title: Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?
abstract: 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.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3X9.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brosnan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3X9.
authors.forename: Luke
authors.initials: L
authors.lastname: MacMillan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3X9.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Stevens
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3X9 jbrosnan@mun.ca.
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D004734:Energy Metabolism; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D009751:Nutritional Requirements; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012436:S-Adenosylmethionine / Q000378:metabolism; D012694:Serine / Q000008:administration & dosage / Q000096:biosynthesis; D000099295:Formyltetrahydrofolate Dehydrogenase
chemical_list: D000444:Aldehyde Dehydrogenase; D000596:Amino Acids; D005492:Folic Acid; D007527:Isoenzymes; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012436:S-Adenosylmethionine; D012694:Serine; D000099295:Formyltetrahydrofolate Dehydrogenase
keywords: NADPH; S-adenosylmethionine; folate; formate; glycine metabolism; serine neogenesis