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Formate metabolism is altered in riboflavin‐deficient rats
Author(s) -
MacMillan Luke,
Lamarre Simon,
Andrivon Estelle,
Dickie Charlotte,
Brosnan Margaret E.,
Brosnan John T.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.246.1
Subject(s) - riboflavin , formate , methylenetetrahydrofolate reductase , homocysteine , cofactor , metabolism , chemistry , reductase , biochemistry , glutathione , medicine , glutathione reductase , endocrinology , enzyme , biology , glutathione peroxidase , genotype , gene , catalysis
Riboflavin can play an important role in one‐carbon metabolism, particularly as its active forms, FAD and FMN, are used as cofactors in both the production and utilization of formate. Rats were fed either a riboflavin‐replete or a riboflavin‐deficient diet for 13 days at which point blood and tissue samples were taken. Riboflavin deficiency was assessed by the Erythrocyte Glutathione Reductase activation coefficient (EGRac). Total plasma homocysteine (Hcy), hepatic S‐adenosylmethionine (SAM), and S‐adenosylhomocysteine (SAH) concentrations were analyzed by HPLC. Hepatic methylenetetrahydrofolate reductase (MTHFR) was assessed by means of enzyme activity and immunoblot. Plasma formate was analyzed by GC‐MS. EGRac confirmed riboflavin deficiency. Plasma Hcy was elevated in the deficient animals. Hepatic SAM was lower in the deficient animals; there was no difference in SAH. MTHFR was found to be markedly reduced in the deficient group; plasma formate concentration was decreased by about 20%. The increased plasma Hcy and reduced hepatic SAM indicate an impairment in re‐methylation. The decreased plasma formate levels coupled with the defective remethylation suggest that the flavin‐dependent formate production may be decreased. This will be further examined by means of isotopic experiments to measure the endogenous rates of formate production. Grant Funding Source : Canadian Institutes of Health Research & Research Development Corporation of Newfoundland and Labrador