Division of Molecular Cell Biology, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata City 990-9585, Japan.
Cells. 2023 Dec 13;12(24):2831. doi: 10.3390/cells12242831.
L-γ-Glutamyl-L-cysteinyl-glycine is commonly referred to as glutathione (GSH); this ubiquitous thiol plays essential roles in animal life. Conjugation and electron donation to enzymes such as glutathione peroxidase (GPX) are prominent functions of GSH. Cellular glutathione balance is robustly maintained via regulated synthesis, which is catalyzed via the coordination of γ-glutamyl-cysteine synthetase (γ-GCS) and glutathione synthetase, as well as by reductive recycling by glutathione reductase. A prevailing short supply of L-cysteine (Cys) tends to limit glutathione synthesis, which leads to the production of various other γ-glutamyl peptides due to the unique enzymatic properties of γ-GCS. Extracellular degradation of glutathione by γ-glutamyltransferase (GGT) is a dominant source of Cys for some cells. GGT catalyzes the hydrolytic removal of the γ-glutamyl group of glutathione or transfers it to amino acids or to dipeptides outside cells. Such processes depend on an abundance of acceptor substrates. However, the physiological roles of extracellularly preserved γ-glutamyl peptides have long been unclear. The identification of γ-glutamyl peptides, such as glutathione, as allosteric modulators of calcium-sensing receptors (CaSRs) could provide insights into the significance of the preservation of γ-glutamyl peptides. It is conceivable that GGT could generate a new class of intercellular messaging molecules in response to extracellular microenvironments.
L-γ-谷氨酰-L-半胱氨酰-甘氨酸通常被称为谷胱甘肽（GSH）；这种无处不在的巯基在动物生命中起着至关重要的作用。GSH 的主要功能是与谷胱甘肽过氧化物酶（GPX）等酶发生共轭和电子供体反应。通过受调控的合成来强有力地维持细胞内谷胱甘肽平衡，该合成通过 γ-谷氨酰半胱氨酸合成酶（γ-GCS）和谷胱甘肽合成酶的协调以及谷胱甘肽还原酶的还原循环来催化。由于 γ-GCS 的独特酶特性，L-半胱氨酸（Cys）的普遍供应不足往往会限制谷胱甘肽的合成，从而导致产生各种其他 γ-谷氨酰肽。γ-谷氨酰转移酶（GGT）通过细胞外降解谷胱甘肽是一些细胞中 Cys 的主要来源。GGT 催化谷胱甘肽的 γ-谷氨酰基的水解去除，或将其转移到细胞外的氨基酸或二肽上。这些过程依赖于丰富的受体底物。然而，细胞外保存的 γ-谷氨酰肽的生理作用长期以来一直不清楚。鉴定谷胱甘肽等 γ-谷氨酰肽作为钙敏感受体（CaSRs）的别构调节剂，可以深入了解保存 γ-谷氨酰肽的重要性。可以想象，GGT 可以针对细胞外微环境生成一类新的细胞间通讯分子。
