title: 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 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-(13)C(2)]glycine and [5,5,5-(2)H(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 micromol x kg(-1) x h(-1) (P < 0.05), but serine production using a GCS-derived 1-carbon unit (93 +/- 9 vs. 91 +/- 6 micromol x kg(-1) x h(-1)) and glycine cleavage (163 +/- 11 vs. 151 +/- 8 micromol x kg(-1) x h(-1)) were not changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate (approximately 140-170 micromol x kg(-1) x h(-1)) that greatly exceeds the demand for remethylation and transmethylation processes (approximately 4-7 micromol x kg(-1) x 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.
authors.affiliation: Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lamers
authors.forename: Jerry
authors.initials: J
authors.lastname: Williamson
authors.forename: Maria
authors.initials: M
authors.lastname: Ralat
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Quinlivan
authors.forename: Lesa R
authors.initials: LR
authors.lastname: Gilbert
authors.forename: Christine
authors.initials: C
authors.lastname: Keeling
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Ase
authors.initials: A
authors.lastname: Fredriksen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
mesh_terms: D000328:Adult; D003540:Cystathionine / Q000097:blood*; D004032:Diet; D005260:Female; D005998:Glycine / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008297:Male; D012694:Serine / Q000097:blood / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D025101:Vitamin B 6 / Q000494:pharmacology*; D026681:Vitamin B 6 Deficiency / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D003540:Cystathionine; D012694:Serine; D025101:Vitamin B 6; D005998:Glycine