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3 Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, 4 General Clinical Research Center, 5 Division of Endocrinology and Metabolism, Department of Medicine, and 6 Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611; 7 Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704; and 8 Section for Pharmacology, Institute of Medicine, University of Bergen, and 9 Bevital A/S, Armauer Hansens Hus, 5021 Bergen, Norway
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 hydroxymethyltransferase (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 [1,2-13C2]glycine and [5,5,5-2H3]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–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.
* To whom correspondence should be addressed. E-mail: jfgy{at}ufl.edu.
Manuscript received 2 September 2008. Initial review completed 13 October 2008. Revision accepted 10 December 2008.
Published online 21 January 2009.
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Y. Lamers, B. O'Rourke, L. R Gilbert, C. Keeling, D. E Matthews, P. W Stacpoole, and J. F Gregory III Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women Am. J. Clinical Nutrition, August 1, 2009; 90(2): 336 - 343. [Abstract] [Full Text] [PDF] |
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