title: In vivo kinetics of formate metabolism in folate-deficient and folate-replete rats.
abstract: It is now established that the mitochondrial production of formate is a major process in the endogenous generation of folate-linked one-carbon groups. We have developed an in vivo approach involving the constant infusion of [(13)C]formate until isotopic steady state is attained to measure the rate of endogenous formate production in rats fed on either a folate-replete or folate-deficient diet. Formate was produced at a rate of 76 μmol·h(-1)·100 g of body weight(-1) in the folate-replete rats, and this was decreased by 44% in folate-deficient rats. This decreased formate production was confirmed in isolated rat liver mitochondria where formate production from serine, the principal precursor of one-carbon groups, was decreased by 85%, although formate production from sarcosine and dimethylglycine (choline metabolites) was significantly increased. We attribute this unexpected result to the demonstrated production of formaldehyde by sarcosine dehydrogenase and dimethylglycine dehydrogenase from their respective substrates in the absence of tetrahydrofolate and subsequent formation of formate by formaldehyde dehydrogenase. Comparison of formate production with the ingestion of dietary formate precursors (serine, glycine, tryptophan, histidine, methionine, and choline) showed that ∼75% of these precursors were converted to formate, indicating that formate is a significant, although underappreciated end product of choline and amino acid oxidation. Ingestion of a high protein diet did not result in increased production of formate, suggesting a regulation of the conversion of these precursors at the mitochondrial level to formate.
authors.affiliation: From the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Morrow
authors.affiliation: From the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: MacMillan
authors.affiliation: Departement de Biologie, Universite de Moncton, Moncton, New Brunswick E1A 3E9, Canada, and.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Lamarre
authors.affiliation: From the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Young
authors.affiliation: Nutrition Research Division, Health Canada, Ottawa K1A 0K9, Ontario, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: MacFarlane
authors.affiliation: From the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brosnan
authors.affiliation: From the Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada, jbrosnan@mun.ca.
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
mesh_terms: D000818:Animals; D002794:Choline / Q000737:chemistry; D050893:Dimethylglycine Dehydrogenase; D005492:Folic Acid / Q000737:chemistry*; D005494:Folic Acid Deficiency / Q000378:metabolism*; D005557:Formaldehyde / Q000737:chemistry; D005561:Formates / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D050892:Sarcosine Dehydrogenase / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013763:Tetrahydrofolates / Q000737:chemistry
chemical_list: D005561:Formates; D013763:Tetrahydrofolates; C030544:formic acid; D005557:Formaldehyde; C030371:5,6,7,8-tetrahydrofolic acid; D012694:Serine; D006639:Histidine; D005492:Folic Acid; D008715:Methionine; D050892:Sarcosine Dehydrogenase; D050893:Dimethylglycine Dehydrogenase; D002794:Choline; D010100:Oxygen; D005998:Glycine
keywords: Amino Acid; Choline; Methionine; Mitochondria; One-carbon Metabolism; Serine; Tetrahydrofolate; Vitamin