further, however.

Familial pyrophosphate arthropathy. Occurrence and Crystal Identification.

PubMed

Bjelle, A

1981-01-01

Hereditary pyrophosphate arthropathy has been observed in three Swedish families and in a few other caucasian populations. The inheritance is most probably autosomal dominant with a variable penetrance. The most severe cases have been found in homozygotes among isolates of immigrants in Slovakia and Chile. Studies on genetic and etio-pathogenetic factors in hereditary pyrophosphate arthropathy, and the utilization of new diagnostic techniques for crystal identification, are important approaches towards a further understanding of the disease.

Controllable Fabrication of Amorphous Co-Ni Pyrophosphates for Tuning Electrochemical Performance in Supercapacitors.

PubMed

Chen, Chen; Zhang, Ning; He, Yulu; Liang, Bo; Ma, Renzhi; Liu, Xiaohe

2016-09-07

Incorporation of two transition metals offers an effective method to enhance the electrochemical performance in supercapacitors for transition metal compound based electrodes. However, such a configuration is seldom concerned in pyrophosphates. Here, amorphous phase Co-Ni pyrophosphates are fabricated as electrodes in supercapacitors. Through controllably adjusting the ratios of Co and Ni as well as the calcination temperature, the electrochemical performance can be tuned. An optimized amorphous Ni-Co pyrophosphate exhibits much higher specific capacitance than monometallic Ni and Co pyrophosphates and shows excellent cycling ability. When employing Ni-Co pyrophosphates as positive electrode and activated carbon as a negative electrode, the fabricated asymmetric supercapacitor cell exhibits favorable capacitance and cycling ability. This study provides facile methods to improve the transition metal pyrophosphate electrodes for efficient electrodes in electrochemical energy storage devices.

The PLUTO plastidial nucleobase transporter also transports the thiamin precursor hydroxymethylpyrimidine.

PubMed

Beaudoin, Guillaume A W; Johnson, Timothy S; Hanson, Andrew D

2018-04-27

In plants, the hydroxymethylpyrimidine (HMP) and thiazole precursors of thiamin are synthesized and coupled together to form thiamin in plastids. Mutants unable to form HMP can be rescued by exogenous HMP, implying the presence of HMP transporters in the plasma membrane and plastids. Analysis of bacterial genomes revealed a transporter gene that is chromosomally clustered with thiamin biosynthesis and salvage genes. Its closest Arabidopsis homolog, the plastidic nucleobase transporter (PLUTO), is co-expressed with several thiamin biosynthetic enzymes. Heterologous expression of PLUTO in Escherichia coli or Saccharomyces cerevisiae increased sensitivity to a toxic HMP analog, and disrupting PLUTO in an HMP-requiring Arabidopsis line reduced root growth at low HMP concentrations. These data implicate PLUTO in plastidial transport and salvage of HMP. © 2018 The Author(s).

The PLUTO plastidial nucleobase transporter also transports the thiamin precursor hydroxymethylpyrimidine

PubMed Central

Beaudoin, Guillaume A.W.; Johnson, Timothy S.; Hanson, Andrew D.

2018-01-01

In plants, the hydroxymethylpyrimidine (HMP) and thiazole precursors of thiamin are synthesized and coupled together to form thiamin in plastids. Mutants unable to form HMP can be rescued by exogenous HMP, implying the presence of HMP transporters in the plasma membrane and plastids. Analysis of bacterial genomes revealed a transporter gene that is chromosomally clustered with thiamin biosynthesis and salvage genes. Its closest Arabidopsis homolog, the plastidic nucleobase transporter (PLUTO), is co-expressed with several thiamin biosynthetic enzymes. Heterologous expression of PLUTO in Escherichia coli or Saccharomyces cerevisiae increased sensitivity to a toxic HMP analog, and disrupting PLUTO in an HMP-requiring Arabidopsis line reduced root growth at low HMP concentrations. These data implicate PLUTO in plastidial transport and salvage of HMP. PMID:29507060

Chloride permeability of rat brain membrane vesicles correlates with thiamine triphosphate content.

PubMed

Bettendorff, L; Hennuy, B; De Clerck, A; Wins, P

1994-07-25

Incubation of rat brain homogenates with thiamine or thiamine diphosphate (TDP) leads to a synthesis of thiamine triphosphate (TTP). In membrane vesicles subsequently prepared from the homogenates, increased TTP content correlates with increased 36Cl- uptake. A hyperbolic relationship was obtained with a K0.5 of 0.27 nmol TTP/mg protein. In crude mitochondrial fractions from the brains of animals previously treated with thiamine or sulbutiamine, a positive correlation between 36Cl- uptake and TTP content was found. These results, together with other results previously obtained with the patch-clamp technique, suggest that TTP is an activator of chloride channels having a large unit conductance.

Effects of detergents on the properties of 4-hydroxybenzoate. Polyprenyl transferase and the specificity of the polyprenyl pyrophosphate synthetic system in mitochondria.

PubMed

Nishino, T; Rudney, H

1977-02-22

The properties of 4-hydroxybenzoate:polyprenyl transferase and the system synthesizing polyprenyl pyrophosphate have been studied in mitochondria from rat and guinea pig livers. With solanesyl pyrophosphate and 4-hydroxybenzoate as substrates the formation of 3-nonaprenyl-4-hydroxybenzoate was linear with time, concentration of protein, and concentration of solanesyl pyrophosphate. Solanesyl monophosphate is inactive as a substrate and is noninhibitory. Conversion of solanesyl monophosphate to the pyrophosphate could not be detected. Detergents such as Triton X-100, Tween-80, and sodium deoxycholate activated the enzyme in mitochondria which were aged by freezing at -20 degrees C for periods ranging from 1 h to several days. Maximum activation also required Mg2+. In agreement with previous observation the effect of Mg2+ and Triton X-100 on fresh mitochondria was quite variable; however, activation with aged preparations was very consistent. Treatment with TritonX-100 causes al alteration in the biosynthetic pattern of rat liver mitochondria so that rather than nonaprenyl, decaprenyl, pyrophosphate is preferentially made in the presence of solanesyl pyrophosphate and isopentenyl pyrophosphate. In the presence of Triton X-100 and added pool of solanesyl pyrophosphate appears to exert a feedback inhibition on the incorporation of isopentenyl pyrophosphate into solanesyl pyrophosphate. In the case of guinea pig liver mitochondria a different pattern is observed with Triton X-100 in contrast to the rat. The de novo formation of decaprenyl pyrophosphate from isopentenyl pyrophosphate appears to be inhibited by Triton X-100, but the synthesis of decaprenyl pyrophosphate from isopentenyl pyrophosphate and nonaprenyl pyrophosphate is not inhibited. The data also indicate that in guinea pig liver in a system synthesizing decaprenyl pyrophosphate from isopentenyl pyrophosphate, there does not appear to be a detectable pool of nonaprenyl pyrophosphate. These results show that

Nonalcoholic Thiamine-Related Encephalopathy (Wernicke-Korsakoff Syndrome) Among Inpatients With Cancer: A Series of 18 Cases.

PubMed

Isenberg-Grzeda, Elie; Alici, Yesne; Hatzoglou, Vaios; Nelson, Christian; Breitbart, William

2016-01-01

Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine deficiency. Cancer predisposes to thiamine deficiency through various mechanisms. Although many case reports exist on nonalcoholic WKS in cancer, larger qualitative studies are lacking. Retrospective study of patients admitted to a cancer hospital and diagnosed with WKS during routine care on a psychiatric consultation service. Only patients with at least 1 additional supporting feature (magnetic resonance imaging findings, low serum thiamine concentrations, or response to treatment) were included. Data pertaining to demographics, risk factors, phenomenology, and outcomes were abstracted from medical records by chart review. In all, 18 patients were included. All patients developed WKS during cancer treatment. Hematologic malignancy, gastrointestinal tract tumors, low oral intake, and weight loss were common risk factors. All patients presented with cognitive dysfunction, most commonly impaired alertness, attention, and short-term memory. All were diagnosed by operational criteria proposed by Caine et al., 1997 (where 2 of the following are required: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment). Few exhibited Wernicke's classic triad. Diagnostic and treatment delay were common. Only 3 patients recovered fully. Nonalcoholic WKS can occur during cancer treatment and manifests clinically as delirium. Diagnosis should be made using operational criteria, not Wernicke's triad. Most patients were not underweight and had normal serum concentration of vitamin B12 and folate. A variety of mechanisms might predispose to thiamine deficiency and WKS in cancer. Given the high frequency of residual morbidity, studies should focus on decreasing diagnostic and treatment delay. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Nonalcoholic Thiamine-Related Encephalopathy (Wernicke-Korsakoff Syndrome) Among Inpatients With Cancer: A Series of 18 Cases

PubMed Central

Isenberg-Grzeda, Elie; Alici, Yesne; Hatzoglou, Vaios; Nelson, Christian; Breitbart, William

2016-01-01

Background Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine deficiency. Cancer predisposes to thiamine deficiency through various mechanisms. Although many case reports exist on nonalcoholic WKS in cancer, larger qualitative studies are lacking. Method Retrospective study of patients admitted to a cancer hospital and diagnosed with WKS during routine care on a psychiatric consultation service. Only patients with at least 1 additional supporting feature (magnetic resonance imaging findings, low serum thiamine concentrations, or response to treatment) were included. Data pertaining to demographics, risk factors, phenomenology, and outcomes were abstracted from medical records by chart review. Results In all, 18 patients were included. All patients developed WKS during cancer treatment. Hematologic malignancy, gastrointestinal tract tumors, low oral intake, and weight loss were common risk factors. All patients presented with cognitive dysfunction, most commonly impaired alertness, attention, and short-term memory. All were diagnosed by operational criteria proposed by Caine et al., 1997 (where 2 of the following are required: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment). Few exhibited Wernicke’s classic triad. Diagnostic and treatment delay were common. Only 3 patients recovered fully. Conclusion Nonalcoholic WKS can occur during cancer treatment and manifests clinically as delirium. Diagnosis should be made using operational criteria, not Wernicke’s triad. Most patients were not underweight and had normal serum concentration of vitamin B12 and folate. A variety of mechanisms might predispose to thiamine deficiency and WKS in cancer. Given the high frequency of residual morbidity, studies should focus on decreasing diagnostic and treatment delay. PMID:26791514

A Pyrophosphate Based Energy Generating Module

DTIC Science & Technology

2008-12-01

OMB control number. 1. REPORT DATE DEC 2008 2 . REPORT TYPE N/A 3 . DATES COVERED - 4. TITLE AND SUBTITLE A Pyrophosphate Based Energy...for each substrate (PPi, PEP, and AMP) using double reciprocal Lineweaver-Burk plots of saturation data. 10| 2 10| 3 10|4 10|5 10|6 10|7 10-11 10- 10...Partitioning 1 2 3 4 Bilayer - + + + α-Hemolysin - - + + Upper Reservoir +PPi, +PEP +PPi, +PEP +PPi, +PEP +PPi, +PEP, +Luc Lower Reservoir +AMP

Two inositol hexakisphosphate kinases drive inositol pyrophosphate synthesis in plants

USDA-ARS?s Scientific Manuscript database

Inositol pyrophosphates are novel cellular signaling molecules with newly discovered roles in energy sensing and metabolic control. Studies in eukaryotes have revealed that these compounds turn over rapidly, and thus only small amounts accumulate. Inositol pyrophosphates have not been the subject of...

Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

NASA Technical Reports Server (NTRS)

Kirilyuk, O. G.; Khmelevskiy, Y. V.

1980-01-01

By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

Perinatal Consumption of Thiamine-Fortified Fish Sauce in Rural Cambodia: A Randomized Clinical Trial.

PubMed

Whitfield, Kyly C; Karakochuk, Crystal D; Kroeun, Hou; Hampel, Daniela; Sokhoing, Ly; Chan, Benny B; Borath, Mam; Sophonneary, Prak; McLean, Judy; Talukder, Aminuzzaman; Lynd, Larry D; Li-Chan, Eunice C Y; Kitts, David D; Allen, Lindsay H; Green, Timothy J

2016-10-03

Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, remains a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine concentrations, placing breastfed infants at risk of beriberi. To determine if consumption of thiamine-fortified fish sauce yields higher erythrocyte thiamine diphosphate concentrations (eTDP) among lactating women and newborn infants and higher breast milk thiamine concentrations compared with a control sauce. In this double-blind randomized clinical trial, 90 pregnant women were recruited in the Prey Veng province, Cambodia. The study took place between October 2014 and April 2015. Women were randomized to 1 of 3 groups (n = 30) for ad libitum fish sauce consumption for 6 months: control (no thiamine), low-concentration (2 g/L), or high-concentration (8 g/L) fish sauce. Maternal eTDP was assessed at baseline (October 2014) and endline (April 2015). Secondary outcomes, breast milk thiamine concentration and infant eTDP, were measured at endline. Women's mean (SD) age and gestational stage were 26 (5) years and 23 (7) weeks, respectively. April 2015 eTDP was measured among 28 women (93%), 29 women (97%), and 23 women (77%) in the control, low-concentration, and high-concentration groups, respectively. In modified intent-to-treat analysis, mean baseline-adjusted endline eTDP was higher among women in the low-concentration (282nM; 95% CI, 235nM to 310nM) and high-concentration (254nM; 95% CI, 225nM to 284nM) groups compared with the control group (193nM; 95% CI, 164nM to 222M; P < .05); low-concentration and high-concentration groups did not differ (P = .19). Breast milk total thiamine concentrations were 14.4 μg/dL for the control group (95% CI, 12.3 μg/dL to 16.5 μg/dL) (to convert to nanomoles per liter, multiply by 29.6); 20.7 μg/dL for the low-concentration group (95% CI, 18.6 μg/dL to 22.7 μg/dL ); and 17

Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding

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

Wang, Huanchen; Falck, J.R.; Hall, Traci M. Tanaka

2012-01-11

Inositol pyrophosphates (such as IP7 and IP8) are multifunctional signaling molecules that regulate diverse cellular activities. Inositol pyrophosphates have 'high-energy' phosphoanhydride bonds, so their enzymatic synthesis requires that a substantial energy barrier to the transition state be overcome. Additionally, inositol pyrophosphate kinases can show stringent ligand specificity, despite the need to accommodate the steric bulk and intense electronegativity of nature's most concentrated three-dimensional array of phosphate groups. Here we examine how these catalytic challenges are met by describing the structure and reaction cycle of an inositol pyrophosphate kinase at the atomic level. We obtained crystal structures of the kinase domainmore » of human PPIP5K2 complexed with nucleotide cofactors and either substrates, product or a MgF{sub 3}{sup -} transition-state mimic. We describe the enzyme's conformational dynamics, its unprecedented topological presentation of nucleotide and inositol phosphate, and the charge balance that facilitates partly associative in-line phosphoryl transfer.« less

Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model

PubMed Central

Karuppagounder, Saravanan S.; Xu, Hui; Shi, Qingli; Chen, Lian H.; Pedrini, Steve; Pechman, David; Baker, Harriet; Beal, M. Flint; Gandy, Sam E.; Gibson, Gary E.

2009-01-01

Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased Aβ1–42 levels by about three-fold, β-CTF (C99) levels by 33% and β-secretase (BACE1) protein levels by 43%. TD induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Aβ and promotes accumulation of plaques independent of neuron loss or neuritic clusters. PMID:18406011

Organochlorine pesticides and thiamine in eggs of largemouth bass and American alligators and their relationship with early life-stage mortality

USGS Publications Warehouse

Sepulveda, M.S.; Wiebe, J.J.; Honeyfield, D.C.; Rauschenberger, H.R.; Hinterkopf, J.P.; Johnson, W.E.; Gross, T.S.

2004-01-01

Thiamine deficiency has been linked to early mortality syndrome in salmonids in the Great Lakes. This study was conducted to compare thiamine concentrations in American alligators (Alligator mississippiensis) and Florida largemouth bass (Micropterus salmoides floridanus) eggs from sites with high embryo mortality and high exposure to organochlorine pesticides (OCPs) (Lakes Apopka and Griffin, and Emeralda Marsh, Florida, USA) to those from sites that have historically exhibited low embryo mortality and low OCPs (Lakes Woodruff and Orange, Florida). During June-July 2000, 20 alligator clutches were collected from these sites, artificially incubated, and monitored for embryo mortality. Thiamine and OCPs were measured in one egg/clutch. During February 2002, 10 adult female bass were collected from Emeralda Marsh and Lake Woodruff and mature ovaries analyzed for thiamine and OCP concentrations. Although ovaries from the Emeralda Marsh bass contained almost 1,000-fold more OCPs compared with the reference site, Lake Woodruff, there were no differences in thiamine concentrations between sites (11,710 vs. 11,857 pmol/g). In contrast, alligator eggs from the reference site had five times the amount of thiamine compared with the contaminated sites (3,123 vs. 617 pmol/g). Similarly, clutches with > 55% hatch rates had significantly higher concentrations of thiamine compared with clutches with <54% hatch rates (1,119 vs. 201 pmol/g). These results suggest that thiamine deficiency might be playing an important role in alligator embryo survival but not in reproductive failure and recruitment of largemouth bass. The cause(s) of this thiamine deficiency are unknown but might be related to differences in the nutritional value of prey items across the sites studied and/or to the presence of high concentration of contaminants in eggs. ?? Wildlife Disease Association 2004.

Organochlorine pesticides and thiamine in eggs of largemouth bass and American alligators and their relationship with early life-stage mortality.

PubMed

Sepúlveda, Maria S; Wiebe, Jon J; Honeyfield, Dale C; Rauschenberger, Heath R; Hinterkopf, Joy P; Johnson, William E; Gross, Timothy S

2004-10-01

Thiamine deficiency has been linked to early mortality syndrome in salmonids in the Great Lakes. This study was conducted to compare thiamine concentrations in American alligators (Alligator mississippiensis) and Florida largemouth bass (Micropterus salmoides floridanus) eggs from sites with high embryo mortality and high exposure to organochlorine pesticides (OCPs) (Lakes Apopka and Griffin, and Emeralda Marsh, Florida, USA) to those from sites that have historically exhibited low embryo mortality and low OCPs (Lakes Woodruff and Orange, Florida). During June-July 2000, 20 alligator clutches were collected from these sites, artificially incubated, and monitored for embryo mortality. Thiamine and OCPs were measured in one egg/clutch. During February 2002, 10 adult female bass were collected from Emeralda Marsh and Lake Woodruff and mature ovaries analyzed for thiamine and OCP concentrations. Although ovaries from the Emeralda Marsh bass contained almost 1,000-fold more OCPs compared with the reference site, Lake Woodruff, there were no differences in thiamine concentrations between sites (11,710 vs. 11,857 pmol/g). In contrast, alligator eggs from the reference site had five times the amount of thiamine compared with the contaminated sites (3,123 vs. 617 pmol/g). Similarly, clutches with >55% hatch rates had significantly higher concentrations of thiamine compared with clutches with <54% hatch rates (1,119 vs. 201 pmol/g). These results suggest that thiamine deficiency might be playing an important role in alligator embryo survival but not in reproductive failure and recruitment of largemouth bass. The cause(s) of this thiamine deficiency are unknown but might be related to differences in the nutritional value of prey items across the sites studied and/or to the presence of high concentration of contaminants in eggs.

Prevention of delirium in trauma patients: Are we giving thiamine prophylaxis a fair chance?

PubMed Central

Blackmore, Christopher; Ouellet, Jean-Francois; Niven, Daniel; Kirkpatrick, Andrew W.; Ball, Chad G.

2014-01-01

Background Delirium is associated with increased morbidity and mortality in injured patients. Wernicke encephalopathy (WE) is delirium linked to malnutrition and chronic alcoholism. It is prevented with administration of thiamine. Our primary goal was to evaluate current blood alcohol level (BAL) testing and thiamine prophylaxis in severely injured patients. Methods We retrospectively reviewed the cases of 1000 consecutive severely injured patients admitted to hospital between Mar. 1, 2009, and Dec. 31, 2009. We used the patients’ medical records and the Alberta Trauma Registry. Results Among 1000 patients (mean age 48 yr, male sex 70%, mean injury severity score 23, mortality 10%), 627 underwent BAL testing at admission; 221 (35%) had a BAL greater than 0 mmol/L, and 189 (30%) had a BAL above the legal limit of 17.4 mmol/L. The mean positive BAL was 41.9 mmol/L. More than 4% had a known history of alcohol abuse. More patients were assaulted (20% v. 9%) or hit by motor vehicles (10% v. 6%) when intoxicated (both p < 0.05). Most injuries occurred after falls (37%) and motor vehicle collisions (33%). Overall, 17% of patients received thiamine prophylaxis. Of the 221 patients with elevated BAL, 44% received thiamine prophylaxis. Of those with a history of alcohol abuse, 77% received thiamine prophylaxis. Conclusion Despite the strong link between alcohol abuse, trauma and WE, more than one-third of patients were not screened for alcohol use. Furthermore, a minority of intoxicated patients received adequate prophylaxis against WE. Given the low risk and cost of BAL testing and thiamine prophylaxis and the high cost of delirium, standard protocols for prophylaxis are essential. PMID:24666443

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

PubMed Central

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E.

PubMed

Baumgartner, Matthias R

2013-01-01

The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis

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

Falk, R.H.; Lee, V.W.; Rubinow, A.

1983-03-01

To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (rmore » . 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.« less

Redirection of the Reaction Specificity of a Thermophilic Acetolactate Synthase toward Acetaldehyde Formation

PubMed Central

Cheng, Maria; Yoshiyasu, Hayato; Okano, Kenji; Ohtake, Hisao; Honda, Kohsuke

2016-01-01

Acetolactate synthase and pyruvate decarboxylase are thiamine pyrophosphate-dependent enzymes that convert pyruvate into acetolactate and acetaldehyde, respectively. Although the former are encoded in the genomes of many thermophiles and hyperthermophiles, the latter has been found only in mesophilic organisms. In this study, the reaction specificity of acetolactate synthase from Thermus thermophilus was redirected to catalyze acetaldehyde formation to develop a thermophilic pyruvate decarboxylase. Error-prone PCR and mutant library screening led to the identification of a quadruple mutant with 3.1-fold higher acetaldehyde-forming activity than the wild-type. Site-directed mutagenesis experiments revealed that the increased activity of the mutant was due to H474R amino acid substitution, which likely generated two new hydrogen bonds near the thiamine pyrophosphate-binding site. These hydrogen bonds might result in the better accessibility of H+ to the substrate-cofactor-enzyme intermediate and a shift in the reaction specificity of the enzyme. PMID:26731734

Delayed Influence of Spinal Cord Injury on the Amino Acids of NO• Metabolism in Rat Cerebral Cortex Is Attenuated by Thiamine

PubMed Central

Boyko, Alexandra; Ksenofontov, Alexander; Ryabov, Sergey; Baratova, Lyudmila; Graf, Anastasia; Bunik, Victoria

2018-01-01

Severe spinal cord injuries (SCIs) result in chronic neuroinflammation in the brain, associated with the development of cognitive and behavioral impairments. Nitric oxide (NO•) is a gaseous messenger involved in neuronal signaling and inflammation, contributing to nitrosative stress under dysregulated production of reactive nitrogen species. In this work, biochemical changes induced in the cerebral cortex of rats 8 weeks after SCI are assessed by quantification of the levels of amino acids participating in the NO• and glutathione metabolism. The contribution of the injury-induced neurodegeneration is revealed by comparison of the SCI- and laminectomy (LE)-subjected animals. Effects of the operative interventions are assessed by comparison of the operated (LE/SCI) and non-operated animals. Lower ratios of citrulline (Cit) to arginine (Arg) or Cit to ornithine and a more profound decrease in the ratio of lysine to glycine distinguish SCI animals from those after LE. The data suggest decreased NO• production from both Arg and homoarginine in the cortex 8 weeks after SCI. Both LE and SCI groups show a strong decrease in the level of cortex glutathione. The neurotropic, anti-inflammatory, and antioxidant actions of thiamine (vitamin B1) prompted us to study the thiamine effects on the SCI-induced changes in the NO• and glutathione metabolism. A thiamine injection (400 mg/kg intraperitoneally) within 24 h after SCI abrogates the changes in the cerebral cortex amino acids related to NO•. Thiamine-induced normalization of the brain glutathione levels after LE and SCI may involve increased supply of glutamate for glutathione biosynthesis. Thus, thiamine protects from sequelae of SCI on NO•-related amino acids and glutathione in cerebral cortex. PMID:29379782

Anthranilate phosphoribosyltransferase: Binding determinants for 5'-phospho-alpha-d-ribosyl-1'-pyrophosphate (PRPP) and the implications for inhibitor design.

PubMed

Evans, Genevieve L; Furkert, Daniel P; Abermil, Nacim; Kundu, Preeti; de Lange, Katrina M; Parker, Emily J; Brimble, Margaret A; Baker, Edward N; Lott, J Shaun

2018-02-01

Phosphoribosyltransferases (PRTs) bind 5'-phospho-α-d-ribosyl-1'-pyrophosphate (PRPP) and transfer its phosphoribosyl group (PRib) to specific nucleophiles. Anthranilate PRT (AnPRT) is a promiscuous PRT that can phosphoribosylate both anthranilate and alternative substrates, and is the only example of a type III PRT. Comparison of the PRPP binding mode in type I, II and III PRTs indicates that AnPRT does not bind PRPP, or nearby metals, in the same conformation as other PRTs. A structure with a stereoisomer of PRPP bound to AnPRT from Mycobacterium tuberculosis (Mtb) suggests a catalytic or post-catalytic state that links PRib movement to metal movement. Crystal structures of Mtb-AnPRT in complex with PRPP and with varying occupancies of the two metal binding sites, complemented by activity assay data, indicate that this type III PRT binds a single metal-coordinated species of PRPP, while an adjacent second metal site can be occupied due to a separate binding event. A series of compounds were synthesized that included a phosphonate group to probe PRPP binding site. Compounds containing a "bianthranilate"-like moiety are inhibitors with IC 50 values of 10-60μM, and K i values of 1.3-15μM. Structures of Mtb-AnPRT in complex with these compounds indicate that their phosphonate moieties are unable to mimic the binding modes of the PRib or pyrophosphate moieties of PRPP. The AnPRT structures presented herein indicated that PRPP binds a surface cleft and becomes enclosed due to re-positioning of two mobile loops. Copyright © 2017 Elsevier B.V. All rights reserved.

Taste and acceptance of pyrophosphates by rats and mice.

PubMed

McCaughey, Stuart A; Giza, Barbara K; Tordoff, Michael G

2007-06-01

The palatability and taste quality of pyrophosphates were evaluated in a series of behavioral and electrophysiological experiments. In two-bottle choice tests with water, rats strongly preferred some concentrations of Na3HP2O7 and Na4P2O7, moderately preferred some concentrations of K4P2O7 and Fe4(P2O7)3, and were indifferent to or avoided all concentrations of Ca2P2O7 and Na2H2P2O7. The contribution of sodium to the preference for sodium pyrophosphates was ascertained: 1) Rats with a choice between Na4P2O7 and NaCl preferred 1 mM Na4P2O7 to 4 mM NaCl but preferred 40 or 150 mM NaCl to 10 mM Na4P2O7, 2) blocking salt taste transduction by mixing Na4P2O7 with amiloride reduced preferences but did not eliminate them, and 3) three mouse strains (FVB/J, C57BL/6J, and CBA/J) known to differ in sodium preference had the same rank order of preferences for Na3HP2O7 and NaCl, but peak preferences were higher for Na3HP2O7 than for NaCl. The taste qualities of pyrophosphates were determined by measuring taste-evoked responses of neurons in the nucleus of the solitary tract of rats. Across-neuron patterns of activity for sodium pyrophosphates were similar to that of NaCl but the pattern of Na3HP2O7 plus amiloride was unique from those of sweet, salty, sour, bitter, and umami stimuli. Taken together, the results indicate that the high palatability of some concentrations of Na3HP2O7 and Na4P2O7 is due partially to their salty taste, but there must also be another cause, which may include a novel orosensory component distinct from the five major taste qualities.

Increasing thiamine concentrations in lake trout eggs from Lakes Huron and Michigan coincide with low alewife abundance

USGS Publications Warehouse

Riley, Stephen C.; Rinchard, Jacques; Honeyfield, Dale C.; Evans, Allison N.; Begnoche, Linda

2011-01-01

Lake trout Salvelinus namaycush in the Laurentian Great Lakes suffer from thiamine deficiency as a result of adult lake trout consuming prey containing thiaminase, a thiamine-degrading enzyme. Sufficiently low egg thiamine concentrations result in direct mortality of or sublethal effects on newly hatched lake trout fry. To determine the prevalence and severity of low thiamine in lake trout eggs, we monitored thiamine concentrations in lake trout eggs from 15 sites in Lakes Huron and Michigan from 2001 to 2009. Lake trout egg thiamine concentrations at most sites in both lakes were initially low and increased over time at 11 of 15 sites, and the proportion of females with egg thiamine concentrations lower than the recommended management objective of 4 nmol/g decreased over time at eight sites. Egg thiamine concentrations at five of six sites in Lakes Huron and Michigan were significantly inversely related to site-specific estimates of mean abundance of alewives Alosa pseudoharengus, and successful natural reproduction of lake trout has been observed in Lake Huron since the alewife population crashed. These results support the hypothesis that low egg thiamine in Great Lakes lake trout is associated with increased alewife abundance and that low alewife abundance may currently be a prerequisite for successful reproduction by lake trout in the Great Lakes.

The Long-Term Cost to the UK NHS and Social Services of Different Durations of IV Thiamine (Vitamin B1) for Chronic Alcohol Misusers with Symptoms of Wernicke's Encephalopathy Presenting at the Emergency Department.

PubMed

Wilson, Edward C F; Stanley, George; Mirza, Zulfiquar

2016-04-01

Wernicke's encephalopathy (WE) is an acute neuropsychiatric condition caused by depleted intracellular thiamine, most commonly arising in chronic alcohol misusers, who may present to emergency departments (EDs) for a variety of reasons. Guidelines recommend a minimum 5-day course of intravenous (IV) thiamine in at-risk patients unless WE can be excluded. To estimate the cost impact on the UK public sector (NHS and social services) of a 5-day course of IV thiamine, vs a 2- and 10-day course, in harmful or dependent drinkers presenting to EDs. A Markov chain model compared expected prognosis of patients under alternative admission strategies over 35 years. Model inputs were derived from a prospective cohort study, expert opinion via structured elicitation and NHS costing databases. Costs (2012/2013 price year) were discounted at 3.5 %. Increasing treatment from 2 to 5 days increased acute care costs but reduced the probability of disease progression and thus reduced the expected net costs by GBP87,000 per patient (95 % confidence interval GBP19,300 to GBP172,300) over 35 years. Increasing length of stay to optimize IV thiamine replacement will place additional strain on acute care but has potential UK public sector cost savings. Social services and the NHS should explore collaborations to realise both the health benefits to patients and savings to the public purse.

Development of thiamine deficiencies and early mortality syndrome in lake trout by feeding experimental and feral fish diets containing thiaminase

USGS Publications Warehouse

Honeyfield, D.C.; Hinterkopf, J.P.; Fitzsimons, J.D.; Tillitt, D.E.; Zajicek, J.L.; Brown, S.B.

2005-01-01

We conducted a laboratory investigation on the consequences of feeding predatory salmonids either experimental diets low in thiamine or diets containing alewife Alosa pseudoharengus. In experiment 1, adult lake trout Salvelinus namaycush were fed experimental diets containing bacterial thiaminase. In experiment 2, adult lake trout were fed natural prey species, alewives, and bloaters Coregonus hoyi. The diets consisted of four combinations of alewives and bloaters from Lake Michigan (100% alewives, 65% alewives–35% bloaters, 35% alewives–65% bloaters, and 100% bloaters), alewives from Cayuga Lake, a casein bacterial thiaminase, and a commercial trout diet. We assessed the effects of each diet on egg thiamine concentration and incidence of an embryonic early mortality syndrome (EMS). In experiment 1, incidence of EMS ranged from 0% to 100%. Significant relationships were found between the incidence of EMS and thiamine. In experiment 2, adult lake trout fed 100% alewives from either Lake Michigan or Cayuga Lake or fish fed the casein bacterial thiaminase diet produced eggs with low thiamine and swim-up fry with EMS. At either 35% or 65% alewives in the diet, egg thiamine was significantly lowered. The number of females that produced offspring that died from EMS were low but demonstrated the negative potential if feral lake trout foraged on either 35% or 65% alewives. Depleted egg thiamine and the onset of EMS required diets containing thiaminase for a minimum of 2 years in lake trout initially fully thiamine replete. We conclude that EMS can be caused by extensive feeding on 100% alewives and dietary levels of 35% or greater may prove detrimental to sustainable reproduction of salmonids in the Great Lakes. The data are consistent with that observed in feral lake trout, and it is concluded that EMS is the result of a thiamine deficiency.

Infant botulism: is there an association with thiamine deficiency?

PubMed

Ringe, Hannelore; Schuelke, Markus; Weber, Sven; Dorner, Brigitte G; Kirchner, Sebastian; Dorner, Martin B

2014-11-01

Infant botulism is an acute life-threatening condition and diagnosis is frequently delayed. Therefore, the best time window to administer specific antibodies, at present the only etiology-based therapy, is often missed, entailing long periods of hospitalization in the PICU. Here we present a 3-month-old boy with infant botulism and respiratory failure, who quickly and favorably responded to thiamine supplementation. From the feces we isolated Clostridium botulinum serotype A2. In addition to producing botulinum neurotoxin A, this strain carried the thiaminase I gene and produced thiaminase I. Accordingly, the child's feces were positive for thiaminase I activity. Because C botulinum group I strains are capable of producing thiaminase I, we speculate that thiamine degradation might further aggravate the paralytic symptoms caused by botulinum neurotoxins in infant botulism. Thus, supportive supplementation with thiamine could be beneficial to speed up recovery and to shorten hospitalization in some patients with infant botulism. Copyright © 2014 by the American Academy of Pediatrics.

Thiamine deficiency in childhood with attention to genetic causes: Survival and outcome predictors.

PubMed

Ortigoza-Escobar, Juan Darío; Alfadhel, Majid; Molero-Luis, Marta; Darin, Niklas; Spiegel, Ronen; de Coo, Irenaeus F; Gerards, Mike; Taylor, Robert W; Artuch, Rafael; Nashabat, Marwan; Rodríguez-Pombo, Pilar; Tabarki, Brahim; Pérez-Dueñas, Belén

2017-09-01

Primary and secondary conditions leading to thiamine deficiency have overlapping features in children, presenting with acute episodes of encephalopathy, bilateral symmetric brain lesions, and high excretion of organic acids that are specific of thiamine-dependent mitochondrial enzymes, mainly lactate, alpha-ketoglutarate, and branched chain keto-acids. Undiagnosed and untreated thiamine deficiencies are often fatal or lead to severe sequelae. Herein, we describe the clinical and genetic characterization of 79 patients with inherited thiamine defects causing encephalopathy in childhood, identifying outcome predictors in patients with pathogenic SLC19A3 variants, the most common genetic etiology. We propose diagnostic criteria that will aid clinicians to establish a faster and accurate diagnosis so that early vitamin supplementation is considered. Ann Neurol 2017;82:317-330. © 2017 American Neurological Association.

Gizzard shad thiaminase activity and its effect on the thiamine status of captive American alligators Alligator mississippiensis.

PubMed

Ross, J Perran; Honeyfield, Dale C; Brown, Scott B; Brown, Lisa R; Waddle, Amanda Rice; Welker, Michael E; Schoeb, Trenton R

2009-12-01

Adult mortality and low egg hatch rate were observed among American alligators Alligator mississippiensis in Lake Griffin, Florida, between 1998 and 2003. Previous studies show that the alligator mortality is due to neurological impairment associated with thiamine (vitamin Bt) deficiency. This study determined the rate of thiaminase activity in gizzard shad Dorosoma cepedianum, a fish often eaten by alligators, and examined the thiamine status of captive adult alligators fed only gizzard shad. We found that the thiaminase activity of gizzard shad in Lake Griffin is 16,409 +/- 2,121 pmol/g/min (mean +/- 2SEs). This high rate of thiaminase activity was present in most months and across a wide range of shad sizes. Seven alligators were captured in the wild from Lake Griffin and Lake Woodruff, held in captivity, and fed gizzard shad. We monitored blood and muscle thiamine levels throughout the experiment and liver thiamine at the end. Over a period of 6-12 months, all of the alligators maintained weight but blood and muscle thiamine levels decreased to 25-50% of the original (healthy) values. Three animals with the greatest reduction in thiamine died, demonstrating mobility impairment and neural histopathology similar to those seen in wild alligators in Lake Griffin. Two alligators were fed shad for 10 months but then treated with thiamine. These animals showed a reduction in thiamine while eating shad, but treatment restored their thiamine levels to the initial values, which were comparable to those of normal wild Lake Griffin alligators. We demonstrated that thiamine deficiency can be induced by a diet of gizzard shad and cause neurological signs and death in alligators in captivity. We conclude that the thiaminase activity in gizzard shad is high enough to cause thiamine deficiency in wild alligators when shad are a major part of their diet.

Effect of added thiamine on the key odorant compounds and aroma of cooked ham.

PubMed

Thomas, Caroline; Mercier, Frédéric; Tournayre, Pascal; Martin, Jean-Luc; Berdagué, Jean-Louis

2015-04-15

This study shows that thiamine plays a major role in the formation of three key odorants of cooked ham: 2-methyl-3-furanthiol, 2-methyl-3-methyldithiofuran, and bis(2-methyl-3-furyl)disulphide. Analyses revealed that under identical cooking conditions, the productions of these three aroma compounds increase in a closely intercorrelated way when the dose of thiamine increases. Using a specific 2-methyl-3-furanthiol extraction-quantification method, it was possible to relate the amounts of thiamine added in model cooked hams to the amounts of 2-methyl-3-furanthiol produced in the cooking process. Sensory analyses highlighted the role of thiamine as a precursor of cooked ham aroma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamic Changes in Yeast Phosphatase Families Allow for Specialization in Phosphate and Thiamine Starvation.

PubMed

Nahas, John V; Iosue, Christine L; Shaik, Noor F; Selhorst, Kathleen; He, Bin Z; Wykoff, Dennis D

2018-05-10

Convergent evolution is often due to selective pressures generating a similar phenotype. We observe relatively recent duplications in a spectrum of Saccharomycetaceae yeast species resulting in multiple phosphatases that are regulated by different nutrient conditions - thiamine and phosphate starvation. This specialization is both transcriptional and at the level of phosphatase substrate specificity. In Candida glabrata , loss of the ancestral phosphatase family was compensated by the co-option of a different histidine phosphatase family with three paralogs. Using RNA-seq and functional assays, we identify one of these paralogs, CgPMU3 , as a thiamine phosphatase. We further determine that the 81% identical paralog CgPMU2 does not encode thiamine phosphatase activity; however, both are capable of cleaving the phosphatase substrate, 1-napthyl-phosphate. We functionally demonstrate that members of this family evolved novel enzymatic functions for phosphate and thiamine starvation, and are regulated transcriptionally by either nutrient condition, and observe similar trends in other yeast species. This independent, parallel evolution involving two different families of histidine phosphatases suggests that there were likely similar selective pressures on multiple yeast species to recycle thiamine and phosphate. In this work, we focused on duplication and specialization, but there is also repeated loss of phosphatases, indicating that the expansion and contraction of the phosphatase family is dynamic in many Ascomycetes. The dynamic evolution of the phosphatase gene families is perhaps just one example of how gene duplication, co-option, and transcriptional and functional specialization together allow species to adapt to their environment with existing genetic resources. Copyright © 2018, G3: Genes, Genomes, Genetics.

Thiamine primed defense provides reliable alternative to systemic fungicide carbendazim against sheath blight disease in rice (Oryza sativa L.).

PubMed

Bahuguna, Rajeev Nayan; Joshi, Rohit; Shukla, Alok; Pandey, Mayank; Kumar, J

2012-08-01

A novel pathogen defense strategy by thiamine priming was evaluated for its efficacy against sheath blight pathogen, Rhizoctonia solani AG-1A, of rice and compared with that of systemic fungicide, carbendazim (BCM). Seeds of semidwarf, high yielding, basmati rice variety Vasumati were treated with thiamine (50 mM) and BCM (4 mM). The pot cultured plants were challenge inoculated with R. solani after 40 days of sowing and effect of thiamine and BCM on rice growth and yield traits was examined. Higher hydrogen peroxide content, total phenolics accumulation, phenylalanine ammonia lyase (PAL) activity and superoxide dismutase (SOD) activity under thiamine treatment displayed elevated level of systemic resistance, which was further augmented under challenging pathogen infection. High transcript level of phenylalanine ammonia lyase (PAL) and manganese superoxide dismutase (MnSOD) validated mode of thiamine primed defense. Though minimum disease severity was observed under BCM treatment, thiamine produced comparable results, with 18.12 per cent lower efficacy. Along with fortifying defense components and minor influence on photosynthetic pigments and nitrate reductase (NR) activity, thiamine treatment significantly reduced pathogen-induced loss in photosynthesis, stomatal conductance, chlorophyll fluorescence, NR activity and NR transcript level. Physiological traits affected under pathogen infection were found signatory for characterizing plant's response under disease and were detectable at early stage of infection. These findings provide a novel paradigm for developing alternative, environmentally safe strategies to control plant diseases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Thiamine deficiency in Cambodian infants with and without beriberi.

PubMed

Coats, Debra; Shelton-Dodge, Kelsey; Ou, Kevanna; Khun, Vannara; Seab, Sommon; Sok, Kimsan; Prou, Chiva; Tortorelli, Silvia; Moyer, Thomas P; Cooper, Lisa E; Begley, Tadhg P; Enders, Felicity; Fischer, Philip R; Topazian, Mark

2012-11-01

To test the hypothesis that heavy metal toxicity and consumption of thiaminase-containing foods predispose to symptomatic thiamine deficiency. In a case-control study, thiamine diphosphate (TDP) blood concentrations were measured in 27 infants diagnosed with beriberi at a rural clinic, as well as their mothers and healthy Cambodian and American controls. Blood and urine levels of lead, arsenic, cadmium, mercury, and thallium were measured. Local food samples were analyzed for thiaminase activity. Mean TDP level among cases and Cambodian controls was 48 and 56 nmol/L, respectively (P = .08) and was 132 nmol/L in American controls (P < .0001 compared with both Cambodian groups). Mean TDP level of mothers of cases and Cambodian controls was 57 and 57 nmol/L (P = .92), and was 126 nmol/L in American mothers (P < .0001 compared with both Cambodian groups). Cases (but not controls) had lower blood TDP levels than their mothers (P = .02). Infant TDP level decreased with infant age and was positively associated with maternal TDP level. Specific diagnostic criteria for beriberi did not correlate with TDP level. There was no correlation between heavy metal levels and either TDP level or case/control status. No thiaminase activity was observed in food samples. Thiamine deficiency is endemic among infants and nursing mothers in rural southeastern Cambodia and is often clinically inapparent. Neither heavy metal toxicity nor consumption of thiaminase-containing foods account for thiamine deficiency in this region. Copyright © 2012 Mosby, Inc. All rights reserved.

Preventing the Wernicke-Korsakoff syndrome in Australia: cost-effectiveness of thiamin-supplementation alternatives.

PubMed

Connelly, L; Price, J

1996-04-01

Alcoholic Wernicke's encephalopathy has been commonplace in Australia for many years and, as this syndrome is attributed to a deficiency in the diet, it should be preventable. This study employs conventional cost-effectiveness methodology to compare the economic efficiency of several thiamin-supplementation alternatives that have been proposed for the prevention of Wernicke's encephalopathy. A series of rankings of these measures is derived from an estimated cost per case averted for each of the alternatives studied. These rankings identify the least cost-effective thiamin-supplementation alternative as that of enriching bread-making flour with thiamin.

Intravenous thiamine is associated with increased oxygen consumption in critically ill patients with preserved cardiac index.

PubMed

Berg, Katherine M; Gautam, Shiva; Salciccioli, Justin D; Giberson, Tyler; Saindon, Brian; Donnino, Michael W

2014-12-01

Oxygen consumption may be impaired in critically ill patients. To evaluate the effect of intravenous thiamine on oxygen consumption ([Formula: see text]o2) in critically ill patients. This was a small, exploratory open-label pilot study conducted in the intensive care units at a tertiary care medical center. Critically ill adults requiring mechanical ventilation were screened for enrollment. Oxygen consumption ([Formula: see text]o2) and cardiac index (CI) were recorded continuously for 9 hours. After 3 hours of baseline data collection, 200 mg of intravenous thiamine was administered. The outcome was change in [Formula: see text]o2 after thiamine administration. Twenty patients were enrolled and 3 were excluded because of incomplete [Formula: see text]o2 data, leaving 17 patients for analysis. There was a trend toward increase in [Formula: see text]o2 after thiamine administration (16.3 ml/min, SE 8.5; P = 0.052). After preplanned adjustment for changes in CI in case of a delivery-dependent state in some patients (with exclusion of one additional patient because of missing CI data), this became statistically significant (16.9 ml/min, SE 8.6; P = 0.047). In patients with average CI greater than our cohort's mean value of 3 L/min/m(2), [Formula: see text]o2 increased by 70.9 ml/min (±16; P < 0.0001) after thiamine. Thiamine had no effect in patients with reduced CI (< 2.4 L/min/m(2)). There was no association between initial thiamine level and change in [Formula: see text]o2 after thiamine administration. The administration of a single dose of thiamine was associated with a trend toward increase in [Formula: see text]o2 in critically ill patients. There was a significant increase in [Formula: see text]o2 in those patients with preserved or elevated CI. Further study is needed to better characterize the role of thiamine in oxygen extraction. Clinical trial registered with www.clinicaltrials.gov (NCT01462279).

Reappearance of beriberi heart disease in Japan. A study of 23 cases.

PubMed

Kawai, C; Wakabayashi, A; Matsumura, T; Yui, Y

1980-09-01

Twenty-three Japanese patients with beriberi heart disease, 17 of them teenagers, were studied. The recent tendency for teenagers to take excessive sweet carbonated soft drinks, instant noodles and powermill-polished rice readily induces relative thiamine deficiency. A sudden increase in thiamine requirements due to strenuous exercise can result in overt beriberi heart disease. Alcohol had nothing to do with the development of the disease. Characteristic features commonly seen in teenage patients include peripheral edema, low peripheral vascular resistance, increased venous pressure enlarged heart, T wave abnormalities, hyperkinetic circulatory state and increased circulating blood volume. Thiamine deficiency was confirmed by a decrease in blood thiamine concentration, a decrease in erythrocyte transketolase activity and an increase in thiamine pyrophosphate (TPP) effect. Improvement was rapidly achieved with thiamine administration, balanced nutrition and rest, especially in the teenage patients. Increased circulating blood volume was useful in differentiating beriberi heart disease from hyperthyroidism.

Genotype and environment effects on the contents of vitamins B1, B2, B3, and B6 in wheat grain.

PubMed

Shewry, Peter R; Van Schaik, Frank; Ravel, Catherine; Charmet, Gilles; Rakszegi, Mariann; Bedo, Zoltan; Ward, Jane L

2011-10-12

The total contents of thiamine (vitamin B1), riboflavin (B2), and pyridoxine (B6) and the bioavailable forms of niacin (B3) were determined on wholemeal flours of 24 winter wheat varieties grown on four sites (United Kingdom, Poland, France, and Hungary) in 2007 and of two spring varieties grown on the same sites with the exception of Poland. The contents of vitamins B1 (5.53-13.55 μg/g dw), B2 (0.77-1.40 μg/g dw), and B6 (1.27-2.97 μg/g dw) were within the ranges reported previously, while the content of bioavailable vitamin B3 (0.16-1.74 μg/g dw) was about 10-15% of the total contents of vitamin B3 reported in previous studies. Strong correlations were observed between the contents of vitamins B1, B3, and B6, and partitioning of the variance in the contents of these three B vitamins showed that between 48 and 70% was accounted for by the environment. By contrast, the content of vitamin B2 was not correlated with the contents of other B vitamins, and 73% of the variance was ascribed to the error term, which suggests that this trait may be influenced by genotype × environment interactions. Whereas the contents of vitamins B1, B3, and B6 were correlated positively with the mean temperature from heading to harvest (r > 0.8), the content of vitamin B2 was positively correlated with precipitation during the 3 months prior to heading. These results are discussed in relation to the development of new wheat varieties with enhanced health benefits.

Aminoimidazole Carboxamide Ribotide Exerts Opposing Effects on Thiamine Synthesis in Salmonella enterica

PubMed Central

Bazurto, Jannell V.; Heitman, Nicholas J.

2015-01-01

ABSTRACT In Salmonella enterica, the thiamine biosynthetic intermediate 5-aminoimidazole ribotide (AIR) can be synthesized de novo independently of the early purine biosynthetic reactions. This secondary route to AIR synthesis is dependent on (i) 5-amino-4-imidazolecarboxamide ribotide (AICAR) accumulation, (ii) a functional phosphoribosylaminoimidazole-succinocarboxamide (SAICAR) synthetase (PurC; EC 6.3.2.6), and (iii) methionine and lysine in the growth medium. Studies presented here show that AICAR is a direct precursor to AIR in vivo. PurC-dependent conversion of AICAR to AIR was recreated in vitro. Physiological studies showed that exogenous nutrients (e.g., methionine and lysine) antagonize the inhibitory effects of AICAR on the ThiC reaction and decreased the cellular thiamine requirement. Finally, genetic results identified multiple loci that impacted the effect of AICAR on thiamine synthesis and implicated cellular aspartate levels in AICAR-dependent AIR synthesis. Together, the data here clarify the mechanism that allows conditional growth of a strain lacking the first five biosynthetic enzymes, and they provide additional insights into the complexity of the metabolic network and its plasticity. IMPORTANCE In bacteria, the pyrimidine moiety of thiamine is derived from aminoimidazole ribotide (AIR), an intermediate in purine biosynthesis. A previous study described conditions under which AIR synthesis is independent of purine biosynthesis. This work is an extension of that previous study and describes a new synthetic pathway to thiamine that depends on a novel thiamine precursor and a secondary activity of the biosynthetic enzyme PurC. These findings provide mechanistic details of redundancy in the synthesis of a metabolite that is essential for nucleotide and coenzyme biosynthesis. Metabolic modifications that allow the new pathway to function or enhance it are also described. PMID:26100042

Simultaneous Determination of Total Vitamins B1, B2, B3, and B6 in Infant Formula and Related Nutritionals by Enzymatic Digestion and LC-MS/MS: Single-Laboratory Validation, First Action 2015.14.

PubMed

Salvati, Louis M; McClure, Sean C; Reddy, Todime M; Cellar, Nicholas A

2016-05-01

This method provides simultaneous determination of total vitamins B1, B2, B3, and B6 in infant formula and related nutritionals (adult and infant). The method was given First Action for vitamins B1, B2, and B6, but not B3, during the AOAC Annual Meeting in September 2015. The method uses acid phosphatase to dephosphorylate the phosphorylated vitamin forms. It then measures thiamine (vitamin B1); riboflavin (vitamin B2); nicotinamide and nicotinic acid (vitamin B3); and pyridoxine, pyridoxal, and pyridoxamine (vitamin B6) from digested sample extract by liquid chromatography-tandem mass spectrometry. A single-laboratory validation was performed on 14 matrixes provided by the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) to demonstrate method effectiveness. The method met requirements of the AOAC SPIFAN Standard Method Performance Requirement for each of the three vitamins, including average over-spike recovery of 99.6 ± 3.5%, average repeatability of 1.5 ± 0.8% relative standard deviation, and average intermediate precision of 3.9 ± 1.3% relative standard deviation.

Thiamine content of eggs and lengths of coho salmon (Oncorhynchus kisutch) in relation to abundance of alewife (Alosa pseudoharengus) in eastern Lake ontario, 2003 to 2006

USGS Publications Warehouse

Ketola, H.G.; Rinchard, J.; O'Gorman, R.; Begnoche, L.J.; Bishop, D.L.; Greulich, A.W.

2009-01-01

Early mortality syndrome in fry of Great Lakes salmonines is linked to reduced levels of thiamine in eggs, which reflects maternal consumption of forage fishes such as alewife (Alosa pseudoharengus) that contain thiaminase, an enzyme that destroys thiamine. We assessed annual variations in abundance and condition of alewives and thiamine status of coho salmon (Oncorhynchus kisutch) in Lake Ontario. We analyzed total thiamine in eggs of 20 coho salmon collected annually between 2003 and 2006 at the Salmon River Hatchery on the Salmon River, New York. Alewife abundance was assessed annually in southern and eastern Lake Ontario with bottom trawls during late April and early May. Mean thiamine concentration in eggs varied annually, with those collected in 2003 (2.5 nmol/g) being significantly higher than those collected in 2004 to 2006 (1.5 to 1.7 nmol/g). Although we did not test survival of fry, if reported threshold levels of thiamine for preventing mortality of Lake Michigan coho salmon fry apply, then many or most Lake Ontario coho salmon produced fry were likely to incur thiamine-deficiency mortality, especially during years 2004 to 2006. Comparison to indices of annual abundance of alewife in Lake Ontario with thiamine concentration in coho salmon eggs failed to show any significant correlations (P > 0.05). However, total length of female spawning coho salmon was positively correlated (P < 0.05) with increasing condition and estimated energy content of adult alewives in the previous spring. These results suggest that growth of coho salmon in Lake Ontario was first limited by energy intake, whereas the amount of thiamine provided by alewives was sufficient for growth (in length) but not for producing thiamine-adequate eggs.

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5878 - Thiamine mononitrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Thiamine mononitrate. 582.5878 Section 582.5878 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5878 - Thiamine mononitrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiamine mononitrate. 582.5878 Section 582.5878 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

[Nutritional value of daily diets prepared in several regions of the country. Part V. Value of group b vitamins].

PubMed

Nadolna, I; Wiśniewska, W; Kunachowicz, H

1991-01-01

Studies of the content of group B vitamins: thiamin, riboflavin, niacin and vitamin b6 in daily diets of manual and mental workers with medium income were carried on. The diets were prepared for five regions of the country (Warszawa, Lublin, Olsztyn, Poznań, Wrocław) under laboratory conditions. These diets contained respectively: thiamin 1.17 and 1.11 mg, riboflavin 1.48 and 1.55 mg; niacin 11.3 and 10.2 mg and vitamin B6 1.50 and 1.21 mg per day. According to the studies the realization of daily requirements by these diets for thiamin were met 82 and 98%, for niacin 62 and 65%, and for vitamin B6 79 and 64%. The comparison of the presently studied diets with the ones from 1973, 1980 and 1981 showed that the content of niacin and vitamin B6 intakes systematically decrease. There were no considerable differences in the contents of group B vitamins between diets prepared in all five regions of Poland.

Enhanced triterpene accumulation in Panax ginseng hairy roots overexpressing mevalonate-5-pyrophosphate decarboxylase and farnesyl pyrophosphate synthase.

PubMed

Kim, Yong-Kyoung; Kim, Yeon Bok; Uddin, Md Romij; Lee, Sanghyun; Kim, Soo-Un; Park, Sang Un

2014-10-17

To elucidate the function of mevalonate-5-pyrophosphate decarboxylase (MVD) and farnesyl pyrophosphate synthase (FPS) in triterpene biosynthesis, the genes governing the expression of these enzymes were transformed into Panax ginseng hairy roots. All the transgenic lines showed higher expression levels of PgMVD and PgFPS than that by the wild-type control. Among the hairy root lines transformed with PgMVD, M18 showed the highest level of transcription compared to the control (14.5-fold higher). Transcriptions of F11 and F20 transformed with PgFPS showed 11.1-fold higher level compared with control. In triterpene analysis, M25 of PgMVD produced 4.4-fold higher stigmasterol content (138.95 μg/100 mg, dry weight [DW]) than that by the control; F17 of PgFPS showed the highest total ginsenoside (36.42 mg/g DW) content, which was 2.4-fold higher compared with control. Our results indicate that metabolic engineering in P. ginseng was successfully achieved through Agrobacterium rhizogenes-mediated transformation and that the accumulation of phytosterols and ginsenosides was enhanced by introducing the PgMVD and PgFPS genes into the hairy roots of the plant. Our results suggest that PgMVD and PgFPS play an important role in the triterpene biosynthesis of P. ginseng.

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium...

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium...

Thiamin biosynthesis in Saccharomyces cerevisiae. Origin of carbon-2 of the thiazole moiety.

PubMed Central

White, R L; Spenser, I D

1979-01-01

Radioactivity from [2-14C]glycine enters C-2 of the thiazole moiety of thiamin and no other site, in Saccharomyces cerevisiae (strains A.T.C.C. 24903 and 39916, H.J. Bunker). Radioactivity from L-[Me-14C]methionine or from DL-[2-14C]tyrosine does not enter thiamin. PMID:384994

A pyrophosphate-responsive gadolinium(III) MRI contrast agent.

PubMed

Surman, Andrew J; Bonnet, Célia S; Lowe, Mark P; Kenny, Gavin D; Bell, Jimmy D; Tóth, Eva; Vilar, Ramon

2011-01-03

This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd(3+) and Eu(3+) , DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln(3+) /anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide "arms" of these ligands, and the interaction of the resulting Gd-Zn(2) complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5'-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H(2) O and D(2) O, (17) O and (31) P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of a Clostridium botulinum C143S thiaminase I/thiamin complex reveals active site architecture .

PubMed

Sikowitz, Megan D; Shome, Brateen; Zhang, Yang; Begley, Tadhg P; Ealick, Steven E

2013-11-05

Thiaminases are responsible for the degradation of thiamin and its metabolites. Two classes of thiaminases have been identified based on their three-dimensional structures and their requirements for a nucleophilic second substrate. Although the reactions of several thiaminases have been characterized, the physiological role of thiamin degradation is not fully understood. We have determined the three-dimensional X-ray structure of an inactive C143S mutant of Clostridium botulinum (Cb) thiaminase I with bound thiamin at 2.2 Å resolution. The C143S/thiamin complex provides atomic level details of the orientation of thiamin upon binding to Cb-thiaminase I and the identity of active site residues involved in substrate binding and catalysis. The specific roles of active site residues were probed by using site directed mutagenesis and kinetic analyses, leading to a detailed mechanism for Cb-thiaminase I. The structure of Cb-thiaminase I is also compared to the functionally similar but structurally distinct thiaminase II.

Complete recovery from undertreated Wernicke-Korsakoff syndrome following aggressive thiamine treatment.

PubMed

Paparrigopoulos, Thomas; Tzavellas, Elias; Karaiskos, Dimitris; Kouzoupis, Anastasios; Liappas, Ioannis

2010-01-01

Wernicke-Korsakoff syndrome (WKS) is a neuropsychiatric condition which results from thiamine deficiency, most commonly due to alcohol abuse. The prognosis of WKS is poor and its outcome depends mainly on prompt treatment. A 52-year-old male with a ten-year history of heavy alcohol abuse was admitted in hospital and treated for WKS. Ataxic and oculomotor symptoms promptly reversed following standard treatment but no change was observed in higher mental functioning. Although the protracted WK symptoms made the patient's improvement unlikely, aggressive treatment with thiamine (600 mg/day orally and 300 mg/day intramuscularly) fully reversed the condition within two months. Even though prolongation of undertreatment of WKS typically precludes significant improvement of symptoms due to irreversible damage of the brain, at least in some cases, higher thiamine doses (over 500 mg/day) for a longer period (at least three months) than usually recommended should be tried.

A Novel Inositol Pyrophosphate Phosphatase in Saccharomyces cerevisiae: Siw14 PROTEIN SELECTIVELY CLEAVES THE β-PHOSPHATE FROM 5-DIPHOSPHOINOSITOL PENTAKISPHOSPHATE (5PP-IP5).

PubMed

Steidle, Elizabeth A; Chong, Lucy S; Wu, Mingxuan; Crooke, Elliott; Fiedler, Dorothea; Resnick, Adam C; Rolfes, Ronda J

2016-03-25

Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, and can mediate protein phosphorylation. Although the inositol kinases underlying inositol pyrophosphate biosynthesis are well characterized, the phosphatases that selectively regulate their cellular pools are not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of the Nudix protein family have been demonstrated to dephosphorylate inositol pyrophosphates; however, theSaccharomyces cerevisiaehomolog Ddp1 prefers inorganic polyphosphate over inositol pyrophosphates. We identified a novel phosphatase of the recently discovered atypical dual specificity phosphatase family as a physiological inositol pyrophosphate phosphatase. Purified recombinant Siw14 hydrolyzes the β-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5or IP7)in vitro. In vivo,siw14Δ yeast mutants possess increased IP7levels, whereas heterologousSIW14overexpression eliminates IP7from cells. IP7levels increased proportionately whensiw14Δ was combined withddp1Δ orvip1Δ, indicating independent activity by the enzymes encoded by these genes. We conclude that Siw14 is a physiological phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7isoform 5PP-IP5to IP6. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Bioactive calcium pyrophosphate glasses and glass-ceramics.

PubMed

Kasuga, Toshihiro

2005-01-01

Calcium phosphate glass-based materials in the pyrophosphate region are briefly reviewed. Calcium pyrophosphate glasses can be prepared by including a small amount of TiO(2) (

Energy and glucose pathways in thiamine deficient primary rat brain microvascular endothelial cells.

PubMed

Ham, D; Karska-Wysocki, B

2005-12-01

Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

Structural determinants of enzyme binding affinity: the E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate.

PubMed

Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Sax, Martin; Brunskill, Andrew; Nemeria, Natalia; Jordan, Frank; Furey, William

2004-03-09

Thiamin thiazolone diphosphate (ThTDP), a potent inhibitor of the E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), binds to the enzyme with greater affinity than does the cofactor thiamin diphosphate (ThDP). To identify what determines this difference, the crystal structure of the apo PDHc E1 component complex with ThTDP and Mg(2+) has been determined at 2.1 A and compared to the known structure of the native holoenzyme, PDHc E1-ThDP-Mg(2+) complex. When ThTDP replaces ThDP, reorganization occurs in the protein structure in the vicinity of the active site involving positional and conformational changes in some amino acid residues, a change in the V coenzyme conformation, addition of new hydration sites, and elimination of others. These changes culminate in an increase in the number of hydrogen bonds to the protein, explaining the greater affinity of the apoenzyme for ThTDP. The observed hydrogen bonding pattern is not an invariant feature of ThDP-dependent enzymes but rather specific to this enzyme since the extra hydrogen bonds are made with nonconserved residues. Accordingly, these sequence-related hydrogen bonding differences likewise explain the wide variation in the affinities of different thiamin-dependent enzymes for ThTDP and ThDP. The sequence of each enzyme determines its ability to form hydrogen bonds to the inhibitor or cofactor. Mechanistic roles are suggested for the aforementioned reorganization and its reversal in PDHc E1 catalysis: to promote substrate binding and product release. This study also provides additional insight into the role of water in enzyme inhibition and catalysis.

Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol.

PubMed

Day, Ed; Bentham, Peter W; Callaghan, Rhiannon; Kuruvilla, Tarun; George, Sanju

2013-07-01

Autopsy studies suggest that Wernicke-Korsakoff syndrome (WKS) is not a rare disorder, particularly in individuals who abuse alcohol. Thiamine has been established as the treatment of choice for over 50 years, but uncertainty remains about appropriate dosage and duration. Current practice guidelines are based on case reports and clinical experience. This is an update of a review first published in 2004 and last updated in 2008. • To assess the efficacy of thiamine in preventing and treating the manifestations of WKS due to excess alcohol consumption. • To determine the optimum form, dose and duration of thiamine treatment for this indication. ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 6 September 2012 using the term thiamine OR aneurine. ALOIS contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trial databases and grey literature sources. Any randomised trials comparing thiamine with alternative interventions or comparing different thiamine regimens (varying in formulation, dose or duration of administration). All abstracts were independently inspected by two reviewers (ED and PWB), and relevant articles were retrieved and assessed for methodological quality using criteria provided in the Cochrane Handbook for Systematic Reviews of Interventions. Two studies were identified that met the inclusion criteria, but only one contained sufficient data for quantitative analysis. Ambrose (2001) randomly assigned participants (n = 107) to one of five doses of intramuscular thiamine and measured outcomes after 2 days of treatment. We compared the lowest dose (5 mg/day) with each of the other four doses. A significant difference favoured 200 mg/day compared with the 5-mg/day dose in determining the number of trials needed to meet inclusion criteria

Spectrophotometric determination of ternary mixtures of thiamin, riboflavin and pyridoxal in pharmaceutical and human plasma by least-squares support vector machines.

PubMed

Niazi, Ali; Zolgharnein, Javad; Afiuni-Zadeh, Somaie

2007-11-01

Ternary mixtures of thiamin, riboflavin and pyridoxal have been simultaneously determined in synthetic and real samples by applications of spectrophotometric and least-squares support vector machines. The calibration graphs were linear in the ranges of 1.0 - 20.0, 1.0 - 10.0 and 1.0 - 20.0 microg ml(-1) with detection limits of 0.6, 0.5 and 0.7 microg ml(-1) for thiamin, riboflavin and pyridoxal, respectively. The experimental calibration matrix was designed with 21 mixtures of these chemicals. The concentrations were varied between calibration graph concentrations of vitamins. The simultaneous determination of these vitamin mixtures by using spectrophotometric methods is a difficult problem, due to spectral interferences. The partial least squares (PLS) modeling and least-squares support vector machines were used for the multivariate calibration of the spectrophotometric data. An excellent model was built using LS-SVM, with low prediction errors and superior performance in relation to PLS. The root mean square errors of prediction (RMSEP) for thiamin, riboflavin and pyridoxal with PLS and LS-SVM were 0.6926, 0.3755, 0.4322 and 0.0421, 0.0318, 0.0457, respectively. The proposed method was satisfactorily applied to the rapid simultaneous determination of thiamin, riboflavin and pyridoxal in commercial pharmaceutical preparations and human plasma samples.

New Boron Analogues of Pyrophosphates and Deoxynucleoside Boranophosphates

PubMed Central

Vyakaranam, Kamesh; Rana, Geeta; Spielvogel, Bernard F.

2001-01-01

Tetraethyldicyanoborane pyrophosphate (2) and 3'-(diethylphosphite-cyanoborano)-5'-dimethoxytrityl.N4-benzoyl-deoxycytidine (3) have been synthesized in 70% and 76% yields, respectively. The compatibility of the substituted boranophosphates with common protecting groups is hereby demonstrated. Boron containing biologically active compounds, such as nucleosides and nucleotides 1-6 and amino acids 7-9 are important due to their potential therapeutic activity, research and diagnostic applications. Many boron containing compounds have shown promising activity as anticancer, 10. 11. 12 antiinflammatory,13 and antiosteoporotic 13agents. Oligonucleotdes in which a non-bridging oxygen atom is replaced by a borane(BH3) group are a very important class of modified nucleic acids. 1. 3. 14-16 The BH3 group is isoelectronic with oxygen in natural oligonucleotides and isoelectronic and isostructural with the oligonucleotide methyl phosphonates, which are nuclease resistant. On the other hand, the α-borano triphosphates are good substrates for DNA polymerases and incorporation of boranophosphates into DNA causes an increase in the resistance to exo- and endonucleases 2. 17a as compared to non-modified DNA. There are also notable applications of the α-borano triphosphates in PCR sequencing 17a and nucleic acid detection 17b. PMID:18475988

Increasing consumption of breakfast cereal improves thiamine status in overweight/obese women following a hypocaloric diet.

PubMed

Ortega, Rosa M; López-Sobaler, Ana M; Andrés, Pedro; Rodríguez-Rodríguez, Elena; Aparicio, Aránzazu; Bermejo, Laura M

2009-01-01

The aim of this study was to analyse the thiamine status in a group of young, overweight/obese women and to analyse the changes in this status produced by two weight-control programmes based on approximating the diet to the theoretical ideal, increasing the relative consumption of vegetables (V) or cereals (C) (especially breakfast cereals). The study subjects were 57 Spanish women with a body mass index (BMI) of 24-35 kg/m(2), all of whom were randomly assigned to one of two slightly hypocaloric diets. Dietetic, anthropometric and biochemical data were collected at the beginning of the study and at 2 and 6 weeks. C and V subjects showed a reduction in their energy intake, body weight and BMI, both at 2 and 6 weeks. Thiamine intake and blood thiamine levels only increased with diet C (both at 2 and 6 weeks). 21.8% cf the women, 21.8% had blood thiamine levels <150 nmol/L at the beginning of the study, but at 6 weeks of intervention only 3.7% of the women in diet C, as compared with 30.8% of the women in diet V, showed blood thiamine levels <150 nmol/L. Although both diet C and diet V induced weight loss and a reduction in BMI, diet C would appear to be more useful in the maintenance of an adequate thiamine status.

GC-MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows.

PubMed

Xue, Fuguang; Pan, Xiaohua; Jiang, Linshu; Guo, Yuming; Xiong, Benhai

2018-01-01

Thiamine is known to attenuate high-concentrate diet induced subacute ruminal acidosis (SARA) in dairy cows, however, the underlying mechanisms remain unclear. The major objective of this study was to investigate the metabolic mechanisms of thiamine supplementation on high-concentrate diet induced SARA. Six multiparous, rumen-fistulated Holstein cows were used in a replicated 3 × 3 Latin square design. The treatments included a control diet (CON; 20% starch, dry matter basis), a SARA-inducing diet (SAID; 33.2% starch, dry matter basis) and SARA-inducing diet supplemented with 180 mg of thiamine/kg of dry matter intake (SAID + T). On d21 of each period, ruminal fluid samples were collected at 3 h post feeding, and GC/MS was used to analyze rumen fluid samples. PCA and OPLS-DA analysis demonstrated that the ruminal metabolite profile were different in three treatments. Compared with CON treatment, SAID feeding significantly decreased rumen pH, acetate, succinic acid, increased propionate, pyruvate, lactate, glycine and biogenic amines including spermidine and putrescine. Thiamine supplementation significantly decreased rumen content of propionate, pyruvate, lactate, glycine and spermidine; increase rumen pH, acetate and some medium-chain fatty acids. The enrichment analysis of different metabolites indicated that thiamine supplementation mainly affected carbohydrates, amino acids, pyruvate and thiamine metabolism compared with SAID treatment. These findings revealed that thiamine supplementation could attenuate high-concentrate diet induced SARA by increasing pyruvate formate-lyase activity to promote pyruvate to generate acetyl-CoA and inhibit lactate generation. Besides, thiamine reduced biogenic amines to alleviate ruminal epithelial inflammatory response.

Electronic structure of lead pyrophosphate

NASA Astrophysics Data System (ADS)

Suewattana, Malliga; Singh, David

2007-03-01

Lead Pyrophosphate Pb2P2O7 is of interest for potential radiation detection applications and use in long term waste storage. It forms in triclinic P1 crystals and can also be grown as glasses. We performed electronic structure calculations using the crystal structure which determined by Mullica et. al (J. Solid State Chem (1986)) using x-ray diffraction and found large forces on atoms suggesting that the refined atomic positions were not fully correct. Here we report first principles structure relaxation and a revised crystal structure for this compound. We analyze the resulting structure using pair distribution functions and discuss the implications for the electronic properties. This work was supported by DOE NA22 and the Office of Naval Research.

Influence of diet of double-crested cormorants on thiamine, lead, and mineral contents of their eggs

USGS Publications Warehouse

Ketola, H. George; Johnson, James H.; Adams, C.M.; Farquhar, J.F.

2009-01-01

Throughout much of the Great Lakes basin, reproduction of several fish species is impaired by deficiency of thiamine in their eggs, an effect attributed to consumption of thiaminase-containing forage species, primarily alewife (Alosa pseudoharengus.) Because the double-crested cormorant (Phalacrocorax auritus) nesting on islands in Lake Ontario is known to consume considerable amounts of alewife, we examined cormorant food habits and measured thiamine content in eggs collected in 1999 from six separate nests of cormorants from colonies near Lake Ontario and contrasted them with food habits and eggs of cormorants from Oneida Lake where the alewife is rare. Thiamine concentrations in eggs varied between 4.31 and 11.24 nmoleslg with no significant (P>0.18) difference between mean concentrations for Lake Ontario and Oneida Lake (8.08 vs 8.36 nmoles/g) even though alewife comprised approximately 65 vs 0 % of their diets, respectively. Consumption of other thiaminase-containing species was minor in both lakes. Therefore, consumption of alewife and other thiaminase containing fishes by cormorants on Lake Ontario did not appear to significantly impair the levels of thiamine in their eggs. However, we found that the concentration of thiamine in eggs (T; nmoles/g) was inversely related (P<0.02) to lead (Pb) concentration (μg/g) according to the equation: T = −3.142 Pb + 16.25. This relationship may reflect the known ability of thiamine to chelate lead and increase its excretion.

Influence of diet of double-crested cormorants on thiamine, lead, and mineral contents of their eggs

USGS Publications Warehouse

Ketola, H.G.; Johnson, J. H.; Adams, C.M.; Farquhar, J.F.

2009-01-01

Throughout much of the Great Lakes basin, reproduction of several fish species is impaired by deficiency of thiamine in their eggs, an effect attributed to consumption of thiaminase-containing forage species, primarily alewife (Alosa pseudoharengus). Because the double-crested cormorant (Phalacrocorax auritus) nesting on islands in Lake Ontario is known to consume considerable amounts of alewife, we examined cormorant food habits and measured thiamine content in eggs collected in 1999 from six separate nests of cormorants from colonies near Lake Ontario and contrasted them with food habits and eggs of cormorants from Oneida Lake where the alewife is rare. Thiamine concentrations in eggs varied between 4.31 and 11.24 nmoles/g with no significant (P>0.18) difference between mean concentrations for Lake Ontario and Oneida Lake (8.08 vs 8.36 nmoles/g) even though alewife comprised approximately 65 vs 0 % of their diets, respectively. Consumption of other thiaminase-containing species was minor in both lakes. Therefore, consumption of alewife and other thiaminase containing fishes by cormorants on Lake Ontario did not appear to significantly impair the levels of thiamine in their eggs. However, we found that the concentration of thiamine in eggs (T; nmoles/g) was inversely related (P<0.02) to lead (Pb) concentration (µg/g) according to the equation: T = -3.142 Pb + 16.25. This relationship may reflect the known ability of thiamine to chelate lead and increase its excretion.

21 CFR 582.5306 - Ferric sodium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5306 - Ferric sodium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5306 - Ferric sodium pyrophosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5306 - Ferric sodium pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

PKR downregulation prevents neurodegeneration and β-amyloid production in a thiamine-deficient model.

PubMed

Mouton-Liger, F; Rebillat, A-S; Gourmaud, S; Paquet, C; Leguen, A; Dumurgier, J; Bernadelli, P; Taupin, V; Pradier, L; Rooney, T; Hugon, J

2015-01-15

Brain thiamine homeostasis has an important role in energy metabolism and displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD) induces regionally specific neuronal death in the animal and human brains associated with a mild chronic impairment of oxidative metabolism. These features make the TD model amenable to investigate the cellular mechanisms of neurodegeneration. Once activated by various cellular stresses, including oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the protein translation leading to an increase of BACE1 translation. In this study, we used a mouse TD model to assess the involvement of PKR in neuronal death and the molecular mechanisms of AD. Our results showed that the TD model activates the PKR-eIF2α pathway, increases the BACE1 expression levels of Aβ in specific thalamus nuclei and induces motor deficits and neurodegeneration. These effects are reversed by PKR downregulation (using a specific inhibitor or in PKR knockout mice).

PKR downregulation prevents neurodegeneration and β-amyloid production in a thiamine-deficient model

PubMed Central

Mouton-Liger, F; Rebillat, A-S; Gourmaud, S; Paquet, C; Leguen, A; Dumurgier, J; Bernadelli, P; Taupin, V; Pradier, L; Rooney, T; Hugon, J

2015-01-01

Brain thiamine homeostasis has an important role in energy metabolism and displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD) induces regionally specific neuronal death in the animal and human brains associated with a mild chronic impairment of oxidative metabolism. These features make the TD model amenable to investigate the cellular mechanisms of neurodegeneration. Once activated by various cellular stresses, including oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the protein translation leading to an increase of BACE1 translation. In this study, we used a mouse TD model to assess the involvement of PKR in neuronal death and the molecular mechanisms of AD. Our results showed that the TD model activates the PKR-eIF2α pathway, increases the BACE1 expression levels of Aβ in specific thalamus nuclei and induces motor deficits and neurodegeneration. These effects are reversed by PKR downregulation (using a specific inhibitor or in PKR knockout mice). PMID:25590804

Investigation of thiamine and PCB association with early life stage fry mortality in lake trout from northwestern Lake Michigan in 1996-1998

USGS Publications Warehouse

Honeyfield, Dale C.; Beltman, Dong; Holey, Mark; Edsall, Carol C.

2005-01-01

Lake trout (Salvelinus namaycush) eggs were collected from 72 females near Sturgeon Bay, WI in northwestern Lake Michigan from 1996, 1997, and 1998 to determine the relationships between egg thiamine and polychlorinated biphenyl (PCB) concentrations with egg fertilization and hatch, prevalence of abnormal fry, and fry mortality. Fry mortality consistent with early mortality syndrome (EMS) was observed in eggs from 33% of the females in 1996, 25% in 1997, and 28% in 1998. Among egg lots exhibiting EMS, fry mortality averaged 95% in 1996, 63% in 1997 and 77% in 1998 compared to 2% or less in lots that did not exhibit EMS. Expression of EMS was strongly correlated with egg thiamine concentrations; egg lots with less than approximately 1 nmol/g total thiamine consistently exhibited high rates of EMS, whereas egg batches with greater than 1.5 nmol/g showed little or no incidence of EMS among swim-up fry. Egg thiamine concentration was not related to fertilization rate, egg hatch, or the prevalence of abnormal fry. There was no relationship between egg concentrations of PCBs or tetrachlorinated dibenzo-p-dioxin (TCDD) equivalents (from PCBs, dioxins, and furans) and any of the egg or fry viability measurements, including EMS. We concluded that fry mortality observed in Lake Michigan lake trout in 1996-1998 was not caused by the toxicity of PCBs, dioxins, and furans, but is due to low egg thiamine concentrations.

Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?

PubMed Central

Harper, Clive G; Sheedy, Donna L; Lara, Ana I; Garrick, Therese M; Hilton, John M; Raisanen, Jack

2012-01-01

Objective To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Australia and compare this with previous studies. Design and setting Prospective autopsy study at the New South Wales Institute of Forensic Medicine, 1996-1997. Methods Brains of deceased people (aged over 15 years) derived from 2212 sequential autopsies performed between 1 January 1996 and 31 December 1997 were studied macroscopically and microscopically to identify cases of WKS. Main outcome measures Standard histological criteria for WKS and any available clinical data. Results Twenty-five cases of WKS were identified (prevalence, 1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of alcohol abuse. Only four cases (16%) had been diagnosed during life. Conclusions There has been a significant reduction in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour. While the prevalence is still higher than in most other Western countries, further research is needed before adding thiamine to alcoholic beverages can be recommended. PMID:9640303

Kinetic Fluorescence Experiment for the Determination of Thiamine.

ERIC Educational Resources Information Center

Bower, Nathan W.

1982-01-01

Background information, procedures, and typical results are provided for an experiment which integrates principles of fluorescent and kinetic analysis. In the procedure, mecuric chloride is used as a selective oxidizing agent for converting thiamine to thiochrome. The experiment can be completed in a two-hour laboratory period. (Author/JN)

Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

PubMed

Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

2018-02-02

Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate.

PubMed

Cercamondi, Colin I; Duchateau, Guus S M J E; Harika, Rajwinder K; van den Berg, Robin; Murray, Peter; Koppenol, Wieneke P; Zeder, Christophe; Zimmermann, Michael B; Moretti, Diego

2016-08-01

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Synthesis, characterization and properties of uridine 5'-( -D-apio-D-furanosyl pyrophosphate).

PubMed

Kindel, P K; Watson, R R

1973-06-01

1. A method was developed for synthesizing UDP-apiose [uridine 5'-(alpha-d-apio-d-furanosyl pyrophosphate)] from UDP-glucuronic acid [uridine 5'-(alpha-d-glucopyranosyluronic acid pyrophosphate)] in 62% yield with the enzyme UDP-glucuronic acid cyclase. 2. UDP-apiose had the same mobility as uridine 5'-(alpha-d-xylopyranosyl pyrophosphate) when chromatographed on paper and when subjected to paper electrophoresis at pH5.8. When [(3)H]UDP-[U-(14)C]glucuronic acid was used as the substrate for UDP-glucuronic acid cyclase, the (3)H/(14)C ratio in the reaction product was that expected if d-apiose remained attached to the uridine. In separate experiments doubly labelled reaction product was: (a) hydrolysed at pH2 and 100 degrees C for 15min; (b) degraded at pH8.0 and 100 degrees C for 3min; (c) used as a substrate in the enzymic synthesis of [(14)C]apiin. In each type of experiment the reaction products were isolated and identified and were found to be those expected if [(3)H]UDP-[U-(14)C]apiose was the starting compound. 3. Chemical characterization established that the product containing d-[U-(14)C]apiose and phosphate formed on alkaline degradation of UDP-[U-(14)C]apiose was alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate. 4. Chemical characterization also established that the product containing d-[U-(14)C]apiose and phosphate formed on acid hydrolysis of alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate was d-[U-(14)C]apiose 2-phosphate. 5. The half-life periods for the degradation of UDP-[U-(14)C]apiose to alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate and UMP at pH8.0 and 80 degrees C, at pH8.0 and 25 degrees C and at pH8.0 and 4 degrees C were 31.6s, 97.2min and 16.5h respectively. The half-life period for the hydrolysis of UDP-[U-(14)C]-apiose to d-[U-(14)C]apiose and UDP at pH3.0 and 40 degrees C was 4.67min. After 20 days at pH6.2-6.6 and 4 degrees C, 17% of the starting UDP-[U-(14)C]apiose was degraded to alpha-d-[U-(14)C

Thiamine content and thiaminase activity of ten freshwater stocks and one marine stock of alewives

USGS Publications Warehouse

Fitzsimons, J.D.; Williston, B.; Zajicek, J.L.; Tillitt, D.E.; Brown, S.B.; Brown, L.R.; Honeyfield, D.C.; Warner, D.M.; Rudstam, L. G.; Pearsall, W.

2005-01-01

Alewives Alosa pseudoharengus contain thiaminase activity that has been implicated in the development of a thiamine deficiency and associated effects in salmonines of the Great Lakes basin. Little is known about the factors that regulate thiaminase activity in alewives. We sampled alewives of uniform size (60-120 mm) during the summer of 1998 from the Gulf of St. Lawrence, seven of New York's Finger Lakes, one inland lake in Ontario, and two Great Lakes to assess possible relationships among thiamine, lipid content, fish abundance, lake morphometry, lake productivity, freshwater residency, and thiaminase activity. Thiaminase activity varied significantly among the 11 locations but was unrelated to thiamine concentration, which did not vary significantly. Alewife thiaminase activity in the Finger Lakes was negatively related to lipid content and positively related to measures of lake size (e.g., area, volume, and maximum depth). Activity in the one marine stock sampled in the Gulf of St. Lawrence was comparable to the highest values observed in the 10 freshwater stocks examined. Variation in alewife thiaminase activity has the potential to affect the extent of a thiamine deficiency associated with salmonines who feed on alewives as well as the viability of their offspring.

Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2

PubMed Central

Rao, Feng; Cha, Jiyoung; Xu, Jing; Xu, Risheng; Vandiver, M. Scott; Tyagi, Richa; Tokhunts, Robert; Koldobskiy, Michael A.; Fu, Chenglai; Barrow, Roxanne; Wu, Mingxuan; Fiedler, Dorothea; Barrow, James C.; Snyder, Solomon H.

2014-01-01

The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) co-chaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks) of which IP6K2 has been implicated in p53-associated cell death. In the present study we report a novel apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine-15 to activate the cell death program in human cancer cells and in murine B cells. PMID:24657168

Distinguishing erosive osteoarthritis and calcium pyrophosphate deposition disease.

PubMed

Rothschild, Bruce M

2013-04-18

Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis (non-erosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the "itis" suffix. The term "erosion" has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention.

Thiamin and riboflavin vitamers in human milk: effects of lipid-based nutrient supplementation and stage of lactation on vitamer secretion and contributions to total vitamin content

USDA-ARS?s Scientific Manuscript database

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main...

Apparent ruminal synthesis of B vitamins in lactating dairy cows fed diets with different forage-to-concentrate ratios.

PubMed

Seck, M; Linton, J A Voelker; Allen, M S; Castagnino, D S; Chouinard, P Y; Girard, C L

2017-03-01

Effects of the forage-to-concentrate ratio on apparent ruminal synthesis of thiamine, riboflavin, niacin, vitamin B 6 , folates, and vitamin B 12 were evaluated in an experiment using 14 ruminally and duodenally cannulated Holstein cows. The experiment was a crossover design with two 15-d treatment periods and a 14-d preliminary period in which cows were fed a diet intermediate in composition between the treatment diets. Treatments were diets containing low-forage (44.8% forage, 32.8% starch, 24.4% neutral detergent fiber) or high-forage (61.4% forage, 22.5% starch, 30.7% neutral detergent fiber) concentrations. Both diets were formulated with different proportions of the same ingredients. Concentrations of B vitamins were analyzed in feed and duodenal digesta. Apparent ruminal synthesis of each B vitamin was calculated as the duodenal flow minus the intake. The high-forage diet had the highest concentrations of riboflavin, niacin, vitamin B 6 , and folates, whereas the low-forage diet had the highest thiamine concentration. Vitamin B 12 in the diets was under the level of detection. Consequently, despite a reduction in dry matter intake when the cows were fed the high-forage diet, increasing dietary forage concentration increased or tended to increase intakes of riboflavin, niacin, and vitamin B 6 but reduced thiamine and folate intakes. Increasing dietary forage concentration reduced apparent ruminal degradation of thiamine and apparent ruminal synthesis of riboflavin, niacin, and folates and increased ruminal degradation of vitamin B 6 , but had no effect on ruminal synthesis of vitamin B 12 . As a consequence, increasing the forage-to-concentrate ratio had no effect on the amounts of thiamine, riboflavin, and vitamin B 12 reaching the small intestine but decreased the amounts of niacin, vitamin B 6 , and folates available for absorption. Apparent ruminal syntheses of riboflavin, niacin, folates, and vitamin B 12 were correlated positively with the amount of

Influence of naturally-occurring 5′-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: An X-ray crystallographic study

PubMed Central

Holloway, Daniel E; Chavali, Gayatri B; Leonidas, Demetres D; Baker, Matthew D; Acharya, K Ravi

2009-01-01

Ribonuclease A is the archetype of a functionally diverse superfamily of vertebrate-specific ribonucleases. Inhibitors of its action have potential use in the elucidation of the in vivo roles of these enzymes and in the treatment of pathologies associated therewith. Derivatives of adenosine 5′-pyrophosphate are the most potent nucleotide-based inhibitors known. Here, we use X-ray crystallography to visualize the binding of four naturally-occurring derivatives that contain 5′-pyrophosphate-linked extensions. 5′-ATP binds with the adenine occupying the B2 subsite in the manner of an RNA substrate but with the γ-phosphate at the P1 subsite. Diadenosine triphosphate (Ap3A) binds with the adenine in syn conformation, the β-phosphate as the principal P1 subsite ligand and without order beyond the γ-phosphate. NADPH and NADP+ bind with the adenine stacked against an alternative rotamer of His119, the 2′-phosphate at the P1 subsite, and without order beyond the 5′-α-phosphate. We also present the structure of the complex formed with pyrophosphate ion. The structural data enable existing kinetic data on the binding of these compounds to a variety of ribonucleases to be rationalized and suggest that as the complexity of the 5′-linked extension increases, the need to avoid unfavorable contacts places limitations on the number of possible binding modes. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 995–1008, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com PMID:19191310

Study of pyruvate decarboxylase and thiamine kinase from brewer's yeast by SERS

NASA Astrophysics Data System (ADS)

Maskevich, Sergei A.; Chernikevich, Ivan P.; Gachko, Gennedy A.; Kivach, Leonid N.; Strekal, Nataliya D.

1993-06-01

The Surface Enhanced Raman Scattering (SERS) spectra of holopyruvate decarboxylase (PDC) and thiamine kinase (ThK) adsorbed on silver electrode were obtained. In contrast to the Raman, the SERS spectrum of PDC contained no modes of tryptophan residues, it indicates a removal of this moiety from the surface. In the SERS spectrum of ThK the bands belonging to ligands bound to the protein were observed. A correlation between the SERS signal intensity and the enzymatic activity of the ThK separate fraction and found. The influence of amino acids on SERS spectra of thiamine (Th) was studied to determine the possible composition on microsurrounding of coenzyme.

Thiamine losses during storage of pasteurised and sterilized model systems of minced chicken meat with addition of fresh and oxidized fat, and antioxidants.

PubMed

Szymandera-Buszka, Krystyna; Hęś, Marzanna; Waszkowiak, Katarzyna; Jędrusek-Golińska, Anna

2014-01-01

The aim of the study was to determine the effect of pasteurisation and sterilization of model systems of minced chicken meat in the presence of low or high-oxidised pork lard, soy and sunflower oil, as well as casein hydrolysate and rosemary extract, on losses of thiamine in model systems. In the samples, the thiamine content was analysed periodically by thiochromium method, as well as rate of lipid oxidation based on measurement of peroxide value (PV) by iodometric method and p-anisidine value (AV) by spectrophotometric method. It was observed that the thiamine losses in model systems of minced chicken after pasteurisation (61-71%) were higher than after sterilization (57-67%). Introduction of high-oxidised fat increased the total thiamine losses both during thermal processing and storage of meat samples (to 23%). A strong relationship was established between thiamine losses and rate of fat oxidation. The lowest total thiamine losses were observed in the samples with low-oxidised pork lard. Antioxidant addition (rosemary extract or casein hydrolysate) into meat samples limited the thiamine losses. However, the effect depended on oxidation of fat that was mixed with meat. In the samples with low-oxidised fat, higher protective effect was found for rosemary extract (7-11%). In the samples with high-oxidised fat, casein hydrolysate was superior to rosemary extract (14%). In order to increase the stability of thiamine in pasteurized or sterilized meat products with fats, the influence of fat type and its oxidative stability should be taken under consideration. Moreover, the addition of rosemary extract or casein hydrolysate has impact on the thiamine losses since it slows down lipid oxidation to a significant extent.

Increase in lake trout reproduction in Lake Huron following the collapse of alewife: Relief from thiamine deficiency or larval predation?

USGS Publications Warehouse

Fitzsimons, J.D.; Brown, S.; Brown, L.; Honeyfield, D.; He, J.; Johnson, J.E.

2010-01-01

In the Great Lakes there is still uncertainty as to the population level effects of a thiamine deficiency on salmonines caused by high consumption of alewives Alosa pseudoharengus. A resurgence of lake trout Salvelinus namaycush reproduction in Lake Huron following the crash of alewife stocks between 2002 and 2004 provided an opportunity to evaluate the relative effects of this crash on reproduction through relief from either alewife mediated thiamine deficiency or alewife predation on larval lake trout relative to possible changes in the size of the lake trout spawning stock. Changes in mean lake trout egg thiamine concentration post crash at one spawning reef in Parry Sound, where mean thiamine concentration increased by almost two-fold, were consistent with diet switching from alewives to rainbow smelt Osmerus mordax, the next most abundant prey fish in Lake Huron. Although thiamine levels for lake trout collected at a second reef in Parry Sound did not change post-crash, levels both pre- and post-crash were consistent with a rainbow smelt diet. A reef specific fry emergence index was found to be positively related to reef specific egg thiamine concentration but negatively related to reef specific occurrence of EMS, a thiamine deficiency related mortality syndrome. We found little evidence for overlap between the timing of spring shoreward migration of alewives and lake trout emergence, suggesting that relief from alewife predation effects had relatively little effect on the observed increase in lake trout recruitment. Numbers of spawners in the north, north-central, and southern zones of the lake increased from 2000 onwards. Overall the abundance post-2003 was higher than from pre-2004, suggesting that spawner abundance may also have contributed to increased lake trout reproduction. However, predicted numbers of spawners and measured abundance of wild recruits in assessment gear were poorly correlated suggesting that the increase in reproduction was not totally

Distinguishing erosive osteoarthritis and calcium pyrophosphate deposition disease

PubMed Central

Rothschild, Bruce M

2013-01-01

Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis (non-erosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the “itis” suffix. The term “erosion” has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention. PMID:23610748

The selectivity of water-based pyrophosphate recognition is tuned by metal substitution in dimetallic receptors.

PubMed

Svane, Simon; Kjeldsen, Frank; McKee, Vickie; McKenzie, Christine J

2015-07-14

The three dimetallic compounds [Ga2(bpbp)(OH)2(H2O)2](ClO4)3, [In2(bpbp)(CH3CO2)2](ClO4)3 and [Zn2(bpbp)(HCO2)2](ClO4) (bpbp(-) = 2,6-bis((N,N'-bis(2-picolyl)amino)methyl)-4-tertbutylphenolate) were evaluated as stable solid state precursors for reactive solution state receptors to use for the recognition of the biologically important anion pyrophosphate in water at neutral pH. Indicator displacement assays using in situ generated complex-pyrocatechol violet adducts, {M2(bpbp)(HxPV)}(n+) M = Ga(3+), In(3+), Zn(2+), were tested for selectivity in their reactions with a series of common anions: pyrophosphate, phosphate, ATP, arsenate, nitrate, perchlorate, chloride, sulfate, formate, carbonate and acetate. The receptor employing Ga(3+) showed a slow but visually detectable response (blue to yellow) in the presence of one equivalent of pyrophosphate but no response to any other anion, even when they were present in much higher concentrations. The systems based on In(3+) or Zn(2+) show less selectivity in accord with visibly discernible responses to several of the anions. These results demonstrate a facile method for increasing anion selectivity without modification of an organic dinucleating ligand scaffold. The comfortable supramolecular recognition of pyrophosphate by the dimetallic complexes is demonstrated by the single crystal X-ray structure of [Ga2(bpbp)(HP2O7)](ClO4)2 in which the pyrophosphate is coordinated to the two gallium ions via four of its oxygen atoms.

Label-Free Pyrophosphate Recognition with Functionalized Asymmetric Nanopores.

PubMed

Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Niemeyer, Christof M; Mafe, Salvador; Ensinger, Wolfgang

2016-04-01

The label-free detection of pyrophosphate (PPi) anions with a nanofluidic sensing device based on asymmetric nanopores is demonstrated. The pore surface is functionalized with zinc complexes based on two di(2-picolyl)amine [bis(DPA)] moieties using carbodiimide coupling chemistry. The complexation of zinc (Zn(2+) ) ion is achieved by exposing the modified pore to a solution of zinc chloride to form bis(Zn(2+) -DPA) complexes. The chemical functionalization is demonstrated by recording the changes in the observed current-voltage (I-V) curves before and after pore modification. The bis(Zn(2+) -DPA) complexes on the pore walls serve as recognition sites for pyrophosphate anion. The experimental results show that the proposed nanofluidic sensor has the ability to sense picomolar concentrations of PPi anion in the surrounding environment. On the contrary, it does not respond to other phosphate anions, including monohydrogen phosphate, dihydrogen phosphate, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate. The experimental results are described theoretically by using a model based on the Poisson-Nernst-Planck equations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SEPARATION OF PLUTONIUM IONS FROM SOLUTION BY ADSORPTION ON ZIRCONIUM PYROPHOSPHATE

DOEpatents

Stoughton, R.W.

1961-01-31

A method is given for separating plutonium in its reduced, phosphate- insoluble state from other substances. It involves contacting a solution containing the plutonium with granular zirconium pyrophosphate.

Pathological and behavioral manifestations of the “Cayuga syndrome,” a thiamine deficiency in larval landlocked Atlantic salmon

USGS Publications Warehouse

Fisher, Jeffrey P.; Spitsbergen, Jan M.; Iamonte, Tina; Little, Edward E.; DeLonay, Aaron

1995-01-01

The “Cayuga syndrome” is a maternally transmitted, naturally occurring thiamine deficiency that causes 100% mortality of larval landlocked Atlantic salmon Salmo salar in several of New York's Finger Lakes, Results of multiyear studies to qualify and quantify the neurobehavioral and gross pathological signs of this condition are described, Affected sac fry became weak and ataxic and responded atypically to stimuli 1–2 weeks before death. Quantitative assays of stimulus-provoked swimming revealed a significant neuropathy whereby the sac fry exhibited abnormal thigmotactic and phototactic behaviors. Gross lesions observed in Cayuga sac fry included yolk-sac opacities, subcutaneous edema, vitelline hemorrhage or congestion, pericardial edema, retrobulbar edema, branchial congestion, foreshortened maxillae, hydrocephalus, and occasional caudal fin deformities, Lesion frequency in progeny differed significantly between dam source. Yolk conversion efficiency was decreased at least 1 week before death, suggesting that the bioenergetics of the fish was compromised and thereby supporting the thiamine residue and treatment data reported elsewhere, Comparisons with coagulated-yolk, blue-sac and swim-up syndromes are presented, The pathological signs of the Cayuga syndrome represent a unique departure from the lesions induced by toxicants or pathogens in other piscine models, and for the first time profile the profound effects of thiamine deficiency on cardiovascular and neurological systems of larval fish.

Particle length of silages affects apparent ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Kammes, K L; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2016-08-01

Effects of particle length of silages on apparent ruminal synthesis (ARS) and postruminal supply of B vitamins were evaluated in 2 feeding trials. Diets containing alfalfa (trial 1) or orchardgrass (trial 2) silages, chopped to either 19mm (long cut, LC) or 10mm (short cut, SC) theoretical particle length, as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. Forages chopped to a theoretical particle length of 19 and 10mm had mean particles sizes of 14.1 and 8.1mm, respectively, in trial 1, and 15.3 and 11.3mm, respectively, in trial 2. Trial 1 was conducted with 13 multiparous cows in two 19-d treatment periods; both diets contained approximately 20% forage neutral detergent fiber (NDF), 25% total NDF, and forage-to-concentrate ratios were approximately 47:53. Trial 2 was conducted with 15 cows in two 18-d treatment periods; both diets contained approximately 23% forage NDF, 28% total NDF, and had a forage-to-concentrate ratio of 50:50. Thiamine, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were measured in feed and duodenal content. Daily ARS was calculated as the duodenal flow minus the intake. In trial 1, daily intake of individual B vitamins was increased with the LC diet, but ARS of thiamine, riboflavin, vitamin B6, and folates was reduced. In trial 2, except for folates, intakes of the other B vitamins were decreased with the LC diets, whereas ARS of riboflavin, niacin, and vitamin B6 was increased. Daily ARS of thiamine, riboflavin, niacin, and vitamin B6 were correlated negatively with their intake, suggesting that ruminal bacteria reduced their synthesis when dietary supply increased. Microbial activity could have also reduced degradation of thiamine, riboflavin, and niacin, which is supported by (1) the negative correlation between ARS of these vitamins and ruminal pH or microbial N duodenal flow; and (2) the positive correlation between ARS and ruminal concentrations

Effect of flour extraction rate and baking on thiamine and riboflavin content and antioxidant capacity of traditional rye bread.

PubMed

Martinez-Villaluenga, C; Michalska, A; Frias, J; Piskula, M K; Vidal-Valverde, C; Zieliński, H

2009-01-01

The effect of rye flour extraction rates and baking on thiamine and riboflavin content, and antioxidant capacity of traditional rye bread were studied and compared with white wheat flour. The content of thiamine was higher (10.9%) in rye dough formulated with dark rye flour (F-100%; extraction rate of 100%) than in rye dough formulated with brown rye flour (F-92%; extraction rate of 92%) that was similar to dough made with wheat flour. The riboflavin content in rye dough made from flour F-100% was also higher (16%) than in dough formulated with flour F-92%, and both provided larger riboflavin content than wheat dough. Baking led to reductions in thiamine of 56% for wheat bread and of 20% for both rye breads; however, this process caused only a 10% decrease in riboflavin for wheat bread and a 30% decrease for rye breads. Trolox equivalent antioxidant capacity, peroxyl radical scavenging capacity, DPPH radical scavenging activity, and Folin-Ciocalteu reducing capacity were higher in rye than in wheat dough and bread. Baking process produced slight changes in antioxidant activity, except for Superoxide Dismutase-like activity where a sharp decrease was observed. Our findings showed that rye breads are an important source of B vitamins and rye breads formulated with dark and brown flours showed better antioxidant properties than wheat bread. Therefore, rye breads should be more widely recommended in human nutrition.

Effect of thiamine concentration on animal health, feedlot performance, carcass characteristics, and ruminal hydrogen sulfide concentrations in lambs fed diets based on 60% distillers dried grains plus solubles.

PubMed

Neville, B W; Schauer, C S; Karges, K; Gibson, M L; Thompson, M M; Kirschten, L A; Dyer, N W; Berg, P T; Lardy, G P

2010-07-01

Limited data are available regarding the influence of thiamine supplementation on the incidence of polioencephalomalacia (PEM) in lambs fed diets containing increased concentrations of S in the diet (>0.7%). Therefore, our objective was to evaluate the influence of thiamine supplementation on feedlot performance, carcass quality, ruminal hydrogen sulfide gas concentrations, and incidence of PEM in lambs fed a finishing diet containing 60% distillers dried grains with solubles (DDGS; DM basis). Two studies were conducted using completely randomized designs to evaluate the influence of concentration of thiamine supplementation. Study 1 used 240 lambs fed in 16 pens, whereas study 2 used 55 individually fed lambs. Lamb finishing diets contained 60% DDGS, which resulted in a dietary S concentration of 0.73% (DM basis). Treatments diets were based on the amount of supplemental thiamine provided: 1) no supplemental thiamine (CON), 2) 50 mg/animal per day (LO), 3) 100 mg/animal per day (MED), or 4) 150 mg/animal per day (HI). Additionally, in study 2, a fifth treatment was included, which contained 0.87% S (DM basis; increased S provided by addition of dilute sulfuric acid) and provided 150 mg of thiamine/animal per day (HI+S). In study 1, ADG decreased quadratically (P = 0.04), with lambs fed the CON, LO, and MED diets gaining BW at a greater rate than lambs fed the HI diet. In study 1, DMI responded quadratically (P < 0.01), whereas G:F tended to differ linearly (P = 0.08) to concentration of thiamine supplementation, with MED lambs having greater DMI and decreased G:F. No differences (P > or = 0.17) in lamb performance were observed in study 2. In both studies, most carcass characteristics were unaffected, with the exception of a tendency for decreased carcass conformation (study 1; P = 0.09) and greater flank streaking (study 2; P = 0.03). No differences in ruminal hydrogen sulfide concentration (P > 0.05) among treatments were apparent until d 10, at which point

Effect of thiamine hydrochloride on the redox reactions of iron at pyrite surface

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

Pesic, B.; Oliver, D.J.

1990-01-01

The present investigation is a part of our studies on the electro chemical aspects of pyrite bioleaching involving Thiobacillus ferrooxidans. Previously (1,2) we have examined the effect of T. ferrooxidans and their metabolic products on the redox reactions of Fe[sup 2+]/Fe[sup 3+] couple at the pyrite surface. Results obtained suggest that beyond 1. 5 days during their growth in a batch fermenter, the bacteria and their metabolic products completely cover the pyrite surface and shut down all electron transfer across the electrode-solution interface. In addition, it has been observed that the bacteria serve as the nucleation site for jarosite formation,more » which is found detrimental to bioleaching. In the present work we have focussed on the effect of the presence of vitamins on the redox chemistry of iron. Our examination of the effect of the presence of thiamine hydrochloride in the redox behavior of Fe[sup 2+]/Fe[sup 3+] at the pyrite surface has revealed that thiamine hydrochloride does not undergo chemical interaction with ferrous or ferric iron. However, it may adsorb onto the pyrite surface causing polarization of the pyrite electrode.« less

Consideration of alternative causes of lactic acidosis: Thiamine deficiency in malignancy.

PubMed

Dean, Ryan K; Subedi, Rogin; Gill, Dalvir; Nat, Amitpal

2017-08-01

Lactic acidosis is a common metabolic acidosis characterized by increased serum lactate and is usually associated with a decreased blood pH. Lactic acidosis has many different causes but has been differentiated into type A, hypoxic causes, and type B, non-hypoxic causes. Tissue hypoxia, type A, is the most common cause, usually secondary to processes such as sepsis and multi-organ failure. Type A must be differentiated from type B in the correct clinical setting as treatments are vastly different. Type B causes may include drug side-effects, toxins, enzymatic defects, inherited or acquired, any of which may lead to overproduction or underutilization of lactate. However, as most clinicians are more familiar, and likely more initially concerned with hypoxic etiologies, evaluation is directed toward finding the source of hypoperfusion or hypoxia, and thus generally leading to a delay in discovering a type B cause (or mixed type A and type B). Here we describe a case of lactic acidosis in the setting of thiamine deficiency thought to be secondary to advanced lung cancer. The purpose of this paper is to bring awareness to the clinician to consider other causes of lactic acidosis when evaluating a patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Thiamin is decomposed due to Anaphe spp. entomophagy in seasonal ataxia patients in Nigeria.

PubMed

Nishimune, T; Watanabe, Y; Okazaki, H; Akai, H

2000-06-01

A fairly high activity of a relatively heat-resistant thiaminase was detected and characterized from the pupae of an African silkworm Anaphe spp. which had been the putative cause of a seasonal ataxia and impaired consciousness in Nigerians. The thiaminase in the buffer extract of Anaphe pupae was type I (thiamin: base 2-methyl-4-aminopyrimidine methyl transferase EC 2.5.1.2), and the optimal temperature and pH were 70 degrees C and 8.0-8.5, respectively. Based on gel filtration chromatography, the molecules were estimated to be 200 kDa. Second substrates which could be utilized by the thiaminase were pyridoxine, amino acids, glutathione, taurine and 4-aminopyridine. Thiamin phosphate esters were inactive as substrates. This is the first report describing an insect thiaminase. Our results indicate the necessity of thorough heat treatment for the detoxification of the African silkworm, making the worm a safe source of high-quality protein.

From crystalline to amorphous calcium pyrophosphates: A solid state Nuclear Magnetic Resonance perspective.

PubMed

Gras, Pierre; Baker, Annabelle; Combes, Christèle; Rey, Christian; Sarda, Stéphanie; Wright, Adrian J; Smith, Mark E; Hanna, John V; Gervais, Christel; Laurencin, Danielle; Bonhomme, Christian

2016-02-01

Hydrated calcium pyrophosphates (CPP, Ca2P2O7·nH2O) are a fundamental family of materials among osteoarticular pathologic calcifications. In this contribution, a comprehensive multinuclear NMR (Nuclear Magnetic Resonance) study of four crystalline and two amorphous phases of this family is presented. (1)H, (31)P and (43)Ca MAS (Magic Angle Spinning) NMR spectra were recorded, leading to informative fingerprints characterizing each compound. In particular, different (1)H and (43)Ca solid state NMR signatures were observed for the amorphous phases, depending on the synthetic procedure used. The NMR parameters of the crystalline phases were determined using the GIPAW (Gauge Including Projected Augmented Wave) DFT approach, based on first-principles calculations. In some cases, relaxed structures were found to improve the agreement between experimental and calculated values, demonstrating the importance of proton positions and pyrophosphate local geometry in this particular NMR crystallography approach. Such calculations serve as a basis for the future ab initio modeling of the amorphous CPP phases. The general concept of NMR crystallography is applied to the detailed study of calcium pyrophosphates (CPP), whether hydrated or not, and whether crystalline or amorphous. CPP are a fundamental family of materials among osteoarticular pathologic calcifications. Their prevalence increases with age, impacting on 17.5% of the population after the age of 80. They are frequently involved or associated with acute articular arthritis such as pseudogout. Current treatments are mainly directed at relieving the symptoms of joint inflammation but not at inhibiting CPP formation nor at dissolving these crystals. The combination of advanced NMR techniques, modeling and DFT based calculation of NMR parameters allows new original insights in the detailed structural description of this important class of biomaterials. Copyright © 2016. Published by Elsevier Ltd.

Ultra-performance liquid chromatography tandem mass-spectrometry (uplc-ms/ms) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk

USDA-ARS?s Scientific Manuscript database

A novel, rapid and sensitive Ultra Performance Liquid-Chromatography tandem Mass-Spectrometry (UPLC-MS/MS) method for the simultaneous determination of several B-vitamins in human milk was developed. Resolution by retention time or multiple reaction monitoring (MRM) for thiamin, riboflavin, flavin a...

Synthesis, characterization and properties of uridine 5′-(α-d-apio-d-furanosyl pyrophosphate)

PubMed Central

Kindel, Paul K.; Watson, Ronald R.

1973-01-01

1. A method was developed for synthesizing UDP-apiose [uridine 5′-(α-d-apio-d-furanosyl pyrophosphate)] from UDP-glucuronic acid [uridine 5′-(α-d-glucopyranosyluronic acid pyrophosphate)] in 62% yield with the enzyme UDP-glucuronic acid cyclase. 2. UDP-apiose had the same mobility as uridine 5′-(α-d-xylopyranosyl pyrophosphate) when chromatographed on paper and when subjected to paper electrophoresis at pH5.8. When [3H]UDP-[U-14C]glucuronic acid was used as the substrate for UDP-glucuronic acid cyclase, the 3H/14C ratio in the reaction product was that expected if d-apiose remained attached to the uridine. In separate experiments doubly labelled reaction product was: (a) hydrolysed at pH2 and 100°C for 15min; (b) degraded at pH8.0 and 100°C for 3min; (c) used as a substrate in the enzymic synthesis of [14C]apiin. In each type of experiment the reaction products were isolated and identified and were found to be those expected if [3H]UDP-[U-14C]apiose was the starting compound. 3. Chemical characterization established that the product containing d-[U-14C]apiose and phosphate formed on alkaline degradation of UDP-[U-14C]apiose was α-d-[U-14C]apio-d-furanosyl 1:2-cyclic phosphate. 4. Chemical characterization also established that the product containing d-[U-14C]apiose and phosphate formed on acid hydrolysis of α-d-[U-14C]apio-d-furanosyl 1:2-cyclic phosphate was d-[U-14C]apiose 2-phosphate. 5. The half-life periods for the degradation of UDP-[U-14C]apiose to α-d-[U-14C]apio-d-furanosyl 1:2-cyclic phosphate and UMP at pH8.0 and 80°C, at pH8.0 and 25°C and at pH8.0 and 4°C were 31.6s, 97.2min and 16.5h respectively. The half-life period for the hydrolysis of UDP-[U-14C]-apiose to d-[U-14C]apiose and UDP at pH3.0 and 40°C was 4.67min. After 20 days at pH6.2–6.6 and 4°C, 17% of the starting UDP-[U-14C]apiose was degraded to α-d-[U-14C]apio-d-furanosyl 1:2-cyclic phosphate and UMP and 23% was hydrolysed to d-[U-14C]apiose and UDP. After 120 days at p

Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

PubMed Central

Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

2013-01-01

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID:24235882

Titanium Pyrophosphate for Removal of Trivalent Heavy Metals and Actinides Simulated by Retention of Europium

PubMed Central

Flores-Espinosa, Rosa María; Ordoñez-Regil, Eduardo; Fernández-Valverde, Suilma Marisela

2017-01-01

This work addresses the synthesis of titanium pyrophosphate, as well as the characterization and evaluation of the sorption process of europium, for removal of trivalent heavy metals and actinides simulate. The evaluation of the surface properties of titanium pyrophosphate was carried out determining the surface roughness and surface acidity constants. The values obtained from the determination of the surface roughness of the synthesized solid indicate that the surface of the material presents itself as slightly smooth. The FITEQL program was used to fit the experimental titration curves to obtain the surface acidity constants: log⁡K+ = 3.59 ± 0.06 and log⁡K− = −3.90 ± 0.05. The results of sorption kinetics evidenced that the pseudo-order model explains the retention process of europium, in which the initial sorption velocity was 8.3 × 10−4 mg g−1 min−1 and kinetic constant was 1.8 × 10−3 g mg min−1. The maximum sorption capacity was 0.6 mg g−1. The results obtained from sorption edge showed the existence of two bidentate complexes on the surface. PMID:28785720

Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

PubMed

Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

2011-06-01

Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Identification of the thiamin pyrophosphokinase gene in rainbow trout: Characteristic structure and expression of seven splice variants in tissues and cell lines and during embryo development

USGS Publications Warehouse

Yuge, Shinya; Richter, Catherine A.; Wright-Osment, Maureen K.; Nicks, Diane; Saloka, Stephanie K.; Tillitt, Donald E.; Li, Weiming

2012-01-01

Thiamin pyrophosphokinase (TPK) converts thiamin to its active form, thiamin diphosphate. In humans, TPK expression is down-regulated in some thiamin deficiency related syndrome, and enhanced during pregnancy. Rainbow trout are also vulnerable to thiamin deficiency in wild life and are useful models for thiamin metabolism research. We identified the tpk gene transcript including seven splice variants in the rainbow trout. Almost all cell lines and tissues examined showed co-expression of several tpk splice variants including a potentially major one at both mRNA and protein levels. However, relative to other tissues, the longest variant mRNA expression was predominant in the ovary and abundant in embryos. During embryogenesis, total tpk transcripts increased abruptly in early development, and decreased to about half of the peak shortly after hatching. In rainbow trout, the tpk transcript complex is ubiquitously expressed for all tissues and cells examined, and its increase in expression could be important in the early-middle embryonic stages. Moreover, decimated tpk expression in a hepatoma cell line relative to hepatic and gonadal cell lines appears to be consistent with previously reported down-regulation of thiamin metabolism in cancer.

Redox Additive-Improved Electrochemically and Structurally Robust Binder-Free Nickel Pyrophosphate Nanorods as Superior Cathode for Hybrid Supercapacitors.

PubMed

Sankar, Kalimuthu Vijaya; Seo, Youngho; Lee, Su Chan; Chan Jun, Seong

2018-03-07

For several decades, one of the great challenges for constructing a high-energy supercapacitor has been designing electrode materials with high performance. Herein, we report for the first time to our knowledge a novel hybrid supercapacitor composed of battery-type nickel pyrophosphate one-dimensional (1D) nanorods and capacitive-type N-doped reduced graphene oxide as the cathode and anode, respectively, in an aqueous redox-added electrolyte. More importantly, ex situ microscopic images of the nickel pyrophosphate 1D nanorods revealed that the presence of the battery-type redox additive enhanced the charge storage capacity and cycling life as a result of the microstructure stability. The nickel pyrophosphate 1D nanorods exhibited their maximum specific capacitance (8120 mF cm -2 at 5 mV s -1 ) and energy density (0.22 mWh cm -2 at a power density of 1.375 mW cm -2 ) in 1 M KOH + 75 mg K 3 [Fe(CN) 6 ] electrolyte. On the other side, the N-doped reduced graphene oxide delivered an excellent electrochemical performance, demonstrating that it was an appropriate anode. A hybrid supercapacitor showed a high specific capacitance (224 F g -1 at a current density of 1 A g -1 ) and high energy density (70 Wh kg -1 at a power density of 750 W kg -1 ), as well as a long cycle life (a Coulombic efficiency of 96% over 5000 cycles), which was a higher performance than most of those in recent reports. Our results suggested that the materials and redox additive in this novel design hold great promise for potential applications in a next-generation hybrid supercapacitor.

Vitamin B1 and B6 method harmonization: comparison of performance between laboratories enrolled in the RCPA Quality Assurance Program.

PubMed

Hoad, Kirsten E; Johnson, Lambro A; Woollard, Gerald A; Walmsley, Trevor A; Briscoe, Scott; Jolly, Lisa M; Gill, Janice P; Greaves, Ronda F

2013-06-01

The RCPA Quality Assurance Program (RCPA QAP) offers monthly proficiency testing for vitamins A, B1, B6, β-carotene, C and E to laboratories worldwide. A review of the results submitted for the whole blood vitamin B1/B6 sub-program revealed a wide dispersion. Here we describe the results of a methodology survey for vitamins B1 and B6. A questionnaire was sent to thirteen laboratories. Eleven laboratories were returning QAP results for vitamin B1 (thiamine diphosphate) and five were returning results for vitamin B6 (pyridoxal-5-phosphate). All nine respondents provided a clinical service for vitamins B1 and B6. HPLC with fluorescence detection was the most common method principle. For vitamin B1, six respondents used a commercial assay whilst three used in-house methods; whole blood was the matrix for all. For vitamin B6, five respondents used commercial assays and four used in-house assays. The choice of matrix for vitamin B6 varied with three respondents using whole blood and five using plasma for analysis. Sample preparation incorporated protein precipitation and derivatization steps. An internal standard was employed in sample preparation by only one survey respondent. The immediate result of this survey was the incorporation of plasma vitamin B6 into the RCPA QAP vitamin program. The absence of an internal standard in current vitamin B1 and B6 assays is a likely contributor to the wide dispersion of results seen in this program. We recommend kit manufacturers and laboratories investigate the inclusion of internal standards to correct the variability that may occur during processing. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Simple tools for assembling and searching high-density picolitre pyrophosphate sequence data.

PubMed

Parker, Nicolas J; Parker, Andrew G

2008-04-18

The advent of pyrophosphate sequencing makes large volumes of sequencing data available at a lower cost than previously possible. However, the short read lengths are difficult to assemble and the large dataset is difficult to handle. During the sequencing of a virus from the tsetse fly, Glossina pallidipes, we found the need for tools to search quickly a set of reads for near exact text matches. A set of tools is provided to search a large data set of pyrophosphate sequence reads under a "live" CD version of Linux on a standard PC that can be used by anyone without prior knowledge of Linux and without having to install a Linux setup on the computer. The tools permit short lengths of de novo assembly, checking of existing assembled sequences, selection and display of reads from the data set and gathering counts of sequences in the reads. Demonstrations are given of the use of the tools to help with checking an assembly against the fragment data set; investigating homopolymer lengths, repeat regions and polymorphisms; and resolving inserted bases caused by incomplete chain extension. The additional information contained in a pyrophosphate sequencing data set beyond a basic assembly is difficult to access due to a lack of tools. The set of simple tools presented here would allow anyone with basic computer skills and a standard PC to access this information.

Intensification of ion exchange desorption of thiamine diphosphate by low-powered ultrasound.

PubMed

Pinchukova, Natalia A; Voloshko, Alexander Y; Merko, Maria A; Bondarenko, Yana A; Chebanov, Valentin A

2018-03-01

The process of ultrasound-assisted ion-exchange desorption of cocarboxylase (thiamine diphosphate (TDP)) from a strong acidic cation resin was studied. Kinetics studies revealed that ultrasound accelerates TDP desorption by 3 times. The optimal desorption parameters, viz. US power input, sonication time, eluent/resin ratio and the eluent (ammonium acetate buffer) concentration were established which were 15mW/cm 3 , 20min, 1:1 and 1M, respectively. The resin stability studies showed that the optimal ultrasonic power was less by the order than the resin degradation threshold which ensures durable and efficient resin exploitation during production. The resin sorption capacity remained unchanged even after 20 cycles of TDP sorption, ultrasonic desorption and resin regeneration. The recovery ratio of TDP was shown to increase non-linearly with decreasing the resin saturation factor, which can be attributed to diffusion limitations occurring during desorption. The optimal resin loading corresponding to more than 90 per cent of TDP recovery was found to be at the level of 10 per cent of the maximal sorption capacity. The study revealed 4-5-fold increase in concentrations of the recovered solutions, which together with process times shortening should result in considerable energy saving in downstream operations on production scale. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure analysis of geranyl pyrophosphate methyltransferase and the proposed reaction mechanism of SAM-dependent C-methylation.

PubMed

Ariyawutthiphan, Orapin; Ose, Toyoyuki; Minami, Atsushi; Shinde, Sandip; Sinde, Sandip; Tsuda, Muneya; Gao, Yong-Gui; Yao, Min; Oikawa, Hideaki; Tanaka, Isao

2012-11-01

In the typical isoprenoid-biosynthesis pathway, condensation of the universal C(5)-unit precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) occurs via the common intermediates prenyl pyrophosphates (C(10)-C(20)). The diversity of isoprenoids reflects differences in chain length, cyclization and further additional modification after cyclization. In contrast, the biosynthesis of 2-methylisonorneol (2-MIB), which is responsible for taste and odour problems in drinking water, is unique in that it primes the enzymatic methylation of geranyl pyrophosphate (GPP) before cyclization, which is catalyzed by an S-adenosyl-L-methionine-dependent methyltransferase (GPPMT). The substrate of GPPMT contains a nonconjugated olefin and the reaction mechanism is expected to be similar to that of the steroid methyltransferase (SMT) family. Here, structural analysis of GPPMT in complex with its cofactor and substrate revealed the mechanisms of substrate recognition and possible enzymatic reaction. Using the structures of these complexes, methyl-group transfer and the subsequent proton-abstraction mechanism are discussed. GPPMT and SMTs contain a conserved glutamate residue that is likely to play a role as a general base. Comparison with the reaction mechanism of the mycolic acid cyclopropane synthase (MACS) family also supports this result. This enzyme represented here is the first model of the enzymatic C-methylation of a nonconjugated olefin in the isoprenoid-biosynthesis pathway. In addition, an elaborate system to avoid methylation of incorrect substrates is proposed.

Natural Versus Synthetic Vitamin B Complexes in Human

ClinicalTrials.gov

2018-04-12

Healthy; Thiamine and Niacin Deficiency States; Pyridoxine Deficiency; Folic Acid Deficiency Anemia, Dietary; Vitamin B 12 Deficiency; Peroxidase; Defect; Polyphenols; Oxidative Stress; Homocystine; Metabolic Disorder

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

PubMed Central

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-01-01

Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

PubMed

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-12-01

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

[Neurotropic effect of B vitamins in the complex treatment of pain syndrome].

PubMed

Shavlovskaya, O A

Combined vitamin preparations in therapeutic doses are used, along with simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle and epidural blockade, for the relief of acute pain. It is recommended to use the B vitamin preparation neuromultivit. The tablet form of this preparation contains vitamin thiamine hydrochloride (100 mg), pyridoxine hydrochloride (200 mg), cyanocobalamin (0.2 mg), and injectable form includes thiamine hydrochloride (100mg), pyridoxine hydrochloride (100 mg), cyanocobalamin (1 mg). The efficacy of neuromultivit in a two stage scheme (intramuscular injections of 2 ml daily for 5-10 days with further injections 2-3 times a week for 2-3 weeks at the initial stage and 1 tablet 3 times a day for 4 weeks at the second stage) was shown.

Insight into the ionotropic gelation of chitosan using tripolyphosphate and pyrophosphate as cross-linkers.

PubMed

Sacco, Pasquale; Paoletti, Sergio; Cok, Michela; Asaro, Fioretta; Abrami, Michela; Grassi, Mario; Donati, Ivan

2016-11-01

Ionotropic gelation of chitosan by means of opposite charged ions represents an efficient alternative to covalent reticulation because of milder condition of use and, in general, higher biocompatibility of the resulting systems. In this work 90° light scattering (turbidimetry), circular dichroism (CD) and 1 H NMR measurements have been performed to study the interactions between the biopolymer and ionic cross-linkers tripolyphosphate (TPP) and pyrophosphate (PPi) in dilute solutions. Thereafter, a dialysis-based technique was exploited to fabricate tridimensional chitosan hydrogels based on both polyanions. Resulting matrices showed a different mechanical behavior because of their peculiar mesh-texture at micro/nano-scale: in the present contribution we demonstrate that TPP and PPi favor the formation of homogeneous and inhomogeneous systems, respectively. The different texture of networks could be exploited in future for the preparation of systems for the controlled release of molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluorenone based fluorescent probe for selective "turn-on" detection of pyrophosphate and alanine

NASA Astrophysics Data System (ADS)

Daniel Thangadurai, T.; Nithya, I.; Manjubaashini, N.; Bhuvanesh, N.; Bharathi, G.; Nandhakumar, R.; Nataraj, D.

2018-06-01

To sense biologically important entities with different size and dimensions, a fluorenone based fluorescent receptor was designed and synthesized. Probe 1 displayed a distinct fluorescence enhancement emission at 565 nm for pyrophosphate and 530 nm for alanine in polar solvent. The fluorescence titration experiments confirm 1:1 stoichiometric ratio with high-binding constant and very low limit of detection (LoD) values. Receptor 1 showed a highly selective and sensitive recognition to HP2O73 - and to alanine over other competitive anions and amino acids. In addition, the fluorescence lifetime measurement and reversible binding study results support the practical importance of 1.

Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study.

PubMed

Filippucci, E; Riveros, M Gutierrez; Georgescu, D; Salaffi, F; Grassi, W

2009-02-01

The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.

Biosynthesis of o-succinylbenzoic acid in Bacillus subtilis: identification of menD mutants and evidence against the involvement of the alpha-ketoglutarate dehydrogenase complex.

PubMed Central

Palaniappan, C; Taber, H; Meganathan, R

1994-01-01

The biosynthesis of o-succinylbenzoic acid (OSB), the first aromatic intermediate involved in the biosynthesis of menaquinone (vitamin K2) is demonstrated for the first time in the gram-positive bacterium Bacillus subtilis. Cell extracts were found to contain isochorismate synthase, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (SHCHC) synthase-alpha-ketoglutarate decarboxylase and o-succinylbenzoic acid synthase activities. An odhA mutant which lacks the decarboxylase component (usually termed E1, EC 1.2.4.2, oxoglutarate dehydrogenase [lipoamide]) of the alpha-ketoglutarate dehydrogenase complex was found to synthesize SHCHC and form succinic semialdehyde-thiamine pyrophosphate. Thus, the presence of an alternate alpha-ketoglutarate decarboxylase activity specifically involved in menaquinone biosynthesis is established for B. subtilis. A number of OSB-requiring mutants were also assayed for the presence of the various enzymes involved in the biosynthesis of OSB. All mutants were found to lack only the SHCHC synthase activity. PMID:8169214

Giant geode (subchondrial cyst) in calcium pyrophosphate deposition disease on the curist.

PubMed

Weinberg, S; Scott, R A

1981-09-01

It is important to be aware of the radiographic features of pyrophosphate arthropathy with or without associated chondrocalcinosis. Accordingly, when appropriate structural joint changes are present an extraordinarily large subchondral cyst should not prompt a misdiagnosis of cystic tumor.

STUDIES ON CHEMICAL PROTECTION AGAINST X-RAY INJURIES. I. EFFECT OF VIT. B$sub 1$ AND THIAMINE PROPYL DISULPHIDE (ALINAMIN)

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

Hashimoto, T.

F/sub 1/ (ddms x C/sub 57/Bl/6) mice were given x irradiation of 800 r (LD/sub 100/) and 680 r (LD/sub 50/) and the protective effect of vit. B/sub 1/ and alinamin on the irradiation injuries was observed in mice on a vit. B /sub 1/ -deficent diet and in those receiving a temporary overdosage of alinanmin. Mice of the /sub 1/ strain had the advantages of hereditary homogeneity, prolificity, small dispersion. good growth,and low mortality under various external stresses. A difference in x-ray sensitivity between the two sexes was noted. Mice of the same age must be used for themore » experiment. Their x-ray sensitiviaty was increased by vit. B/sub 1/ deficiency; this increase was even more marked when a vit. B/ sub 1/-deficient diet was fed after the irradiation. The protective effect of vit. B/sub/1 depended on the method of administration. In mice given a 2 mg of vit. B/sub 1/ after irradiation, the survival rate was l00%. The effectiveness seemed to be due to the supplementation of vit. B/sub 1/ destruction. co- carboxylase function, and the supplying of an SH radical in the oxidationreduction system, which is produced by intrahepatic activation of the S an vit. B/sub 1/. X-ray sensitivity was increased in mice receiving a transitory overdose of alinamin. It may be that transformed alinamin increased the indirect action of x-rays. as an oxidizing agent. (Abstr. Japan Med, 1; No. l2. l96l)« less

Site-specific transition metal occupation in multicomponent pyrophosphate for improved electrochemical and thermal properties in lithium battery cathodes: a combined experimental and theoretical study.

PubMed

Shakoor, Rana A; Kim, Heejin; Cho, Woosuk; Lim, Soo Yeon; Song, Hannah; Lee, Jung Woo; Kang, Jeung Ku; Kim, Yong-Tae; Jung, Yousung; Choi, Jang Wook

2012-07-18

As an attempt to develop lithium ion batteries with excellent performance, which is desirable for a variety of applications including mobile electronics, electrical vehicles, and utility grids, the battery community has continuously pursued cathode materials that function at higher potentials with efficient kinetics for lithium insertion and extraction. By employing both experimental and theoretical tools, herein we report multicomponent pyrophosphate (Li(2)MP(2)O(7), M = Fe(1/3)Mn(1/3)Co(1/3)) cathode materials with novel and advantageous properties as compared to the single-component analogues and other multicomponent polyanions. Li(2)Fe(1/3)Mn(1/3)Co(1/3)P(2)O(7) is formed on the basis of a solid solution among the three individual transition-metal-based pyrophosphates. The unique crystal structure of pyrophosphate and the first principles calculations show that different transition metals have a tendency to preferentially occupy either octahedral or pyramidal sites, and this site-specific transition metal occupation leads to significant improvements in various battery properties: a single-phase mode for Li insertion/extraction, improved cell potentials for Fe(2+)/Fe(3+) (raised by 0.18 eV) and Co(2+)/Co(3+) (lowered by 0.26 eV), and increased activity for Mn(2+)/Mn(3+) with significantly reduced overpotential. We reveal that the favorable energy of transition metal mixing and the sequential redox reaction for each TM element with a sufficient redox gap is the underlying physical reason for the preferential single-phase mode of Li intercalation/deintercalation reaction in pyrophosphate, a general concept that can be applied to other multicomponent systems. Furthermore, an extremely small volume change of ~0.7% between the fully charged and discharged states and the significantly enhanced thermal stability are observed for the present material, the effects unseen in previous multicomponent battery materials.

Soft-tissue sarcoma: imaged with technetium-99m pyrophosphate

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

Blatt, C.J.; Hayt, D.B.; Desai, M.

1977-11-01

A liposarcoma showed intense concentration of technetium-99m pyrophosphate. An angiogram demonstrated a highly vascular lesion, and it is suggested that blood flow played a major role in allowing the tumor to be demonstrated on scintiphotography. There was some histologic evidence of calcification which probably also contributed to bone-tracer disposition. Quantitative analysis of the specimen demonstrated that this calcification was located primarily in the areas of hemorrhage and necrosis.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Tryptophan, thiamine and indole-3-acetic acid exchange between Chlorella sorokiniana and the plant growth-promoting bacterium Azospirillum brasilense.

PubMed

Palacios, Oskar A; Gomez-Anduro, Gracia; Bashan, Yoav; de-Bashan, Luz E

2016-06-01

During synthetic mutualistic interactions between the microalga Chlorella sorokiniana and the plant growth-promoting bacterium (PGPB) Azospirillum brasilense, mutual exchange of resources involved in producing and releasing the phytohormone indole-3-acetic acid (IAA) by the bacterium, using tryptophan and thiamine released by the microalga, were measured. Although increased activities of tryptophan synthase in C. sorokiniana and indole pyruvate decarboxylase (IPDC) in A. brasilense were observed, we could not detect tryptophan or IAA in the culture medium when both organisms were co-immobilized. This indicates that no extra tryptophan or IAA is produced, apart from the quantities required to sustain the interaction. Over-expression of the ipdC gene occurs at different incubation times: after 48 h, when A. brasilense was immobilized alone and grown in exudates of C. sorokiniana and at 96 h, when A. brasilense was co-immobilized with the microalga. When A. brasilense was cultured in exudates of C. sorokiniana, increased expression of the ipdC gene, corresponding increase in activity of IPDC encoded by the ipdC gene, and increase in IAA production were measured during the first 48 h of incubation. IAA production and release by A. brasilense was found only when tryptophan and thiamine were present in a synthetic growth medium (SGM). The absence of thiamine in SGM yielded no detectable IAA. In summary, this study demonstrates that C. sorokiniana can exude sufficient tryptophan and thiamine to allow IAA production by a PGPB during their interaction. Thiamine is essential for IAA production by A. brasilense and these three metabolites are part of a communication between the two microorganisms. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enhancement of the Rate of Pyrophosphate Hydrolysis by Nonenzymatic Catalysts and by Inorganic Pyrophosphatase*

PubMed Central

Stockbridge, Randy B.; Wolfenden, Richard

2011-01-01

To estimate the proficiency of inorganic pyrophosphatase as a catalyst, 31P NMR was used to determine rate constants and thermodynamics of activation for the spontaneous hydrolysis of inorganic pyrophosphate (PPi) in the presence and absence of Mg2+ at elevated temperatures. These values were compared with rate constants and activation parameters determined for the reaction catalyzed by Escherichia coli inorganic pyrophosphatase using isothermal titration calorimetry. At 25 °C and pH 8.5, the hydrolysis of MgPPi2− proceeds with a rate constant of 2.8 × 10−10 s−1, whereas E. coli pyrophosphatase was found to have a turnover number of 570 s−1 under the same conditions. The resulting rate enhancement (2 × 1012-fold) is achieved entirely by reducing the enthalpy of activation (ΔΔH‡ = −16.6 kcal/mol). The presence of Mg2+ ions or the transfer of the substrate from bulk water to dimethyl sulfoxide was found to increase the rate of pyrophosphate hydrolysis by as much as ∼106-fold. Transfer to dimethyl sulfoxide accelerated PPi hydrolysis by reducing the enthalpy of activation. Mg2+ increased the rate of PPi hydrolysis by both increasing the entropy of activation and reducing the enthalpy of activation. PMID:21460215

The relative hydrolytic reactivities of pyrophosphites and pyrophosphates.

PubMed

Mistry, Dharmit; Powles, Nicholas

2013-09-14

The pH-rate profiles for the hydrolysis of pyrophosphate (PP(V)) and pyrophosphite (PP(III), pyro-di-H-phosphonate) are a complex function of pH, reflecting the different ionic species and their relative reactivities. PP(III) is more reactive than PP(V) at all pHs and only PP(III) shows a hydroxide-ion reaction at high pH, so it is 10(10)-fold more reactive than PP(V) in 0.1 M NaOH. The pK(a2) of PP(III) ~0.44, so the dominant species at pH's > 1 is the di-anion PP(III)(2-). Although there is no observable (NMR or ITC) binding of Mg(2+) to the PP(III) di-anion there is a modest increase in the rate of hydrolysis of PP(III) by Mg(2+). PP(III) is neither a substrate nor an inhibitor of pyrophosphatase, the enzyme that efficiently catalyses the hydrolysis of PP(V).

Can diet-dependent factors help explain fish-to-fish variation in thiamine-dependent early mortality syndrome?

USGS Publications Warehouse

Brown, S.B.; Arts, M.T.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Honeyfield, D.C.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.; Hnath, J.G.

2005-01-01

To provide insight into the reasons why offspring of certain salmonine females exhibit early mortality syndrome (EMS) in the Great Lakes whereas others do not, we measured the egg concentrations of potential biochemical markers (stable isotopes of nitrogen and carbon, fatty acid signatures, and lipid-soluble carotenoids and vitamins) that are indicative of differing food web and trophic structure. To corroborate the presence of EMS, we also measured the egg content of thiamine vitamers. For all the stocks of coho salmon Oncorhynchus kisutch and Chinook salmon O. tshawytscha we studied, there was a very high correspondence between EMS and low concentrations of unphosphorylated thiamine in unfertilized eggs. For salmonine stocks in the Platte River, Thompson Creek, and the Swan River, Michigan, small but significant shifts occurred in measures of egg carotenoids, retinoids, ??15N depletion, and fatty acid profiles of fish producing normal offspring relative to those exhibiting EMS. Egg thiamine concentrations in Chinook salmon from the Little Manistee River, Michigan, in the low-EMS group were only marginally above the threshold for EMS induction. Along with this small thiamine differential, there was no evidence of differing food web or dietary factors between EMS-positive and normal Chinook salmon from the Little Manistee River. Further investigations are required to determine the potential dietary sources for the observed differences in biochemical markers between EMS-positive and normal fish. These findings are generally consistent with the hypothesis that a more diverse forage base may help to limit overall dietary content of species that contain thiaminase, such as alewives Alosa pseudoharengus, and may lead to improved embryonic survival for feral salmonids. ?? Copyright by the American Fisheries Society 2005.

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

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

Wang, Xin; Xu, Mei; Frank, Jacqueline A.

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stemmore » cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD

Determination of B-complex vitamins in pharmaceutical formulations by surface-enhanced Raman spectroscopy.

PubMed

Junior, Benedito Roberto Alvarenga; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Durango, Luis Guillermo Cuadrado; Forim, Moacir Rossi; Carneiro, Renato Lajarim

2018-01-05

The aim of this work was to quantify B-complex vitamins in pharmaceutical samples by surface enhanced Raman spectroscopy technique using gold colloid substrate. Synthesis of gold nanoparticles was performed according to an adapted Turkevich method. Initial essays were able to suggest the orientation of molecules on gold nanoparticles surface. Central Composite design was performed to obtain the highest SERS signal for nicotinamide and riboflavin. The evaluated parameters in the experimental design were volume of AuNPs, concentration of vitamins and sodium chloride concentration. The best condition for nicotinamide was NaCl 2.3×10 -3 molL -1 and 700μL of AuNPs colloid and this same condition showed to be adequate to quantify thiamine. The experimental design for riboflavin shows the best condition at NaCl 1.15×10 -2 molL -1 and 2.8mL of AuNPs colloid. It was possible to quantify thiamine and nicotinamide in presence of others vitamins and excipients in two solid multivitamin formulations using the standard addition procedure. The standard addition curve presented a R 2 higher than 0.96 for both nicotinamide and thiamine, at orders of magnitude 10 -7 and 10 -8 molL -1 , respectively. The nicotinamide content in a cosmetic gel sample was also quantified by direct analysis presenting R 2 0.98. The t-student test presented no significant difference regarding HPLC method. Despite the experimental design performed for riboflavin, it was not possible its quantification in the commercial samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyclic peptide unguisin A is an anion receptor with high affinity for phosphate and pyrophosphate.

PubMed

Daryl Ariawan, A; Webb, James E A; Howe, Ethan N W; Gale, Philip A; Thordarson, Pall; Hunter, Luke

2017-04-05

Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide. The biological function of this flexible macrocycle is obscure. Here we show that compound 1 lacks any detectable activity in antimicrobial growth inhibition assays, a result that runs contrary to a previous report. However, we find that 1 functions as a promiscuous host molecule in a variety of anion-binding interactions, with high affinity particularly for phosphate and pyrophosphate. We also show that a series of rigidified, backbone-fluorinated analogues of 1 displays altered affinity for chloride ions.

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

PubMed

Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

2003-05-01

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6 in rats.

PubMed

Gmoshinsky, I V; Vrzhesinskaya, O A; Shumakova, A A; Shipelin, V A; Kodentsova, V M; Khotimchenko, S A

2016-01-01

Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a food additive E551 in many enriched foods and food supplements. The aim of this study was to evaluate the effect of oral administration of SiO2 NPs on assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats. Amorphous SiO2 «Orisil-300 ®» was used with the size of the primary NPs 20-60 nm according to the electronic, atomic force microscopy and dynamic light scattering. The experiment was conducted on 8 groups of growing male Wistar rats (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14 and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through­out the experiment balanced semi-synthetic diet. Animals of the 2nd group received a diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and 8th groups -the same diet from the 1st to the 21th day, and then, before the closure of the experiment, the diet provided with the indicated B vitamins at 100% of normal level. From day 22 of experiment and until the end at day 29 the animals of the 3rd and 6th groups received deionized water (placebo) through intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2 dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day. Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter­mined by fluorimetric methods. It was found that rats in group 2 lagged in weight gain at day 21 significantly compared to group 1, and developed a marked deficiency of vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6 to 8 at day 29 par­tial recovery was achieved in vitamin status. Administration of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had no significant effect on any param­eters of vitamin status in comparison to group 3. However

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins.

PubMed

Allen, Lindsay H; Hampel, Daniela; Shahab-Ferdows, Setareh; York, Emily R; Adair, Linda S; Flax, Valerie L; Tegha, Gerald; Chasela, Charles S; Kamwendo, Debbie; Jamieson, Denise J; Bentley, Margaret E

2015-12-01

Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93-118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762. © 2015 American Society for Nutrition.

Three-dimensional structure of phosphoribosyl pyrophosphate synthetase from E. coli at 2.71 Å resolution

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

Timofeev, V. I., E-mail: inna@ns.crys.ras.ru, E-mail: tostars@mail.ru, E-mail: ugama@yandex.ru; Abramchik, Yu. A.; Zhukhlistova, N. E.

2016-01-15

Phosphoribosyl pyrophosphate synthetase from Escherichia coli was cloned, purified, and crystallized. Single crystals of the enzyme were grown under microgravity. The X-ray diffraction data set was collected at the Spring-8 synchrotron facility and used to determine the three-dimensional structure of the enzyme by the molecular-replacement method at 2.71 Å resolution. The active and regulatory sites in the molecule of E. coli phosphoribosyl pyrophosphate synthetase were revealed by comparison with the homologous protein from Bacillus subtilis, the structure of which was determined in a complex with functional ligands. The conformations of polypeptide-chain fragments surrounding and composing the active and regulatory sitesmore » were shown to be identical in both proteins.« less

Effects of forage family on apparent ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Seck, M; Beaudet, V; Kammes, K L; Linton, J A Voelker; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2016-03-01

Effects of forage family (legume vs. grass) on apparent ruminal synthesis (ARS) and postruminal supply of B vitamins were evaluated in 2 experiments. Diets containing either alfalfa (AL) or orchardgrass (OG) silages as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. Experiment 1 compared diets containing AL and OG [~23% forage neutral detergent fiber (NDF) and ~27% total NDF] offered to 8 cows in two 15-d treatment periods. Experiment 2 compared diets containing AL and OG (~25% forage NDF and ~30% total NDF) offered to 13 cows in two 18-d treatment periods. Thiamin, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were analyzed in feeds and duodenal digesta. Apparent ruminal synthesis was calculated as the duodenal flow of each vitamin minus its intake. Forage family affected B vitamin intakes, duodenal flow, and ARS. In both experiments, AL diets increased vitamin B6 and decreased folate intakes. In experiment 1, riboflavin and niacin intakes were greater with the OG diet, whereas in experiment 2 thiamin intake was greater but riboflavin intake was smaller with the OG diet. In spite of the low contribution of either silage to the dietary folate content, folate intake was greater with OG diets than AL due to the difference in soybean meal contribution between diets. Niacin and folate ARS were not affected by the forage family. Duodenal microbial nitrogen flow was positively correlated with ARS of riboflavin, niacin, vitamin B6, folates, and vitamin B12, but tended to be negatively correlated with thiamin ARS. Apparent ruminal synthesis of folates and vitamin B12 appear to be related to microbial biomass activity. Changes in nutrient composition of the diets likely affected the microbial population in the rumen and their B vitamin metabolism. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evaluation of a dental floss containing soluble pyrophosphate on calculus formation using a short-term clinical model.

PubMed

Kleber, C J; Putt, M S; Milleman, J L; Harris, M

1998-01-01

This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.

PLUTONIUM PURIFICATION PROCESS EMPLOYING THORIUM PYROPHOSPHATE CARRIER

DOEpatents

King, E.L.

1959-04-28

The separation and purification of plutonium from the radioactive elements of lower atomic weight is described. The process of this invention comprises forming a 0.5 to 2 M aqueous acidffc solution containing plutonium fons in the tetravalent state and elements with which it is normally contaminated in neutron irradiated uranium, treating the solution with a double thorium compound and a soluble pyrophosphate compound (Na/sub 4/P/sub 2/O/sub 7/) whereby a carrier precipitate of thorium A method is presented of reducing neptunium and - trite is advantageous since it destroys any hydrazine f so that they can be removed from solutions in which they are contained is described. In the carrier precipitation process for the separation of plutonium from uranium and fission products including zirconium and columbium, the precipitated blsmuth phosphate carries some zirconium, columbium, and uranium impurities. According to the invention such impurities can be complexed and removed by dissolving the contaminated carrier precipitate in 10M nitric acid, followed by addition of fluosilicic acid to about 1M, diluting the solution to about 1M in nitric acid, and then adding phosphoric acid to re-precipitate bismuth phosphate carrying plutonium.

Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings.

PubMed

Mozzillo, Enza; Melis, Daniela; Falco, Mariateresa; Fattorusso, Valentina; Taurisano, Roberta; Flanagan, Sarah E; Ellard, Sian; Franzese, Adriana

2013-08-01

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disease caused by loss of function mutations in the SLC19A2 gene. TRMA is characterized by anemia, deafness, and diabetes. In some cases, optic atrophy or more rarely retinitis pigmentosa is noted. We now report two sisters, the eldest of which presented to a different hospital during childhood with sensorineural deafness, which was treated with a hearing prosthesis, insulin requiring diabetes, retinitis pigmentosa, optic atrophy, and macrocytic anemia. These features initially suggested a clinical diagnosis of Wolfram syndrome (WS). Therapy with thiamine was initiated which resulted in the resolution of the anemia. The younger sister, who was affected with sensorineural deafness, was referred to our hospital for non-autoimmune diabetes. She was found to have macrocytosis and ocular abnormalities. Because a diagnosis of TRMA was suspected, therapy with insulin and thiamine was started. Sequencing analysis of the SLC19A2 gene identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in both sisters. Non-autoimmune diabetes associated with deafness and macrocytosis, without anemia, suggests a diagnosis of TRMA. Patients clinically diagnosed with WS with anemia and/or macrocytosis should be reevaluated for TRMA. © 2012 John Wiley & Sons A/S.

Biotin and Thiamine Responsive Basal Ganglia Disease--A vital differential diagnosis in infants with severe encephalopathy.

PubMed

Ygberg, Sofia; Naess, Karin; Eriksson, Mats; Stranneheim, Henrik; Lesko, Nicole; Barbaro, Michela; Wibom, Rolf; Wang, Chen; Wedell, Anna; Wickström, Ronny

2016-05-01

We report two siblings of Swedish origin with infantile Biotin and Thiamine Responsive Basal Ganglia Disease (BTRBG). Initial symptoms were in both cases lethargia, with reduced contact and poor feeding from the age of 5 weeks. Magnetic resonance imaging showed altered signal in the basal ganglia, along with grey and white matter abnormalities. The diagnosis BTRBG was not recognized in the first sibling who died at the age of 8 weeks. The second sibling was started on biotin and thiamine immediately upon development of symptoms, leading to clinical improvement and partial reversion of the magnetic resonance imaging findings. Genetic analysis of the SLC19A3 gene identified two mutations, c.74dupT and c.1403delA, carried in compound heterozygous form in both boys, each inherited from one parent. The first mutation has previously been described in children with BTRBG, and the second mutation is novel. Although the clinical picture in BTRGB is very severe it is also rather unspecific and the diagnosis may be missed. This report highlights the importance of considering biotin and thiamine treatment also in a European infant born to non-consanguineous parents, who presents with symptoms of acute/subacute encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

An exponential model equation for thiamin loss in irradiated ground pork as a function of dose and temperature of irradiation

NASA Astrophysics Data System (ADS)

Fox, J. B.; Thayer, D. W.; Phillips, J. G.

The effect of low dose γ-irradiation on the thiamin content of ground pork was studied in the range of 0-14 kGy at 2°C and at radiation doses from 0.5 to 7 kGy at temperatures -20, 10, 0, 10 and 20°C. The detailed study at 2°C showed that loss of thiamin was exponential down to 0kGy. An exponential expression was derived for the effect of radiation dose and temperature of irradiation on thiamin loss, and compared with a previously derived general linear expression. Both models were accurate depictions of the data, but the exponential expression showed a significant decrease in the rate of loss between 0 and -10°C. This is the range over which water in meat freezes, the decrease being due to the immobolization of reactive radiolytic products of water in ice crystals.

Vitamin B1-catalyzed acetoin formation from acetaldehyde: a key step for upgrading bioethanol to bulk C₄ chemicals.

PubMed

Lu, Ting; Li, Xiukai; Gu, Liuqun; Zhang, Yugen

2014-09-01

The production of bulk chemicals and fuels from renewable biobased feedstocks is of significant importance for the sustainability of human society. The production of ethanol from biomass has dramatically increased and bioethanol also holds considerable potential as a versatile building block for the chemical industry. Herein, we report a highly selective process for the conversion of ethanol to C4 bulk chemicals, such as 2,3-butanediol and butene, via a vitamin B1 (thiamine)-derived N-heterocyclic carbene (NHC)-catalyzed acetoin condensation as the key step to assemble two C2 acetaldehydes into a C4 product. The environmentally benign and cheap natural catalyst vitamin B1 demonstrates high selectivity (99%), high efficiency (97% yield), and high tolerance toward ethanol and water impurities in the acetoin reaction. The results enable a novel and efficient process for ethanol upgrading. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

B-vitamins, carotenoids and α-/γ-tocopherol in raw and roasted nuts.

PubMed

Stuetz, Wolfgang; Schlörmann, Wiebke; Glei, Michael

2017-04-15

The concentrations of B-vitamins, carotenoids and tocopherols in nuts may differ between species and might be influenced by roasting. Thiamine, riboflavin, pyridoxine, lutein, zeaxanthin, β-carotene and α-/γ-tocopherol were determined in different varieties of raw and roasted nuts using HPLC (fluorescence/UV-vis detection). The analysis revealed remarkable concentrations of thiamine and pyridoxine in pistachios (57%, 79% of the recommended daily intake/100g (RDI), respectively) and riboflavin in almonds (119% of the RDI). Pistachios were rich in lutein/zeaxanthin and contained highest β-carotene levels among nuts. Almonds and hazelnuts were abundant in α-tocopherol (>4-fold the RDI for tocopherol equivalents) while pistachios and walnuts were rich in γ-tocopherol. Roasting had a diminishing effect on thiamine, carotenoids and tocopherols especially in almonds and walnuts. Nuts could make a valuable contribution to a healthy diet in regard to B-vitamins, lutein/zeaxanthin and tocopherols. A reduction in micronutrient content by roasting is reliant on the nut variety and specific micronutrient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+.

PubMed

Panov, A; Scarpa, A

1996-01-16

The activity of alpha-ketoglutarate dehydrogenase complex (KGDHC), an important enzyme regulating several metabolic pathways, could be regulated by changes in the environment within the mitochondrial matrix. It has been postulated that the activity of this and other dehydrogenases in vivo could be modulated by changes in the intramitochondrial concentrations of Ca2+ or Mg2+. Using a purified alpha-ketoglutarate dehydrogenase from pig hearts, the effect of Ca2+ and/or Mg2+ on the enzyme activity was investigated. Either Ca2+ or Mg2+ increased enzyme activity, and the effects were additive if the concentrations of free divalent cations were below 0.1 and 1 mM for Ca2+ and Mg2+, respectively. In the presence of 1 mM alpha-ketoglutarate and other cofactors, the KM for Mg2+ was 25 microM and less than 1 microM for Ca2+. The KM for alpha-ketoglutarate was a function of the divalent cation(s) present: 4 +/- 1.1 mM in the absence of Ca2+, with or without Mg2+; 2.2 mM in the presence of 1.8 microM Ca2+ alone; and 0.3 mM in the presence of both Ca2+ and Mg2+. Mg2+ increased KGDHC activity only in the presence of thiamine pyrophosphate (TPP) indicating that KGDHC requires both TPP and Mg2+ for enzyme's maximal activity. The affinity of KGDHC for NAD+ is significantly changed by either Mg2+ or Ca2+. The conclusions are that changes in both Ca2+ and Mg2+, in concentrations possibly occurring within mitochondria, could control KGDHC activity and that thiamine pyrophosphate is required for maximal enzyme activity.

Label-free electrical detection of pyrophosphate generated from DNA polymerase reactions on field-effect devices.

PubMed

Credo, Grace M; Su, Xing; Wu, Kai; Elibol, Oguz H; Liu, David J; Reddy, Bobby; Tsai, Ta-Wei; Dorvel, Brian R; Daniels, Jonathan S; Bashir, Rashid; Varma, Madoo

2012-03-21

We introduce a label-free approach for sensing polymerase reactions on deoxyribonucleic acid (DNA) using a chelator-modified silicon-on-insulator field-effect transistor (SOI-FET) that exhibits selective and reversible electrical response to pyrophosphate anions. The chemical modification of the sensor surface was designed to include rolling-circle amplification (RCA) DNA colonies for locally enhanced pyrophosphate (PPi) signal generation and sensors with immobilized chelators for capture and surface-sensitive detection of diffusible reaction by-products. While detecting arrays of enzymatic base incorporation reactions is typically accomplished using optical fluorescence or chemiluminescence techniques, our results suggest that it is possible to develop scalable and portable PPi-specific sensors and platforms for broad biomedical applications such as DNA sequencing and microbe detection using surface-sensitive electrical readout techniques.

Structure of Leishmania major Methionyl-tRNA Synthetase in Complex with Intermediate Products Methionyladenylate and Pyrophosphate

PubMed Central

Larson, Eric T.; Kim, Jessica E.; Zucker, Frank H.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Verlinde, Christophe L.M.J.; Fan, Erkang; Buckner, Frederick S.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G.J.

2011-01-01

Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of E. coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNAMet complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme. PMID:21144880

Molecular cloning and expression of Chimonanthus praecox farnesyl pyrophosphate synthase gene and its possible involvement in the biosynthesis of floral volatile sesquiterpenoids.

PubMed

Xiang, Lin; Zhao, Kaige; Chen, Longqing

2010-01-01

Farnesyl pyrophosphate (FPP) synthase catalyzes the biosynthesis of FPP, which is the precursors of sesquiterpenoids such as floral scent volatiles, from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). cDNA encoding wintersweet (Chimonanthus praecox L.) FPP synthase was isolated by the RT-PCR and RACE methods. The deduced amino acid sequence showed a high identity to plant FPP synthases. Expression of the gene in Escherichia coli yielded FPPS activity that catalyzed the synthesis of FPP as a main product. Tissue-specific and developmental analyses of the mRNA levels of CpFPPS and volatile sesquiterpenoids levels in C. praecox flowers revealed that the FPPS may play a regulatory role in floral volatile sesquiterpenoids of wintersweet. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Technetium-99m Pyrophosphate: Comparison of ED50 for Tetany and Acidosis with Acute LD500

DTIC Science & Technology

electrocardiogram and chemical analysis revealed that the hypocalcemic effect occurs at a much lower dosage than for the LD50. Polyphosphate was found to be more...toxic by the LD50 analysis than pyrophosphate. It is emphasized that the hypocalcemic toxic effects should be the determining factor in deciding what...to 1 with regard to the first signs of hypocalcemia by electrocardiographic measurements (i.e., 2 mg/kg). On this basis an injection of no more than 1 mg/kg is recommended to maintain a safety factor of around 10 to 1.

Pyrophosphate as substrate for alkaline phosphatase activity: A convenient flow-injection chemiluminescence assay.

PubMed

Zhang, Qingfeng; Zhang, Cuiyun; Yang, Meiding; Yu, Donghong; Yu, Cong

2017-11-01

A sensitive and convenient flow-injection chemiluminescence (FI-CL) turn-on assay for alkaline phosphatase (ALP) activity without any label and synthesis is developed. Cu 2+ can catalyze the luminol-H 2 O 2 CL reaction. Pyrophosphate (PPi) can chelate Cu 2+ and therefore the Cu 2+ -mediated luminol-H 2 O 2 CL reaction is inhibited. The addition of ALP can catalyze the hydrolysis of PPi into phosphate ions, Cu 2+ is released and the chemiluminescence recovers. A detection limit of 1 mU/mL ALP is obtained. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular cloning and expression of Hedychium coronarium farnesyl pyrophosphate synthase gene and its possible involvement in the biosynthesis of floral and wounding/herbivory induced leaf volatile sesquiterpenoids.

PubMed

Lan, Jian-bin; Yu, Rang-cai; Yu, Yun-yi; Fan, Yan-ping

2013-04-15

Farnesyl pyrophosphate synthase (FPPS EC 2.5.1.10) catalyzes the production of farnesyl pyrophosphate (FPP), which is a key precursor for many sesquiterpenoids such as floral scent and defense volatiles against herbivore attack. Here we report a new full-length cDNA encoding farnesyl diphosphate synthase from Hedychium coronarium. The open reading frame for full-length HcFPPS encodes a protein of 356 amino acids, which is 1068 nucleotides long with calculated molecular mass of 40.7 kDa. Phylogenetic tree analysis indicates that HcFPPS belongs to the plant FPPS super-family and has strong relationship with FPPS from Musa acuminata. Expression of the HcFPPS gene in Escherichia coli yielded FPPS activity. Tissue-specific and developmental analyses of the HcFPPS mRNA and corresponding volatile sesquiterpenoid levels in H. coronarium flowers revealed that the HcFPPS might play a regulatory role in floral volatile sesquiterpenoid biosynthesis. The emission of the FPP-derived volatile terpenoid correlates with strong expression of HcFPPS induced by mechanical wounding and Udaspes folus-damage in leaves, which suggests that HcFPPS may have an important ecological function in H. coronarium vegetative organ. Copyright © 2013 Elsevier B.V. All rights reserved.

High-concentrate diets based on forages harvested at different maturity stages affect ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Kammes, K L; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2017-04-01

Effects of plant maturity on apparent ruminal synthesis and post-ruminal supply of B vitamins were evaluated in two feeding trials. Diets containing alfalfa (Trial 1) or orchardgrass (Trial 2) silages harvested either (1) early cut, less mature (EC) or (2) late cut, more mature (LC) as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. In Trial 1, conducted with 16 cows (569±43 kg of empty BW (ruminal content removed) and 43.7±8.6 kg/day of 3.5% fat-corrected milk yield; mean±SD) in two 17-day treatment periods, both diets provided ~22% forage NDF and 27% total NDF, and the forage-to-concentrate ratios were 53 : 47 and 42 : 58 for EC and LC, respectively. In Trial 2, conducted with 13 cows (588±55 kg of empty BW and 43.7±7.7 kg/day of 3.5% fat-corrected milk yield; mean±SD) in two 18-day treatment periods, both diets provided ~25% forage NDF and 31% total NDF; the forage-to-concentrate ratios were 58 : 42 and 46 : 54 for EC and LC, respectively. Thiamin, riboflavin, niacin, vitamin B6, folates and vitamin B12 were measured in feed and duodenal content. Apparent ruminal synthesis was calculated as the duodenal flow minus the intake. Diets based on EC alfalfa decreased the amounts of thiamin, niacin and folates reaching the duodenum, whereas diets based on EC orchardgrass increased riboflavin duodenal flow. Daily apparent ruminal synthesis of thiamin, riboflavin, niacin and vitamin B6 were correlated negatively with their intake, suggesting a microbial regulation of their concentration in the rumen. Vitamin B12 apparent ruminal synthesis was correlated negatively with total volatile fatty acids concentration, but positively with ruminal pH and microbial N duodenal flow.

Predictive model for growth of Clostridium perfringens during cooling of cooked beef supplemented with NaCl, sodium nitrite and sodium pyrophosphate

USDA-ARS?s Scientific Manuscript database

This paper presents a model for predicting relative growth of C. perfringens in ground beef products at different percentages of salt (0%, 1%, 2% and 3%) and nitrite (0 and 200 ppm). Included in the experiments were different levels of sodium pyrophosphate (SPP). The results of the experiments indic...

Magnetite nanoparticle-induced fluorescence quenching of adenosine triphosphate-BODIPY Conjugates: application to adenosine triphosphate and pyrophosphate sensing.

PubMed

Yu, Cheng-Ju; Wu, Su-Mei; Tseng, Wei-Lung

2013-09-17

We report that magnetite nanoparticles (Fe3O4 NPs) act as an efficient quencher for boron dipyrromethene-conjugated adenosine 5'-triphosphate (BODIPY-ATP) that is highly fluorescent in bulk solution. BODIPY-ATP molecules attached to the surface of Fe3O4 NPs through the coordination between the triphosphate group of BODIPY-ATP and Fe(3+)/Fe(2+) on the NP surface. The formed complexes induced an apparent reduction in the BODIPY-ATP fluorescence resulting from an oxidative-photoinduced electron transfer (PET) from the BODIPY-ATP excited state to an unfilled d shell of Fe(3+)/Fe(2+) on the NP surface. A comparison of the Stern-Volmer quenching constant between Fe(3+) and Fe(2+) suggests that Fe(3+) on the NP surface dominantly controls this quenching process. The efficiency for Fe3O4 NP-induced fluorescence quenching of the BODIPY-ATP was enhanced by increasing the concentration of Fe3O4 NPs and lowering the pH of the solution to below 6.0. We found that pyrophosphate and ATP compete with BODIPY-ATP for binding to Fe3O4 NPs. Thus, we amplified BODIPY-ATP fluorescence in the presence of increasing the pyrophosphate and ATP concentration; the detection limits at a signal-to-noise ratio of 3 for pyrophosphate and ATP were determined to be 7 and 30 nM, respectively. The Fe3O4 NP-based competitive binding assay detected ATP and pyrophosphate in only 5 min. The selectivity of this assay for ATP over metal ions, amino acids, and adenosine analogues is particularly high. The practicality of using the developed method to determine ATP in a single drop of blood is also validated.

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus , a New Twist on ATP Formation

DOE PAGES

James, Kimberly L.; Ríos-Hernández, Luis A.; Wofford, Neil Q.; ...

2016-08-16

Syntrophus aciditrophicusis a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation byS. aciditrophicus. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome ofS. aciditrophicusleaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show thatS. aciditrophicususes AMP-forming, acetyl-CoA synthetase (Acs1)more » for ATP synthesis from acetyl-CoA.acs1mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, ofS. aciditrophicusgrown in pure culture and coculture. Cell extracts ofS. aciditrophicushad low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified fromS. aciditrophicusand recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) inS. aciditrophicuscells support the operation of Acs1 in the acetate-forming direction. Thus,S. aciditrophicushas a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase. We find bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA.Syntrophus aciditrophicusapparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus , a New Twist on ATP Formation

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

James, Kimberly L.; Ríos-Hernández, Luis A.; Wofford, Neil Q.

Syntrophus aciditrophicusis a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation byS. aciditrophicus. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome ofS. aciditrophicusleaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show thatS. aciditrophicususes AMP-forming, acetyl-CoA synthetase (Acs1)more » for ATP synthesis from acetyl-CoA.acs1mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, ofS. aciditrophicusgrown in pure culture and coculture. Cell extracts ofS. aciditrophicushad low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified fromS. aciditrophicusand recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) inS. aciditrophicuscells support the operation of Acs1 in the acetate-forming direction. Thus,S. aciditrophicushas a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase. We find bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA.Syntrophus aciditrophicusapparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as

A Stilbenoid-Specific Prenyltransferase Utilizes Dimethylallyl Pyrophosphate from the Plastidic Terpenoid Pathway1[OPEN

PubMed Central

2016-01-01

Prenylated stilbenoids synthesized in some legumes exhibit plant pathogen defense properties and pharmacological activities with potential benefits to human health. Despite their importance, the biosynthetic pathways of these compounds remain to be elucidated. Peanut (Arachis hypogaea) hairy root cultures produce a diverse array of prenylated stilbenoids upon treatment with elicitors. Using metabolic inhibitors of the plastidic and cytosolic isoprenoid biosynthetic pathways, we demonstrated that the prenyl moiety on the prenylated stilbenoids derives from a plastidic pathway. We further characterized, to our knowledge for the first time, a membrane-bound stilbenoid-specific prenyltransferase activity from the microsomal fraction of peanut hairy roots. This microsomal fraction-derived resveratrol 4-dimethylallyl transferase utilizes 3,3-dimethylallyl pyrophosphate as a prenyl donor and prenylates resveratrol to form arachidin-2. It also prenylates pinosylvin to chiricanine A and piceatannol to arachidin-5, a prenylated stilbenoid identified, to our knowledge, for the first time in this study. This prenyltransferase exhibits strict substrate specificity for stilbenoids and does not prenylate flavanone, flavone, or isoflavone backbones, even though it shares several common features with flavonoid-specific prenyltransferases. PMID:27356974

Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

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

Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

1981-04-01

Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

Iron and Manganese Pyrophosphates as Cathodes for Lithium-Ion Batteries

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

Zhou, Hui; Upreti, Shailesh; Chernova, Natasha A.

2015-10-15

The mixed-metal phases, (Li{sub 2}Mn{sub 1-y}Fe{sub y}P{sub 2}O{sub 7}, 0 {le} y {le} 1), were synthesized using a 'wet method', and found to form a solid solution in the P2{sub 1}/a space group. Both thermogravimetric analysis and magnetic susceptibility measurements confirm the 2+ oxidation state for both the Mn and Fe. The electrochemical capacity improves as the Fe concentration increases, as do the intensities of the redox peaks of the cyclic voltammogram, indicating higher lithium-ion diffusivity in the iron phase. The two Li{sup +} ions in the three-dimensional tunnel structure of the pyrophosphate phase allows for the cycling of moremore » than one lithium per redox center. Cyclic voltammograms show a second oxidation peak at 5 V and 5.3 V, indicative of the extraction of the second lithium ion, in agreement with ab initio computation predictions. Thus, electrochemical capacities exceeding 200 Ah/kg may be achieved if a stable electrolyte is found.« less

Thalamic Proteome Changes and Behavioral Impairments in Thiamine-deficient Rats.

PubMed

Nunes, Polliana Toledo; Gómez-Mendoza, Diana Paola; Rezende, Cristiana Perdigão; Figueiredo, Henrique César Pereira; Ribeiro, Angela Maria

2018-06-09

Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. Following 15 days of recovery, all rats were submitted to the spatial cognitive tasks in the Morris Water Maze (MWM). The results show that the PTD rats exhibited deficits during the learning process, which was reverted by repeated training. However, despite the spatial cognitive recovery, some protein changes were not reversible. The proteomic analysis, using label-free quantification, revealed deregulation of 183 thalamic proteins. Using bioinformatic tools, these proteins were categorized according to Gene Ontology functional annotation and metabolic pathways. We show that a severe TD affects proteins involved in different biological processes, such as, oxidative stress, neurotransmitter synthesis and synaptic vesicle cycle. These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults.

PubMed

Howe, Caitlin G; Li, Zhigang; Zens, Michael S; Palys, Thomas; Chen, Yu; Channon, Jacqueline Y; Karagas, Margaret R; Farzan, Shohreh F

2017-12-01

Background: Arsenic exposure has been associated with an increased risk of cardiovascular disease (CVD). Growing evidence suggests that B vitamins facilitate arsenic metabolism and may protect against arsenic toxicity. However, to our knowledge, few studies have evaluated this in US populations. Objective: Our objective was to examine whether higher B vitamin intake is associated with enhanced arsenic metabolism and lower concentrations of preclinical markers of CVD among New Hampshire adults. Methods: We used weighted quantile sum (WQS) regression to evaluate the collective impact of 6 dietary B vitamins (thiamin, riboflavin, folate, niacin, and vitamins B-6 and B-12) on 1 ) the proportion of arsenic metabolites in urine and 2 ) 6 CVD-related markers [including urinary 15-F 2t -isoprostane (15-F 2t -IsoP)] among 418 participants (26-75 y of age) from the New Hampshire Health Study. Contributions of arsenic metabolites to B vitamin-CVD marker associations were also explored in structural equation models. Results: In WQS models, the weighted sum of B vitamin intakes from food sources was inversely associated with the proportion of monomethyl arsenic species in urine (uMMA) (β: -1.03; 95% CI: -1.91, -0.15; P = 0.02). Thiamin and vitamins B-6 and B-12 contributed the most to this association, whereas riboflavin had a negligible effect. Higher overall B vitamin intake was also inversely associated with 15-F 2t -IsoP (β: -0.21; 95% CI: -0.32, -0.11; P < 0.01), with equal contributions from the 6 B vitamins, which was partially explained by differences in the proportion of uMMA (indirect effect β: -0.01; 95% CI: -0.04, -0.00). Conclusions: Among New Hampshire adults, higher intakes of certain B vitamins (particularly thiamin and vitamins B-6 and B-12 from food sources) may reduce the proportion of uMMA, an intermediate of arsenic metabolism that has been associated with an increased risk of CVD. Higher overall B vitamin intake may also reduce urinary 15-F 2t -IsoP, a

Live-Cell Pyrophosphate Imaging by in Situ Hot-Spot Generation.

PubMed

Li, Mingmin; Li, Jin; Di, Huixia; Liu, Huiqiao; Liu, Dingbin

2017-03-21

Controlling the electromagnetic hot-spot generation is essential for surface-enhanced Raman scattering (SERS) assays. Current hot-spot-based SERS assays have been extensively studied in solutions or on substrates. However, probing biospecies by controlling the hot-spot assembly in living systems has not been demonstrated thus far. Herein, we report a background-free SERS probe for imaging pyrophosphate (PPi), a biochemically significant anion, in living cells. Intracellular PPi is able to induce the nanoparticle dimerization, thus creating an intense electromagnetic hot spot and dramatically enhancing the signal of the Raman reporters residing in the hot spot. More impressively, the reporter we used in this study provides a strong and sharp single peak in the cellular Raman-silent region (1800-2800 cm -1 ), thus eliminating the possible background interference. This strategy could be readily extended to detect other biomarkers by only replacing the recognition ligands.

[Effect of heat transfer in the packages on the stability of thiamine nitrate under uncontrolled temperature conditions].

PubMed

Nakamura, Toru; Yamaji, Takayuki; Takayama, Kozo

2013-01-01

To accurately predict the stability of thiamine nitrate as a model drug in pharmaceutical products under uncontrolled temperature conditions, the average reaction rate constant was determined, taking into account the heat transfer from the atmosphere to the product. The stability tests of thiamine nitrate in the three packages with different heat transfers were performed under non-isothermal conditions. The stability data observed were compared with the predictions based on a newly developed method, showing that the stability was well predicted by the method involving the heat transfer. By contrast, there were some deviations observed from the predicted data, without considering heat transfer in the packages with low heat transfer. The above-mentioned result clearly shows that heat transfer should be considered to ensure accurate prediction of the stability of commercial pharmaceutical products under non-isothermal atmospheres.

Determination of B-complex vitamins in pharmaceutical formulations by surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Junior, Benedito Roberto Alvarenga; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Durango, Luis Guillermo Cuadrado; Forim, Moacir Rossi; Carneiro, Renato Lajarim

2018-01-01

The aim of this work was to quantify B-complex vitamins in pharmaceutical samples by surface enhanced Raman spectroscopy technique using gold colloid substrate. Synthesis of gold nanoparticles was performed according to an adapted Turkevich method. Initial essays were able to suggest the orientation of molecules on gold nanoparticles surface. Central Composite design was performed to obtain the highest SERS signal for nicotinamide and riboflavin. The evaluated parameters in the experimental design were volume of AuNPs, concentration of vitamins and sodium chloride concentration. The best condition for nicotinamide was NaCl 2.3 × 10- 3 mol L- 1 and 700 μL of AuNPs colloid and this same condition showed to be adequate to quantify thiamine. The experimental design for riboflavin shows the best condition at NaCl 1.15 × 10- 2 mol L- 1 and 2.8 mL of AuNPs colloid. It was possible to quantify thiamine and nicotinamide in presence of others vitamins and excipients in two solid multivitamin formulations using the standard addition procedure. The standard addition curve presented a R2 higher than 0.96 for both nicotinamide and thiamine, at orders of magnitude 10- 7 and 10- 8 mol L- 1, respectively. The nicotinamide content in a cosmetic gel sample was also quantified by direct analysis presenting R2 0.98. The t-student test presented no significant difference regarding HPLC method. Despite the experimental design performed for riboflavin, it was not possible its quantification in the commercial samples.

B vitamins in the nervous system.

PubMed

Bender, D A

1984-01-01

The coenzyme functions of the B vitamins in intermediatry metabolism are well established; nevertheless, for none of them is it possible to determine precisely the connection between the biochemical lesions associated with deficiency and the neurological consequences. Although there is convincing evidence of a neurospecific role for thiamin and other B vitamins, in no case has this role been adequately described. Similarly, the neurochemical sequelae of intoxication by massive amounts of vitamins (so-called mega-vitamin therapy or orthomolecular medicine) remain largely unexplained.

Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies.

PubMed

Fraser, Jamie L; Vanderver, Adeline; Yang, Sandra; Chang, Taeun; Cramp, Laura; Vezina, Gilbert; Lichter-Konecki, Uta; Cusmano-Ozog, Kristina P; Smpokou, Patroula; Chapman, Kimberly A; Zand, Dina J

2014-01-01

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation which resulted in an improved clinical course.

Effect of thiamine hydrochloride on the redox reactions of iron at pyrite surface. [Fourth quarterly techical progress report, September 1990--November 1990

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

Pesic, B.; Oliver, D.J.

1990-12-31

The present investigation is a part of our studies on the electro chemical aspects of pyrite bioleaching involving Thiobacillus ferrooxidans. Previously (1,2) we have examined the effect of T. ferrooxidans and their metabolic products on the redox reactions of Fe{sup 2+}/Fe{sup 3+} couple at the pyrite surface. Results obtained suggest that beyond 1. 5 days during their growth in a batch fermenter, the bacteria and their metabolic products completely cover the pyrite surface and shut down all electron transfer across the electrode-solution interface. In addition, it has been observed that the bacteria serve as the nucleation site for jarosite formation,more » which is found detrimental to bioleaching. In the present work we have focussed on the effect of the presence of vitamins on the redox chemistry of iron. Our examination of the effect of the presence of thiamine hydrochloride in the redox behavior of Fe{sup 2+}/Fe{sup 3+} at the pyrite surface has revealed that thiamine hydrochloride does not undergo chemical interaction with ferrous or ferric iron. However, it may adsorb onto the pyrite surface causing polarization of the pyrite electrode.« less

Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis

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

Wizenberg, T.A.; Muz, J.; Sohn, Y.H.

1982-04-01

Ten consecutive patients with tissue-proven amyloidosis, seven of whom presented with congestive heart failure, were found to exhibit intense diffuse uptake of technetium-99m-pyrophosphate (Tc-99m-PYP) on cardiac radionuclide imaging. The patients exhibited echocardiographic and systolic time interval abnormalities suggesting combined restrictive and congestive cardiomyopathic changes. On M-mode echocardiograms, there was symmetrically increased thickness of the interventricular septum and left ventricular (LV) posterior wall in diastole (10 of 10), decreased fractional shortening of the LV minor axis diameter in systole (eight of nine), and decreased percent thickening of the LV minor axis diameter in systole (eight of nine) and LV posterior wallmore » (10 of 10) in systole. Three patients demonstrated enlarged LV end-diastolic diameter. All 10 patients had abnormal PEP/LVET and eight had shortened LVETI. When combined with noninvasive tests of LV performance, positive myocardial pyrophosphate (PYP) scanning provides a new and useful adjunct in the diagnosis of amyloid heart disease.« less

In Vitro Selection for Small-Molecule-Triggered Strand Displacement and Riboswitch Activity.

PubMed

Martini, Laura; Meyer, Adam J; Ellefson, Jared W; Milligan, John N; Forlin, Michele; Ellington, Andrew D; Mansy, Sheref S

2015-10-16

An in vitro selection method for ligand-responsive RNA sensors was developed that exploited strand displacement reactions. The RNA library was based on the thiamine pyrophosphate (TPP) riboswitch, and RNA sequences capable of hybridizing to a target duplex DNA in a TPP regulated manner were identified. After three rounds of selection, RNA molecules that mediated a strand exchange reaction upon TPP binding were enriched. The enriched sequences also showed riboswitch activity. Our results demonstrated that small-molecule-responsive nucleic acid sensors can be selected to control the activity of target nucleic acid circuitry.

Thiamine Deprivation Produces a Liver ATP Deficit and Metabolic and Genomic Effects in Mice: Findings Are Parallel to Those of Biotin Deficiency and Have Implications for Energy Disorders.

PubMed

Hernandez-Vazquez, Alain de J; Garcia-Sanchez, Josue Andres; Moreno-Arriola, Elizabeth; Salvador-Adriano, Ana; Ortega-Cuellar, Daniel; Velazquez-Arellano, Antonio

2016-01-01

Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine. They are similar to the ones we have previously found in biotin deficiency, another ATP generation cofactor. Here we show that thiamine deficiency substantially reduced the energy state in the liver and activated the energy sensor AMP-activated kinase. With this vitamin deficiency, several metabolic parameters changed: blood glucose was diminished and serum lactate was increased, but insulin, triglycerides, and cholesterol, as well as liver glycogen, were reduced. These results indicate a severe change in the energy status of the whole organism. Our findings were associated with modified hepatic levels of the mRNAs of several carbon metabolism genes: a reduction of transcripts for liver glucokinase and fatty acid synthase and augmentation of those for carnitine palmitoyl transferase 1 and phosphoenolpyruvate carboxykinase as markers for glycolysis, fatty acid synthesis, beta-oxidation, and gluconeogenesis, respectively. Glucose tolerance was initially increased, suggesting augmented insulin sensitivity, as we had found in biotin deficiency; however, in the case of thiamine, it was diminished from the 3rd week on, when the deficient animals became undernourished, and paralleled the changes in AKT and mTOR, 2 main proteins in the insulin signaling pathway. Since many of the metabolic and gene expression effects on mice deprived of thiamine are similar to those in biotin deficiency

Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

PubMed

Anholt, H; Himsworth, C; Britton, A

2016-07-01

Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat. © The Author(s) 2016.

Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo.

PubMed

Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten; Mayer, Dirk; Collins, Amy M; Luong, Richard; Pfefferbaum, Adolf

2016-07-01

Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE). This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment. Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls. These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

DNA damage during glycation of lysine by methylglyoxal: assessment of vitamins in preventing damage.

PubMed

Suji, G; Sivakami, S

2007-11-01

Amino acids react with methylglyoxal to form advanced glycation end products. This reaction is known to produce free radicals. In this study, cleavage to plasmid DNA was induced by the glycation of lysine with methylglyoxal in the presence of iron(III). This system was found to produce superoxide as well as hydroxyl radicals. The abilities of various vitamins to prevent damage to plasmid DNA were evaluated. Pyridoxal-5-phosphate showed maximum protection, while pyridoxamine showed no protection. The protective abilities could be directly correlated to inhibition of production of hydroxyl and superoxide radicals. Pyridoxal-5-phosphate exhibited low radical scavenging ability as evaluated by its TEAC, but showed maximum protection probably by interfering in free radical production. Pyridoxamine did not inhibit free radical production. Thiamine and thiamine pyrophosphate, both showed protective effects albeit to different extents. Tetrahydrofolic acid showed better antioxidant activity than folic acid but was found to damage DNA by itself probably by superoxide generation.

Electron density reactivity indexes of the tautomeric/ionization forms of thiamin diphosphate.

PubMed

Jaña, Gonzalo A; Delgado, Eduardo J

2013-09-01

The generation of the highly reactive ylide in thiamin diphosphate catalysis is analyzed in terms of the nucleophilicity of key atoms, by means of density functional calculations at X3LYP/6-31++G(d,p) level of theory. The Fukui functions of all tautomeric/ionization forms are calculated in order to assess their reactivity. The results allow to conclude that the highly conserved glutamic residue does not protonate the N1' atom of the pyrimidyl ring, but it participates in a strong hydrogen bonding, stabilizing the eventual negative charge on the nitrogen, in all forms involved in the ylide generation. This condition provides the necessary reactivity on key atoms, N4' and C2, to carry out the formation of the ylide required to initiate the catalytic cycle of ThDP-dependent enzymes. This study represents a new approach for the ylide formation in ThDP catalysis.

Control of plant phosphate homeostasis by inositol pyrophosphates and the SPX domain.

PubMed

Jung, Ji-Yul; Ried, Martina K; Hothorn, Michael; Poirier, Yves

2018-02-01

Proteins containing a SPX domain are involved in phosphate (Pi) homeostasis, including Pi transport and adaptation to Pi deficiency. The SPX domain harbors a basic surface binding Pi at low affinity and inositol pyrophosphates (PP-InsPs) at high affinity. Genetic and biochemical studies revealed that PP-InsPs serve as ligands for the SPX domain. Residues in the PHO1 SPX domain involved in PP-InsPs binding are critical for its Pi export activity, and the interaction between SPX proteins and the PHR1 transcription factor, which results in PHR1 inactivation, is promoted by PP-InsPs. Changes in PP-InsPs levels in response to Pi deficiency may thus contribute to the adaptation of plants to stress via the modulation of the activity of SPX-containing proteins and their interactors. Modulating PP-InsP levels or the affinity/specificity of the SPX domain for PP-InsP could potentially be used to engineer crops to maintain high yield under reduced Pi fertilizer input. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measurement of serum, liver, and brain cytokine induction, thiamine levels, and hepatopathology in rats exposed to a 4-day alcohol binge protocol.

PubMed

Zahr, Natalie M; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

2010-11-01

 In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation. This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho. Ten of 18 wild-type male Wistar rats (~322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ~315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines. There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior

Powder XRD and dielectric studies of gel grown calcium pyrophosphate crystals

NASA Astrophysics Data System (ADS)

Parekh, Bharat; Parikh, Ketan; Joshi, Mihir

2013-06-01

Formation of calcium pyrophosphate dihydrate (CPPD) crystals in soft tissues such as cartilage, meniscus and synovial tissue leads to CPPD deposition diseases. The appearance of these crystals in the synovial fluid can give rise to an acute arthritic attack with pain and inflammation of the joints, a condition called pseudo-gout. The growth of CPP crystals has been carried out, in the present study, using the single diffusion gel growth technique, which can broadly mimic in vitro the condition in soft tissues. The crystals were characterized by different techniques. The FTIR study revealed the presence of various functional groups. Powder XRD study was also carried out to verify the crystal structure. The dielectric study was carried out at room temperature by applying field of different frequency from 500 Hz to 1 MHz. The dielectric constant, dielectric loss and a.c. resistivity decreased as frequency increased, whereas the a.c. conductivity increased as frequency increased.

Pyrophosphate-Dependent Fructose-6-Phosphate 1-Phosphotransferase Induction and Attenuation of Hsp Gene Expression during Endosperm Modification in Quality Protein Maize1[C][W][OA

PubMed Central

Guo, Xiaomei; Ronhovde, Kyla; Yuan, Lingling; Yao, Bo; Soundararajan, Madhavan P.; Elthon, Thomas; Zhang, Chi; Holding, David R.

2012-01-01

Quality Protein Maize (QPM) is a hard-endosperm version of the high-lysine opaque2 (o2) maize (Zea mays) mutant, but the genes involved in modification of the soft o2 endosperm are largely unknown. Pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase (PFP) catalyzes the ATP-independent conversion of fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis. We found a large increase in transcript and protein levels of the α-regulatory subunit of PFP (PFPα) in QPM endosperm. In vitro enzyme assays showed a significant increase in forward PFP activity in developing endosperm extracts of QPM relative to the wild type and o2. An expressed retrogene version of PFPα of unknown function that was not up-regulated in QPM was also identified. The elevated expression levels of a number of ATP-requiring heat shock proteins (Hsps) in o2 endosperm are ameliorated in QPM. PFPα is also coinduced with Hsps in maize roots in response to heat, cold, and the unfolded protein response stresses. We propose that reduced ATP availability resulting from the generalized Hsp response in addition to the reduction of pyruvate, orthophosphate dikinase activity in o2 endosperm is compensated in part by increased PFP activity in QPM. PMID:22158678

Synthesis of β-Calcium Pyrophosphate by sol-gel method

NASA Astrophysics Data System (ADS)

Windarti, T.; Taslimah; Haris, A.; Astuti, Y.; Darmawan, A.

2017-02-01

Beta calcium pyrophosphate [β-CPP, β-Ca2P2O7] can be used as bone graft extender in posterolateral lumbar fusion. In this research, β-CPP was synthesized by sol-gel method using phosphorus pentaoxide [P2O5] and calcium nitrate tetrahydrate [Ca(NO3)2.4H2O] as phosphorus and calcium precursors. The reaction was carried out in ethanol medium with Ca/P ratio of 1.67. After 21 hours of reaction and 20 hours of drying at 80°C, white powder of amorphous calcium phosphate (ACP) was produced. Transformation of ACP to β-CPP was undertaken by firring at 400-800°C for 8 hours. Transformations of amorphous to microcrystalline, semicrystalline and crystalline structures occur at 400, 600 and 800°C, respectively. The β-CPP with the crystallite size of 61.71 nm, Ca/P ratio of 0.89 and Ca/O ratio of 0.21 was achieved by firing at 800°C. Morphology changes due to firing in which irregular shape of β-CPP at 400° changed to regular cuboid at 600 °C and above.

CRYSTALLINE INORGANIC PYROPHOSPHATASE ISOLATED FROM BAKER'S YEAST

PubMed Central

Kunitz, M.

1952-01-01

Crystalline inorganic pyrophosphatase has been isolated from baker's yeast. The crystalline enzyme is a protein of the albumin type with an isoelectric point near pH 4.8. Its molecular weight is of the order of 100,000. It contains about 5 per cent tyrosine and 3.5 per cent tryptophane. It is most stable at pH 6.8. The new crystalline protein acts as a specific catalyst for the hydrolysis of inorganic pyrophosphate into orthophosphate ions. It does not catalyze the hydrolysis of the pyrophosphate radical of such organic esters as adenosine di- and triphosphate, or thiamine pyrophosphate. Crystalline pyrophosphatase requires the presence of Mg, Co, or Mn ions as activators. These ions are antagonized by calcium ions. Mg is also antagonized by Co or Mn ions. The rate of the enzymatic hydrolysis of inorganic pyrophosphate is proportional to the concentration of enzyme and is a function of pH, temperature, concentration of substrate, and concentration of activating ion. The approximate conditions for optimum rate are: 40°C. and pH 7.0 at a concentration of 3 to 4 x 10–3 M Na4P2O7 and an equivalent concentration of magnesium salt. The enzymatic hydrolysis of Na4P2O7 or K4P2O7 proceeds to completion and is irreversible under the conditions at which hydrolysis is occurring. Details are given of the method of isolation of the crystalline enzyme. PMID:14898026

Modelling the effect of pH, sodium chloride and sodium pyrophosphate on the thermal resistance of Escherichia coli O157:H7 in ground beef

USDA-ARS?s Scientific Manuscript database

A fractional factorial design was used to assess the combined effects of four internal temperatures (55.0, 57.5, 60.0 and 62.5C) and five concentrations of sodium chloride (NaCl) (0.0, 1.5, 3.0, 4.5 and 6.0 wt/wt%) and sodium pyrophosphate (SPP) (0.0, 0.1, 0.15, 0.2 and 0.3 wt/wt%) on the heat resis...

Osteoblast response to zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate

PubMed Central

Whited, Bryce M.; Skrtic, Drago; Love, Brian J.

2006-01-01

Calcium phosphate bioceramics, such as hydroxyapatite, have long been used as bone substitutes because of their proven biocompatibility and bone binding properties in vivo. Recently, a zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate (Zr-ACP) has been synthesized, which is more soluble than hydroxyapatite and allows for controlled release of calcium and phosphate ions. These ions have been postulated to increase osteoblast differentiation and mineralization in vitro. The focus of this work is to elucidate the physicochemical properties of Zr-ACP and to measure cell response to Zr-ACP in vitro using a MC3T3-E1 mouse calvarial-derived osteoprogenitor cell line. Cells were cultured in osteogenic medium and mineral was added to culture at different stages in cell maturation. Culture in the presence of Zr-ACP showed significant increases in cell proliferation, alkaline phosphatase activity (ALP), and osteopontin (OPN) synthesis, whereas collagen synthesis was unaffected. In addition, calcium and phosphate ion concentrations and medium pH were found to transiently increase with the addition of Zr-ACP, and are hypothesized to be responsible for the osteogenic effect of Zr-ACP. PMID:16278876

Simultaneous Determination of Metamizole, Thiamin and Pyridoxin Using UV-Spectroscopy in Combination with Multivariate Calibration

PubMed Central

Chotimah, Chusnul; Sudjadi; Riyanto, Sugeng; Rohman, Abdul

2015-01-01

Purpose: Analysis of drugs in multicomponent system officially is carried out using chromatographic technique, however, this technique is too laborious and involving sophisticated instrument. Therefore, UV-VIS spectrophotometry coupled with multivariate calibration of partial least square (PLS) for quantitative analysis of metamizole, thiamin and pyridoxin is developed in the presence of cyanocobalamine without any separation step. Methods: The calibration and validation samples are prepared. The calibration model is prepared by developing a series of sample mixture consisting these drugs in certain proportion. Cross validation of calibration sample using leave one out technique is used to identify the smaller set of components that provide the greatest predictive ability. The evaluation of calibration model was based on the coefficient of determination (R2) and root mean square error of calibration (RMSEC). Results: The results showed that the coefficient of determination (R2) for the relationship between actual values and predicted values for all studied drugs was higher than 0.99 indicating good accuracy. The RMSEC values obtained were relatively low, indicating good precision. The accuracy and presision results of developed method showed no significant difference compared to those obtained by official method of HPLC. Conclusion: The developed method (UV-VIS spectrophotometry in combination with PLS) was succesfully used for analysis of metamizole, thiamin and pyridoxin in tablet dosage form. PMID:26819934

A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct.

PubMed

Arjunan, Palaniappa; Sax, Martin; Brunskill, Andrew; Chandrasekhar, Krishnamoorthy; Nemeria, Natalia; Zhang, Sheng; Jordan, Frank; Furey, William

2006-06-02

The crystal structure of the E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) has been determined with phosphonolactylthiamin diphosphate (PLThDP) in its active site. PLThDP serves as a structural and electrostatic analogue of the natural intermediate alpha-lactylthiamin diphosphate (LThDP), in which the carboxylate from the natural substrate pyruvate is replaced by a phosphonate group. This represents the first example of an experimentally determined, three-dimensional structure of a thiamin diphosphate (ThDP)-dependent enzyme containing a covalently bound, pre-decarboxylation reaction intermediate analogue and should serve as a model for the corresponding intermediates in other ThDP-dependent decarboxylases. Regarding the PDHc-specific reaction, the presence of PLThDP induces large scale conformational changes in the enzyme. In conjunction with the E1-PLThDP and E1-ThDP structures, analysis of a H407A E1-PLThDP variant structure shows that an interaction between His-407 and PLThDP is essential for stabilization of two loop regions in the active site that are otherwise disordered in the absence of intermediate analogue. This ordering completes formation of the active site and creates a new ordered surface likely involved in interactions with the lipoyl domains of E2s within the PDHc complex. The tetrahedral intermediate analogue is tightly held in the active site through direct hydrogen bonds to residues His-407, Tyr-599, and His-640 and reveals a new, enzyme-induced, strain-related feature that appears to aid in the decarboxylation process. This feature is almost certainly present in all ThDP-dependent decarboxylases; thus its inclusion in our understanding of general thiamin catalysis is important.

Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation.

PubMed

Sun, Chengjun; Pei, Zhou; Zhang, Miaoying; Sun, Bijun; Yang, Lin; Zhao, Zhuhui; Cheng, Ruoqian; Luo, Feihong

2018-01-01

Solute carrier family 19 member 2 (SLC19A2) gene deficiency is one of the causes of permanent neonatal diabetes mellitus (PNDM) and can be effectively managed by thiamine supplementation. Herein we report on a male patient with a novel SLC19A2 mutation and summarize the clinical characteristics of patients with SLC19A2 deficiency. The genetic diagnosis of the patient with PNDM was made by sequencing and quantitative polymerase chain reaction. The clinical characteristics of PNDM were summarized on the basis of a systematic review of the literature. The patient with PNDM had c.848G>A (p.W283X) homozygous mutation in SLC19A2. His father had a wild-type SLC19A2 (c.848G) and his mother was c.848G/A heterozygous. The patient and his father both had a diploid genotype (c.848A/A and c.848G/G). After oral thiamine administration, the patient's fasting C-peptide levels increased gradually, and there was a marked decrease in insulin requirements. A search of the literature revealed that thiamine treatment was effective and improved diabetes in 63% of patients with SLC19A2 deficiency. A novel SLC19A2 mutation (c.848G>A; p.W283X) was identified, which was most likely inherited as segmental uniparental isodisomy. Insulin insufficiency in PNDM caused by SLC19A2 deficiency can be corrected by thiamine supplementation. The differential diagnosis of SLC19A2 deficiency should be considered in children with PNDM accompanied by anemia or hearing defects to allow for early treatment. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

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

Forman, M.B.; Sandler, M.P.; Sacks, G.A.

1983-03-01

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Benzaldehyde lyase, a novel thiamine PPi-requiring enzyme, from Pseudomonas fluorescens biovar I.

PubMed Central

González, B; Vicuña, R

1989-01-01

Pseudomonas fluorescens biovar I can grow on benzoin as the sole carbon and energy source. This ability is due to benzaldehyde lyase, a new type of enzyme that irreversibly cleaves the acyloin linkage of benzoin, producing two molecules of benzaldehyde. Benzaldehyde lyase was purified 70-fold and found to require catalytic amounts of thiamine PPi (TPP) and a divalent cation as cofactors. Optimal activity was obtained with a 1.0 mM concentration of Mn2+, Mg2+, or Ca2+. Gel permeation chromatography indicated a native molecular weight of 80,000, whereas the enzyme migrated in sodium dodecyl sulfate-containing polyacrylamide gels as a single polypeptide with a molecular weight of 53,000. Benzaldehyde lyase is highly specific; of a variety of structurally related compounds tested, only benzoin and anisoin (4,4'-dimethoxybenzoin) acted as substrates, their apparent Kms being 9.0 x 10(-3) and 3.25 x 10(-2) mM, respectively. A catalytic mechanism for the enzyme is proposed. Images PMID:2496105

Zn2+-dependent surface behavior of diacylglycerol pyrophosphate and its mixtures with phosphatidic acid at different pHs

PubMed Central

Villasuso, Ana L.; Wilke, Natalia; Maggio, Bruno; Machado, Estela

2014-01-01

Diacylglycerol pyrophosphate (DGPP) is a minor lipid that attenuates the phosphatidic acid (PA) signal, and also DGPP itself would be a signaling lipid. Diacylglycerol pyrophosphate is an anionic phospholipid with a pyrophosphate group attached to diacylglycerol that was shown to respond to changes of pH, thus affecting the surface organization of DGPP and their interaction with PA. In this work, we have investigated how the presence of Zn2+ modulates the surface organization of DGPP and its interaction with PA at acidic and basic pHs. Both lipids formed expanded monolayers at pHs 5 and 8. At pH 5, monolayers formed by DGPP became stiffer when Zn2+was added to the subphase, while the surface potential decreased. At this pH, Zn2+ induced a phase transition from an expanded to a condensed-phase state in monolayers formed by PA. Conversely, at pH 8 the effects induced by the presence of Zn2+ on the surface behaviors of the pure lipids were smaller. Thus, the interaction of the bivalent cation with both lipids was modulated by pH and by the ionization state of the polar head groups. Mixed monolayers of PA and DGPP showed a non-ideal behavior and were not affected by the presence of Zn2+ at pH 8. This could be explained considering that when mixed, the lipids formed a closely packed monolayer that could not be further modified by the cation. Our results indicate that DGPP and PA exhibit expanded- and condensed-phase states depending on pH, on the proportion of each lipid in the film and on the presence of Zn2+. This may have implications for a possible role of DGPP as a signaling lipid molecule. PMID:25120554

Effect of pyrophosphate ions on the conversion of calcium-lithium-borate glass to hydroxyapatite in aqueous phosphate solution.

PubMed

Fu, Hailuo; Rahaman, Mohamed N; Day, Delbert E; Huang, Wenhai

2010-10-01

The conversion of glass to a hydroxyapatite (HA) material in an aqueous phosphate solution is used as an indication of the bioactive potential of the glass, as well as a low temperature route for preparing biologically useful materials. In this work, the effect of varying concentrations of pyrophosphate ions in the phosphate solution on the conversion of a calcium-lithium-borate glass to HA was investigated. Particles of the glass (150-355 μm) were immersed for up to 28 days in 0.25 M K(2)HPO(4) solution containing 0-0.1 M K(4)P(2)O(7). The kinetics of degradation of the glass particles and their conversion to HA were monitored by measuring the weight loss of the particles and the ionic concentration of the solution. The structure and composition of the conversion products were analyzed using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. For K(4)P(2)O(7) concentrations of up to 0.01 M, the glass particles converted to HA, but the time for complete conversion increased from 2 days (no K(4)P(2)O(7)) to 10 days (0.01 M K(4)P(2)O(7)). When the K(4)P(2)O(7) concentration was increased to 0.1 M, the product consisted of an amorphous calcium phosphate material, which eventually crystallized to a pyrophosphate product (predominantly K(2)CaP(2)O(7) and Ca(2)P(2)O(7)). The consequences of the results for the formation of HA materials and devices by the glass conversion route are discussed.

Effect of pyrophosphate ions on the conversion of calcium–lithium–borate glass to hydroxyapatite in aqueous phosphate solution

PubMed Central

Fu, Hailuo; Day, Delbert E.; Huang, Wenhai

2010-01-01

The conversion of glass to a hydroxyapatite (HA) material in an aqueous phosphate solution is used as an indication of the bioactive potential of the glass, as well as a low temperature route for preparing biologically useful materials. In this work, the effect of varying concentrations of pyrophosphate ions in the phosphate solution on the conversion of a calcium–lithium–borate glass to HA was investigated. Particles of the glass (150–355 µm) were immersed for up to 28 days in 0.25 M K2HPO4 solution containing 0–0.1 M K4P2O7. The kinetics of degradation of the glass particles and their conversion to HA were monitored by measuring the weight loss of the particles and the ionic concentration of the solution. The structure and composition of the conversion products were analyzed using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. For K4P2O7 concentrations of up to 0.01 M, the glass particles converted to HA, but the time for complete conversion increased from 2 days (no K4P2O7) to 10 days (0.01 M K4P2O7). When the K4P2O7 concentration was increased to 0.1 M, the product consisted of an amorphous calcium phosphate material, which eventually crystallized to a pyrophosphate product (predominantly K2CaP2O7 and Ca2P2O7). The consequences of the results for the formation of HA materials and devices by the glass conversion route are discussed. PMID:20680413

Reduced activities of thiamine-dependent and cytochrome c oxidase enzymes in cerebral cortex of cattle affected by sulfur-induced polioencephalomalacia