One-carbon metabolism is usually represented as having three canonical functions: purine synthesis, thymidylate synthesis and methylation reactions. There is however a fourth major function: the metabolism of some amino acids (serine, glycine, tryptophan and histidine), as well as choline. These substrates can provide cells with more one-carbon groups than they need for these three canonical functions. Therefore, there must be mechanisms for the disposal of these one-carbon groups (when in excess) which maintain the complement of these groups required for the canonical functions. The key enzyme for these mechanisms is 10-formyl-THF (tetrahydrofolate) dehydrogenase (both mitochondrial and cytoplasmic isoforms) which oxidizes the formyl group to CO2 with the attendant reduction of NADP+ to NADPH and release of THF. In addition to oxidizing the excess of these compounds, this process can reduce substantial quantities of NADP+ to NADPH.
Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?
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Margaret E. Brosnan, Luke MacMillan, Jennifer R. Stevens, John T. Brosnan; Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?. Biochem J 1 December 2015; 472 (2): 135–146. doi: https://doi.org/10.1042/BJ20150837
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