Biological characteristics and functions of glutathione cytoplasmic degrading enzyme ChaC1 / 中国生物化学与分子生物学报

ABSTRACT

Glutathione is a tri-peptide that plays key roles in antioxidation and detoxification. At present, research on glutathione metabolism mainly focuses on anabolism. And little is known about its catabolismin the cytoplasm. With the discovery of glutathione-specific γ-glutamylcyclotransferase ChaC1, thecatabolism of glutathione in the cytoplasm has gradually been unveiled. ChaC1 is one member of the γ-glutamylcyclotransferase (GGCT) family, catalyzing the degradation of glutathione and production of Cys-Gly and 5-oxoproline. ChaC1 is highly conserved, with a ~ 88% identity between human and mousegenes. Mutation of E115 in human ChaC1 or E116 in mouse ChaC1 abolishes its enzymatic activity. Notably, ChaC1 deficiency leads to embryonic lethality in the mouse and zebrafish, indicating ChaC1 isessential for embryo development. On the other side, ChaC1 is highly expressed in different types ofcancer and correlates with a poor prognosis, suggesting that ChaC1 also has important pathophysiologicalfunction. In this paper, we review the research progress on the structure, enzymatic activity andexpression pattern of ChaC1 in recent years, and summarize the role of ChaC1 in development anddiseases, providing new insights on the mechanisms and therapeutic strategies.