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.

中文翻译：

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γ-谷氨酰半胱氨酸合成酶和γ-谷氨酰转移酶是小鼠中γ-谷氨酰肽的差异酶源。

血浆中的某些γ-谷氨酰胺肽是肝脏病理状况的假定生物标记。γ-谷氨酰胺基转移酶（GGT）和γ-谷氨酰半胱氨酸合成酶（γ-GCS）是负责产生γ-谷氨酰肽的两种潜在酶。GGT通过将γ-谷氨酰基部分从谷胱甘肽转移到氨基酸或肽上而产生γ-谷氨酰基肽。γ-GCS通常在谷胱甘肽合成反应中催化由谷氨酸和半胱氨酸生产γ-谷氨酰半胱氨酸，但其他氨基酸也可以作为γ-谷氨酰基的受体，从而导致形成多种γ-谷氨酰胺。谷氨酰肽。基于液相色谱-质谱分析，我们观察到肝脏和肾脏之间γ-谷氨酰肽分布的差异，并且能够通过量化所得的γ-谷氨酰肽来测量γ-GCS的活性以及GGT反应。肝匀浆中γ-GCS的酶学表征表明，实际上产生了包括γ-谷氨酰基牛磺酸在内的几种γ-谷氨酰胺肽。Cys的Km值最低（0.06 mM），而其他氨基酸的Km值则高得多（21至1800 mM）。这些氨基酸的中等Km值表明，它们不是该转化中的首选氨基酸，而是用作在Cys缺乏条件下通过γ-GCS反应生成相应的γ-谷氨酰肽的受体底物。从而，