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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 281; no. 6; pp. E1182 - E1190
• Main Authors: Cuskelly, Geraldine J., Stacpoole, Peter W., Williamson, Jerry, Baumgartner, Thomas G., Gregory, Jesse F.
• Format: Journal Article
• Language: English
• Published: 01.12.2001
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.2001.281.6.E1182

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) μmol/l] was approximately two times that of control (7.4 ± 1.7 μmol/l) and vitamin B 6 -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 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.