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Results for “THIAMINE PYROPHOSPHATE”

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At least 91 records · Page 5Linked to original sources

PubMed1983

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

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.

Chorismic Acid↗

PubMed1985

Changes in erythrocyte transketolase activity and the thiamine pyrophosphate effect during storage of blood.

Whole blood and washed erythrocytes from nutritionally normal and abnormal elderly patients were stored at room temperature, 4 degrees C and -20 degrees C for up to 14 days. In both groups, and under all storage conditions, the erythrocyte transketolase (ETK) activity and the thiamine pyrophosphate (TPP) effect decreased with time of storage. The ETK activity for specimens stored at -20 degrees C decreased significantly by day 14 (P less than 0.05). The TPP effect in specimens stored at -20 degrees C decreased significantly in the nutritionally abnormal group at 4 days (P less than 0.05) and in the nutritionally normal group by day 14 (P less than 0.05). These significant changes in ETK activity and TPP effect with storage can lead to misleading interpretation of thiamine nutritional status.

Aged↗

PubMed2006

Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand.

Riboswitches are untranslated regions of messenger RNA, which adopt alternate structures depending on the binding of specific metabolites. Such conformational switching regulates the expression of proteins involved in the biosynthesis of riboswitch substrates. Here, we present the 2.9 angstrom-resolution crystal structure of the eukaryotic Arabidopsis thaliana thiamine pyrophosphate (TPP)-specific riboswitch in complex with its natural ligand. The riboswitch specifically recognizes the TPP via conserved residues located within two highly distorted parallel "sensor" helices. The structure provides the basis for understanding the reorganization of the riboswitch fold upon TPP binding and explains the mechanism of resistance to the antibiotic pyrithiamine.

3' Untranslated Regions↗

PubMed1984

Direct physical evidence for stabilization of branched-chain alpha-ketoacid dehydrogenase by thiamin pyrophosphate.

Branched-chain alpha-ketoacid dehydrogenase is a multienzyme complex composed of four subunits. The 46,500-dalton protein is a subunit of the decarboxylase component, which is selectively digested by chymotrypsin. Two peptides of apparent mol. wts. of 36,000 and 15,000 result with loss of enzyme activity. When the complex is saturated with thiamin pyrophosphate and ketoacid substrate, digestion by chymotrypsin does not occur. These data provide direct physical evidence for the stabilization of the complex by the presence of the vitamin B1-derived cofactor.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed2002

Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate.

The genome of Saccharomyces cerevisiae contains 35 members of a family of transport proteins that, with a single exception, are found in the inner membranes of mitochondria. The transport functions of the 15 biochemically identified mitochondrial carriers are concerned with shuttling substrates, biosynthetic intermediates and cofactors across the inner membrane. Here the identification of the mitochondrial carrier for the essential cofactor thiamine pyrophosphate (ThPP) is described. The protein has been overexpressed in bacteria, reconstituted into phospholipid vesicles and identified by its transport properties. In confirmation of its identity, cells lacking the gene for this carrier had reduced levels of ThPP in their mitochondria, and decreased activity of acetolactate synthase, a ThPP-requiring enzyme found in the organellar matrix. They also required thiamine for growth on fermentative carbon sources.

Carbon↗

PubMed1988

Differential reactivity in the processing of [p-(halomethyl)benzoyl] formates by benzoylformate decarboxylase, a thiamin pyrophosphate dependent enzyme.

A series of [p-(halomethyl)benzoyl]formates have been investigated as substrates for benzoylformate decarboxylase. These analogues vary from acting as normal substrates to acting as potent competitive inhibitors. The fluoro analogue is a substrate with Km (190 microM) and turnover number (20 s-1) similar to those of benzoylformate (Km = 340 microM; 81 s-1). The bromo analogue is a competitive inhibitor (Ki = 0.3 microM) and exhibits processing to eliminate bromide and form (p-methylbenzoyl)thiamin pyrophosphate. This modified cofactor hydrolyzes to form the p-methylbenzoate in quantitative yield. The chloro analogue [Km(app) = 21 microM] partitions between these two pathways such that 0.6% of the analogue ultimately forms p-methylbenzoate. These data are consistent with the interpretation that the leaving group potential of the halogen determines the enzymic fate of the analogue and that the potent inhibition observed for the bromo analogue is due to covalent modification of the cofactor.

Alcohol Dehydrogenase↗

PubMed1996

Thiamine pyrophosphate and pyridoxamine inhibit the formation of antigenic advanced glycation end-products: comparison with aminoguanidine.

Nonenzymatic glycation of proteins by glucose leading to the formation of toxic and immunogenic advanced glycation end products (AGEs) may be a major contributor to the pathological manifestations of diabetes mellitus, aging, and, possibly, neurodegenerative diseases such as Alzheimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by various vitamin B1 and B6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compounds may have novel therapeutic potential in preventing vascular complications of diabetes. An unexpected finding was that aminoguanidine inhibited the late kinetic stages of glycation much more weakly than the early phase.

Animals↗

PubMed2006

Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.

SLC25A19 mutations cause Amish lethal microcephaly (MCPHA), which markedly retards brain development and leads to alpha-ketoglutaric aciduria. Previous data suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleotide transporter. We generated a knockout mouse model of Slc25a19. These animals had 100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day 10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a yolk sac erythropoietic failure, and elevated alpha-ketoglutarate in the amniotic fluid. We found that these animals have normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels, suggesting that transport of these molecules is not the primary role of SLC25A19. We identified thiamine pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through homology searching and confirmed it by using transport assays of the recombinant reconstituted protein. The mitochondria of Slc25a19(-/-) and MCPHA cells have undetectable and markedly reduced ThPP content, respectively. The reduction of ThPP levels causes dysfunction of the alpha-ketoglutarate dehydrogenase complex, which explains the high levels of this organic acid in MCPHA and suggests that mitochondrial ThPP transport is important for CNS development.

Anemia↗

PubMed1952