RRC ID 58805
著者 Kobayashi S, Ikeda Y, Shigeno Y, Konno H, Fujii J.
タイトル γ-Glutamylcysteine synthetase and γ-glutamyl transferase as differential enzymatic sources of γ-glutamylpeptides in mice.
ジャーナル Amino Acids
Abstract Some γ-glutamylpeptides in blood plasma are putative biomarkers for pathological conditions of the liver. γ-Glutamyltransferase (GGT) and γ-glutamylcysteine synthetase (γ-GCS) are two such potential enzymes that are responsible for the production of γ-glutamylpeptides. GGT produces γ-glutamylpeptides by transferring the γ-glutamyl moiety from glutathione to an amino acid or a peptide. γ-GCS normally catalyzes the production of γ-glutamylcysteine from glutamate and cysteine in the glutathione-synthesizing reaction, but other amino acids can also serve as an acceptor of a γ-glutamyl group, thus resulting in the formation of a variety of γ-glutamylpeptides. Based on liquid chromatography-mass spectrometry analyses, we observed differences in the distribution of γ-glutamylpeptides between the liver and kidney and were able to measure the activities of γ-GCS as well as the GGT reactions by quantifying the resulting γ-glutamylpeptides. The enzymatic characterization of γ-GCS in liver homogenates indicated that several γ-glutamylpeptides including γ-glutamyltaurine are actually produced. Cys showed the lowest Km value (0.06 mM) while other amino acids had much higher Km values (ranging from 21 to 1800 mM). The moderate Km values for these amino acids suggest that they were not the preferred amino acids in this conversion but were utilized as acceptor substrates for the production of the corresponding γ-glutamylpeptides by the γ-GCS reaction under Cys-deficient conditions. Thus, the production of these γ-glutamylpeptides by γ-GCS is directly correlated with a low Cys content, suggesting that their measurement in blood plasma could be useful for predicting the presymptomatic disease state of the liver with a defect in GSH redox balance.
巻・号 52(4)
ページ 555-566
公開日 2020-4-1
DOI 10.1007/s00726-020-02835-2
PII 10.1007/s00726-020-02835-2
PMID 32170467
MeSH Amino Acids Animals Chromatography, Liquid Cysteine / metabolism Dipeptides / blood Dipeptides / metabolism* Glutamate-Cysteine Ligase / genetics Glutamate-Cysteine Ligase / metabolism* Glutathione / metabolism* Kidney / metabolism Liver / metabolism Mass Spectrometry Mice Peptides / chemistry Peptides / metabolism* gamma-Glutamyltransferase / metabolism*
IF 3.063
引用数 0
リソース情報
ヒト・動物細胞 Hepa 1-6(RCB1638)