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Am J Physiol Endocrinol Metab 281: E1182-E1190, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 6, E1182-E1190, December 2001

Deficiencies of folate and vitamin B6 exert distinct effects on homocysteine, serine, and methionine kinetics

Geraldine J. Cuskelly1, Peter W. Stacpoole2, Jerry Williamson1, Thomas G. Baumgartner3, and Jesse F. Gregory III1

1 Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences; 2 Division of Endocrinology and Metabolism, Department of Medicine, and Department of Biochemistry and Molecular Biology, College of Medicine; 3 Food and Nutrition Department, Shands Hospital at the University of Florida, and Division of Gastroenterology, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida 32611-0307

Folate and vitamin B6 act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B6 deficiency are not known. We used an intravenous primed, constant infusion of stable isotope-labeled serine, methionine, and leucine to investigate one-carbon metabolism in healthy control (n = 5), folate-deficient (n = 4), and vitamin B6-deficient (n = 5) human subjects. The plasma homocysteine concentration in folate-deficient subjects [15.9 ± 2.1 (SD) µmol/l] was approximately two times that of control (7.4 ± 1.7 µmol/l) and vitamin B6-deficient (7.7 ± 2.1 µmol/l) subjects. The rate of methionine synthesis by homocysteine remethylation was depressed (P = 0.027) in folate deficiency but not in vitamin B6 deficiency. For all subjects, the homocysteine remethylation rate was not significantly associated with plasma homocysteine concentration (r = -0.44, P = 0.12). The fractional synthesis rate of homocysteine from methionine was positively correlated with plasma homocysteine concentration (r = 0.60, P = 0.031), and a model incorporating both homocysteine remethylation and synthesis rates closely predicted plasma homocysteine levels (r = 0.85, P = 0.0015). Rates of homocysteine remethylation and serine synthesis were inversely correlated (r = -0.89, P < 0.001). These studies demonstrate distinctly different metabolic consequences of vitamin B6 and folate deficiencies.

one-carbon metabolism; remethylation; stable isotopes; human; vitamin B6; folate


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