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 Women1,2

• Published in: The Journal of nutrition Vol. 139; no. 3; p. 452
• Main Authors: Lamers, Yvonne, Williamson, Jerry, Ralat, Maria, Quinlivan, Eoin P, Gilbert, Lesa R, Keeling, Christine, Stevens, Robert D, Newgard, Christopher B, Ueland, Per M, Meyer, Klaus, Fredriksen, Ase, Stacpoole, Peter W, Gregory, Jesse F
• Format: Journal Article
• Language: English
• Published: Bethesda American Institute of Nutrition 01.03.2009
• Subjects: Alzheimer's disease; Chronic illnesses; Diet; Drug use; Low density lipoprotein; Mass spectrometry; Nutrition; Nutrition research; Physical examinations; Plasma; Ribonucleic acid; RNA; Vitamin B; Vitamin deficiency
• ISSN: 0022-3166; 1541-6100

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-^sup 13^C^sub 2^lglycine and [5,5,5-^sup 2^H^sub 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 ± 9 µmol.kg^sup -1^.h^sup -1^ (P < 0.05), but serine production using a GCS-derived 1-carbon unit (93 ± 9 vs. 91 ± 6 µmol.kg^sup -1^.h^sup -1^) and glycine cleavage (163 ± 11 vs. 151 ± 8 µmol.kg^sup -1^.h^sup -1^) were not changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate (~140-170 µmol.kg^sup -1^.h^sup -1^) that greatly exceeds the demand for remethylation and transmethylation processes (~4-7 µmol.kg^sup -1^.h^sup -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. [PUBLICATION ABSTRACT]