Deficiencies of folate and vitamin B6exert distinct effects on homocysteine, serine, and methionine kinetics

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Abstract
Folate and vitamin B6act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B6deficiency 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 B6deficiency. 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 B6and folate deficiencies.