Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate restriction in young women.
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.
Davis
Steven R
SR
Food Science & Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville 32611-0370, USA.
Quinlivan
Eoin P
EP
Shelnutt
Karla P
KP
Ghandour
Haifa
H
Capdevila
Antonieta
A
Coats
Bonnie S
BS
Wagner
Conrad
C
Shane
Barry
B
Selhub
Jacob
J
Bailey
Lynn B
LB
Shuster
Jonathan J
JJ
Stacpoole
Peter W
PW
Gregory
Jesse F
JF
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
D000596:Amino Acids; D006710:Homocysteine; D012694:Serine; D005492:Folic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007930:Leucine