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.
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.
Lamers
Yvonne
Y
Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA.
Williamson
Jerry
J
Ralat
Maria
M
Quinlivan
Eoin P
EP
Gilbert
Lesa R
LR
Keeling
Christine
C
Stevens
Robert D
RD
Newgard
Christopher B
CB
Ueland
Per M
PM
Meyer
Klaus
K
Fredriksen
Ase
A
Stacpoole
Peter W
PW
Gregory
Jesse F
JF
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
D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D003540:Cystathionine; D012694:Serine; D025101:Vitamin B 6; D005998:Glycine