Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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Many coenzymes are vitamins that are assimilated in mammals into their active form from precursors obtained from the diet. They are often both rare and reactive rendering the likelihood low that the cell uses a collision-based strategy for their delivery to dependent enzymes. In humans, there are only two known B12 or cobalamin-dependent enzymes: methionine synthase and methylmalonyl-CoA mutase. However, the pathway for intracellular assimilation and utilization of this cofactor is complex as revealed by careful clinical analyses of fibroblasts from patients with disorders of cobalamin metabolism. In the recent past, six of the eight human genes involved in the B12 pathway have been identified and these have yielded important insights into their roles. The recent literature on the encoded proteins is reviewed, and a model for intracellular B12 trafficking is proposed in which B12 is escorted to its target proteins in the cytoplasmic and mitochondrial compartments in complex with chaperones, thereby averting problems of dilution and adventitious side reactions.
ACS Chem Biol 2006 Apr 25
PMID:B12 trafficking in mammals: A for coenzyme escort service. 1716 62

In this study, we have investigated the transcriptome of Ralstonia eutropha H16 during cultivation with gluconate in presence of 3,3'-thiodipropionic acid (TDP) or 3,3'-dithiodipropionic acid (DTDP) during biosynthesis of poly(3-hydroxybutyrate-co-3-mercaptopropionate). Genome-wide transcriptome analyses revealed several genes which were upregulated during cultivation in presence of the above-mentioned compounds. Obtained data strongly suggest that two ABC-type transport system and three probable extracytoplasmic solute receptors mediate the uptake of TDP and DTDP, respectively. In addition, genes encoding the hydrolase S-adenosylhomocysteinase AhcY and the thiol-disulfide interchange proteins DsbA, DsbD, and FrnE were upregulated during cultivation on DTDP and, in case of AhcY and FrnE, on TDP as well. It is assumed that the corresponding enzymes are involved in the cleavage of TDP and DTDP. Several genes of the fatty acid metabolism exhibited increased expression levels: genes encoding two acetyltransferases, a predicted acyltransferase, the acetoacetyl-CoA reductase phaB3, an enoyl-CoA hydratase as well as an acyl dehydratase, an acetyl-CoA synthetase, two acyl-CoA dehydrogenases, the methylmalonyl-CoA mutase encoded by sbm1 and sbm2 and phaY1 were detected. Furthermore, ORF H16_A0217 encoding a hypothetical protein and exhibiting 54% amino acids identical to an acyl-CoA thioesterase from Saccharomonospora viridis was found to be highly upregulated. As the 2-methylcitrate synthase PrpC exhibited a three- to fourfold increased activity in cells grown in presence of TDP or DTDP as compared to gluconate, metabolization of the cleavage products 3MP and 3-hydroxypropionate to propionyl-CoA is proposed.
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PMID:Investigations on the microbial catabolism of the organic sulfur compounds TDP and DTDP in Ralstonia eutropha H16 employing DNA microarrays. 2092 76