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Vitamin B6 dependent glycine flux and decarboxylation rate quantified in human subjects after primed, constant infusions of [1,2‐13C2]glycine and [2H3]leucine
Author(s) -
Lamers Yvonne,
Williamson Jerry,
Gilbert Lesa R.,
Stacpoole Peter W.,
Gregory Jesse F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a345-d
Subject(s) - serine hydroxymethyltransferase , glycine cleavage system , glycine , decarboxylation , chemistry , serine , methionine , leucine , flux (metallurgy) , vitamin , biochemistry , amino acid , enzyme , organic chemistry , catalysis
Glycine is a precursor in the synthesis of DNA, protein, glutathione, and one‐carbon units. Glycine decarboxylation through glycine cleavage system ( GCS ) and glycine‐serine transformation by serine hydroxymethyltransferase ( SHMT ) require pyridoxal phosphate (PLP) as coenzyme. Primed, constant infusions of 9.26 μmol/(kg*h) [1,2‐ 13 C 2 ]glycine and 1.87 μmol/(kg*h) [5,5,5‐ 2 H 3 ]leucine were used to quantify whole body glycine flux, flux of glycine decarboxylation, glycine to serine flux, and their dependence on vitamin B6 status in healthy volunteers (4 male, 1 female; aged 21–34y). Mean (± SEM) concentration of plasma PLP decreased from 59 ± 20 nmol/L to 23 ± 4 nmol/L during a 28‐d vitamin B6‐restricted diet. The rate of [ 13 C 2 ]serine synthesis derived from [ 13 C 2 ]glycine via SHMT was 183 ± 5 μmol/(kg*h) pre and 202 ± 18 μmol/(kg*h) post vitamin B6 restriction. The rate of [ 13 C 1 ]serine synthesis via GCS and SHMT was 80 ± 12 μmol/(kg*h) before and 78 ± 12 μmol/(kg*h) after the diet. No significant enrichment of methionine was detected at the glycine infusion rate used. Breath CO 2 data show a glycine decarboxylation rate of 66.6 ± 8.3 μmol/(kg*h) and 59.7 ± 4.0 μmol/(kg*h), respectively, indicating that GCS accounted for 37 ± 4% and 32 ± 2% of whole body glycine flux, respectively, before and after vitamin B6 restriction. Supported by NIH grant DK072398 and GCRC grant M01‐RR00082.