Deficiencies of folate and vitamin B-6 exert distinct effects on homocysteine, serine, and methionine kinetics

G J Cuskelly, P W Stacpoole, J Williamson, T G Baumgartner, J F Gregory

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Abstract

Folate and vitamin B-6 act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B-6 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 B-6-deficient (n = 5) human subjects. The plasma homocysteine concentration in folate-deficient subjects [15.9 +/-2.1 (SD) mu mol/l] was approximately two times that of control (7.4 +/-1.7 mmol/l) and vitamin B-6-deficient (7.7 +/-2.1 mmol/l) subjects. The rate of methionine synthesis by homocysteine remethylation was depressed (P = 0.027) in folate deficiency but not in vitamin B-6 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 B-6 and folate deficiencies.

Original languageEnglish
Pages (from-to)E1182-E1190
Number of pages9
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume281
Issue number6
Publication statusPublished - Dec 2001

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