title: Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate restriction in young women.
abstract: 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.
authors.affiliation: Food Science & Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville 32611-0370, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Davis
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Quinlivan
authors.forename: Karla P
authors.initials: KP
authors.lastname: Shelnutt
authors.forename: Haifa
authors.initials: H
authors.lastname: Ghandour
authors.forename: Antonieta
authors.initials: A
authors.lastname: Capdevila
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Coats
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Barry
authors.initials: B
authors.lastname: Shane
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Bailey
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000201:enzymology*; D008401:Gas Chromatography-Mass Spectrometry; D006710:Homocysteine / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012694:Serine / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006710:Homocysteine; D012694:Serine; D005492:Folic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007930:Leucine