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

Folate and vitamin B-6 act in generating methyl groups for homocysteine rem ethylation, but the kinetic effects of folate or vitamin B-6 deficiency are not known. We used an intravenous primed, constant infusion of stable isot ope-labeled serine, methionine, and leucine to investigate one-carbon metab olism 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 tw o 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 r emethylation was depressed (P = 0.027) in folate deficiency but not in vita min B-6 deficiency. For all subjects, the homocysteine remethylation rate w as not significantly associated with plasma homocysteine concentration (r = -0.44, P = 0.12). The fractional synthesis rate of homocysteine from methi onine was positively correlated with plasma homocysteine concentration (r = 0.60, P = 0.031), and a model incorporating both homocysteine remethylatio n and synthesis rates closely predicted plasma homocysteine levels (r = 0.8 5, P = 0.0015). Rates of homocysteine remethylation and serine synthesis we re inversely correlated (r = -0.89, P < 0.001). These studies demonstrate d istinctly different metabolic consequences of vitamin B-6 and folate defici encies.