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Tracing of glycine carbons in healthy men and women using primed, constant infusion of [1‐ 13 C 1 ]glycine or [1,2‐ 13 C 2 ]glycine and [ 2 H 3 ]leucine
Author(s) -
Lamers Yvonne,
Williamson Jerry,
Gilbert Lesa R.,
Keeling Christine,
Stacpoole Peter W.,
Gregory Jesse F.
Publication year - 2008
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.22.1_supplement.869.31
Subject(s) - glycine , glycine cleavage system , serine hydroxymethyltransferase , decarboxylation , chemistry , serine , amino acid , stereochemistry , enzyme , biochemistry , catalysis
Glycine undergoes decarboxylation in the glycine cleavage system ( GCS ) to yield CO 2 , NH 3 , and a one‐carbon unit. CO 2 also can be generated from the 2‐carbon of glycine by 10‐formyltetrahydrofolate‐dehydrogenase and, after glycine‐to‐serine conversion by serine hydroxymethyltransferase ( SHMT ), from the TCA cycle. To evaluate the relative fates of glycine carbons in CO 2 generation in healthy volunteers (3 male, 3 female; aged 21–26y), primed, constant infusions were conducted using 9.26 μmol/(kg*h) of [1,2‐ 13 C 2 ]glycine and 1.87 μmol/(kg*h) of [5,5,5‐ 2 H 3 ]leucine, followed by an infusion protocol using [1–13C1]glycine as the glycine tracer. The rate of serine synthesis via SHMT was 186 ± 10 μmol/(kg*h) (mean ± SEM) after infusion of [1‐ 13 C 1 ]glycine and 185 ± 18 μmol/(kg*h) after infusion of [1,2‐ 13 C 2 ]glycine. Using the [1‐ 13 C 1 ]glycine tracer, breath CO 2 data showed a glycine decarboxylation rate of 96 ± 3 μmol/(kg*h), which indicated that GCS accounted for 22 ± 1% of whole body glycine flux. Infusion of [1,2‐ 13 C 2 ]glycine yielded a glycine‐to‐CO 2 flux of 146 ± 15 μmol/(kg*h). By difference, this implies a rate of CO 2 formation from the glycine 2‐carbon of 51 ± 16 μmol/(kg*h), which accounts for ~35% of the CO 2 generated in glycine catabolism. The results from the [1‐ 13 C 1 ]glycine tracer indicate an equally high rate (~96 μmol/(kg*h)) of production of one‐carbon units by the GCS. Supported by NIH grant DK072398 and GCRC grant M01‐RR00082