title: Riboflavin Deficiency in Rats Decreases de novo Formate Production but Does Not Affect Plasma Formate Concentration.
abstract: Background:The one-carbon metabolism pathway is highly dependent on a number of B vitamins in order to provide one-carbon units for purine and thymidylate biosynthesis as well as homocysteine remethylation. Previous studies have examined folate and vitamin B-12 deficiency and their effects on formate metabolism; as of yet, to our knowledge, no studies on the effects of riboflavin deficiency on formate metabolism have been published.Objective:Our objective was to determine the effects of riboflavin deficiency on formate metabolism.Methods:Weanling male rats were randomly assigned either to control, riboflavin-replete (RR) or to experimental, riboflavin-deficient (RD) versions of the AIN-93G diet for 13 d, at which time a constant infusion of [13C]-formate was carried out to ascertain the effects of deficiency on formate production. Gas chromatography-mass spectrometry was used to measure plasma formate concentration and [13C]-formate enrichment. HPLC, LC-mass spectrometry (MS)/MS, and enzymatic assays were used for the measurement of one-carbon precursors and other metabolites.Results:RD rats had significantly lower rates of formate production (15%) as well as significantly reduced hepatic methylenetetrahydrofolate reductase activity (69%) and protein concentration (54%) compared with RR rats. There was no difference in plasma formate concentrations between the groups. Plasma serine, a potential one-carbon precursor, was significantly higher in RD rats (467 ± 73 μM) than in RR rats (368 ± 52 μM).Conclusions:Although deficiencies in folate and vitamin B-12 lead to major changes in plasma formate concentrations, riboflavin deficiency results in no significant difference; this disagrees with the prediction of a published mathematical model. Our observation of a lower rate of formate production is consistent with a role for flavoproteins in this process.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: MacMillan
authors.affiliation: Department of Biology, University of Moncton, Moncton, New Brunswick, Canada; and.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Lamarre
authors.affiliation: Department of Agricultural, Food and Nutritional Sciences, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Robin P
authors.initials: RP
authors.lastname: daSilva
authors.affiliation: Department of Agricultural, Food and Nutritional Sciences, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: René L
authors.initials: RL
authors.lastname: Jacobs
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brosnan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada; jbrosnan@mun.ca.
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D002247:Carbon Isotopes; D004032:Diet / Q000662:veterinary; D005561:Formates / Q000097:blood / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012257:Riboflavin Deficiency / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D005561:Formates; C030544:formic acid
keywords: S-adenosylmethionine; folate; glycine; methylenetetrahydrofolate reductase; one-carbon metabolism; riboflavin; serine