Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women

Abstract

Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as 5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine cleavage system (GCS) and glycine-serine transformation by serine hydroxymethyl-transferase (SHmT) require pyridoxal 5′-phosphate (PLP; active form of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in humans. Therefore, we determined the effects of vitamin B-6 restriction on whole-body glycine flux, the rate of glycine decarboxylation, glycine-to-serine conversion, use of glycine carbons in nucleoside synthesis, and other aspects of 1-carbon metabolism. We used a primed, constant infusion of [1,2- 13C 2]glycine and [5,5,5- 2H 3]leucine to quantify in vivo kinetics in healthy adults (7 males, 6 females; 20-39 y) of normal vitamin B-6 status or marginal vitamin B-6 deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55 ± 4 nmol/L (mean ± SEM) to 23 ± 1 nmol/L (P < 0.0001), which is consistent with marginal deficiency, whereas the plasma glycine concentration increased (P < 0.01).SHMT-mediated conversion of glycine to serine increased from 182 ± 7 to 205 ± 9μmol·kg -1·h -1 (P< 0.05), but serine production using a GCS-derived 1-carbon unit (93 ± 9 vs. 91 ± 6 μmol· kg -1·h -1) and glycine cleavage (163 ± 11 vs. 151 ± 8 μmol·kg -1·h -1) were not changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate (∼ 140-170 μmol·kg -1·h -1) that greatly exceeds the demand for remethylation and transmethylation processes (∼4-7 μmol·kg -1·h -1). We conclude that the in vivo GCS and SHMT reactions are quite resilient to the effects of marginal vitamin B-6 deficiency, presumably through a compensatory effect of increasing substrate concentration. © 2009 American Society for Nutrition.