Vitamin B6 dependence of one-carbon metabolism quantified in human subjects

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The acquisition and transfer of one-carbon units is of major relevance in the synthesis of DNA, neurotransmitters, and membranes of the nervous system. The amino acids glycine, serine, and methionine are major participants in one-carbon metabolism either as donor or acceptor of onecarbon units. Vitamin B6 in form of pyridoxal-5’-phosphate is a coenzyme in multiple reactions of the one-carbon metabolism including the release of one-carbon units from glycine and serine. Marginal vitamin B6 deficiency is common world-wide and has been associated with increased risk of coronary artery disease, stroke, and Alzheimer’s Disease; however, its physiological consequences have been poorly characterized. With the use of stable isotope tracers, the research aims to quantify postprandial kinetics of glycine, serine, and methionine and the dependence of their kinetics on vitamin B6 status. Two infusion protocols using glycine tracers have been performed for determination of the rates of in vivo glycine turnover, glycine-based generation of one-carbon units, and the synthesis of the antioxidant glutathione in healthy men and women. A third human tracer infusion protocol will determine the effect of vitamin B6 deficiency on the kinetics of the methionine cycle, the regeneration/remethylation of methionine and the transsulfuration pathway. The results of all kinetic studies will aid in generating new knowledge of human one-carbon metabolism and in better understanding the impact of vitamin B6 status on related diseases.