Gamma-glutamyltransferase 1 (GGT1)

Gamma-glutamyltransferase 1 (GGT1) is a membrane-associated heterodimeric enzyme (heavy and light chains derived from a single precursor) that catalyzes transfer or hydrolysis of γ-glutamyl bonds, primarily from glutathione, generating glutamate and enabling amino acid acceptor conjugates; it is central to the gamma-glutamyl cycle, drug/xenobiotic detoxification, and redox regulation. The active site resides in the light subunit and features an N-terminal nucleophile threonine forming a γ-glutamyl–enzyme intermediate; key conserved residues engaged in γ-glutamyl recognition have been defined structurally. Clinically, GGT activity is a widely used biomarker (notably in liver and biliary disease), and GGT1 is also known as CD224, with multiple transcript variants and expression in tissues involved in absorption and secretion.

Other names

CD224Gamma-glutamyl transpeptidase 1γ-Glutamyltransferase 1GGTP1EC 2.3.2.2 (enzyme classification applies to GGT enzymes, including GGT1)

Irreversible inhibition of the catalytic N-terminal nucleophile threonine in the light chain by electrophilic inhibitors (e.g., acivicin) blocking γ-glutamyl transfer/hydrolysis; Competitive/substrate-like engagement of the γ-glutamyl binding pocket governing transfer to amino acids/peptides or hydrolysis by water