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Dietary Glycine Alters One‐Carbon Metabolic kinetics in vivo
Author(s) -
Huang YuHsuan,
Chiang EnPei Isabel
Publication year - 2016
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.30.1_supplement.272.4
Subject(s) - glycine , biochemistry , sarcosine , methionine , serine , metabolism , chemistry , biosynthesis , glycine cleavage system , methionine synthase , endogeny , homocysteine , serine hydroxymethyltransferase , amino acid , enzyme
Folate‐dependent one‐carbon metabolism is required for nucleotide biosynthesis and for the remethylation of homocysteine to methionine. Glycine‐N methyltransferase (GNMT) is a major hepatic enzyme that converts S ‐adenosylmethionine to S ‐adenosylhomocysteine while generating sarcosine from glycine, hence it can regulate mediating methyl group availability in mammalian cells. The metabolic role of GNMT in folate‐mediated one‐carbon metabolism and how glycine supply may affect one carbon metabolic kinetics are not fully understood. In the present study, we investigated how GNMT expression may affect cellular one carbon flow under various glycine conditions. Hepatocyte‐derived cell‐lines with and without GNMT expression were cultured in minimum essential medium (MEM) with and without high glycine supply. Methylene‐tetrahydrofolate (mTHF) utilization and endogenous formate biosynthesis were carefully investigated using stable isotopic tracers and GC‐MS. We discovered that high glycine inhibits the M+1 specie enrichments in deoxythymidine (dT+1) from 2,3,3 D3‐serine, suggesting that high glycine may inhibit endogenous formate production in these in vitro models. In a parallel experiment that exogenous formate was used as the 1C source, enrichments in dT+1 significantly increased from exogenous formate, supporting our hypothesis that high glycine inhibits endogenous format production for thymidine synthesis. On the other hand, high glycine promotes M+1 specie enrichments in methionine from 2,3,3 D3‐serine, indicating that high glycine supply may favor the utilization of methyleneTHF derived one carbon for homocysteine remethylation. High glycine supply can promote folate dependent methionine synthesis in our cell models. Furthermore, our preliminary in vivo experiments demonstrated that high dietary glycine can promote folate dependent methionine synthesis, consistent with our in vitro findings. These results showed that high dietary glycine promotes methionine remethylation in vitro and in vivo . Support or Funding Information supported by MOST 104‐2320‐B005‐010‐MY3; MOST104‐2911‐I005‐301; and Ministry of Education, Taiwan, R.O.C. under the ATU plan