Glutamylases

Glutamylases are enzymes that act on substrates containing the amino acid glutamate, with particular emphasis on bonds involving the gamma-glutamyl linkage found in glutathione and related peptides. The best-known members of this group are gamma-glutamyl transferases (GGTs) and gamma-glutamyl hydrolases (GGHs). GGTs catalyze transfer of gamma-glutamyl groups from glutathione to acceptor molecules, whereas GGHs hydrolyze gamma-glutamyl bonds to release free glutamate or glutamyl-containing products. Collectively, these activities participate in the gamma-glutamyl cycle, a pathway that supports glutathione turnover, amino acid transport, and detoxification.

GGTs are typically membrane-associated enzymes present on the surfaces of cells in liver, kidney, pancreas, and other tissues in animals; related enzymes occur in soluble forms in plants and bacteria. GGTs enable the extracellular processing of glutathione and related peptides, contributing to intracellular glutathione homeostasis and nutrient transport. GGHs are soluble hydrolases that cleave gamma-glutamyl bonds to recycle glutamate and to generate downstream products such as cysteinylglycine.

Physiological roles of glutamylases include maintenance of cellular redox balance through glutathione metabolism, facilitation of amino acid uptake via gamma-glutamyl peptides, and involvement in detoxification pathways. Clinically, elevated levels of GGT activity in blood are a common biomarker for hepatobiliary disease and chronic alcohol use, while alterations in glutamylase activity can reflect metabolic or oxidative stress states. Because the term glutamylases is applied variably, it generally refers to enzymes acting on gamma-glutamyl substrates rather than to all enzymes that process glutamate. See also gamma-glutamyl transpeptidase, gamma-glutamyl hydrolase, and glutathione.