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Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?

Journal

BIOCHEMICAL JOURNAL
Volume 472, Issue -, Pages 135-146

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BJ20150837

Keywords

folate; formate; glycine metabolism; NADPH; S-adenosylmethionine; serine neogenesis

Funding

  1. Canadian Institutes of Health Research
  2. Research Development Corporation of Newfoundland and Labrador [5404.1433.101]
  3. Research Development Corporation of Newfoundland and Labrador [CIHR] [MOP-142321]
  4. School of Graduate Studies, Memorial University

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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.

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