Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate restriction in young women.

Davis SR, Quinlivan EP, Shelnutt KP, Ghandour H, Capdevila A, Coats BS, Wagner C, Shane B, Selhub J, Bailey LB, Shuster JJ, Stacpoole PW, Gregory JF
J Nutr. 2005 135 (5): 1045-50

PMID: 15867279 · DOI:10.1093/jn/135.5.1045

The effects of folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism on the kinetics of homocysteine metabolism are unclear. We measured the effects of dietary folate restriction on the kinetics of homocysteine remethylation and synthesis in healthy women (20-30 y old) with the MTHFR 677 C/C or T/T genotypes (n = 9/genotype) using i.v. primed, constant infusions of [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(3)]leucine before and after 7 wk of dietary folate restriction (115 mug dietary folate equivalents/d). Dietary folate restriction significantly reduced folate status ( approximately 65% reduction in serum folate) in both genotypes. Total remethylation flux was not affected by dietary folate restriction, the MTHFR 677C-->T polymorphism, or their combination. However, the percentage of remethylation from serine was reduced approximately 15% (P = 0.031) by folate restriction in C/C subjects. Further, homocysteine synthesis rates of T/T subjects and folate-restricted C/C subjects were twice that of C/C subjects at baseline. In conclusion, elevated homocysteine synthesis is a cause of mild hyperhomocysteinemia in women with marginal folate status, particularly those with the MTHFR 677 T/T genotype.

MeSH Terms (14)

Adult Amino Acids Female Folic Acid Folic Acid Deficiency Gas Chromatography-Mass Spectrometry Homocysteine Humans Leucine Methionine Methylation Methylenetetrahydrofolate Reductase (NADPH2) Polymorphism, Single Nucleotide Serine

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