Carbonyl Reductase 1: A Redox-Regulating Carbonyl Detoxification Enzyme in Health and Disease

Carbonyl reductase 1 (CBR1) is a cytosolic monomeric enzyme belonging to the short-chain dehydrogenase/reductase superfamily and is ubiquitously expressed in human tissues. It catalyzes the NADPH-dependent reduction of a wide range of carbonyl compounds and plays a major role not only in phase I metabolism of xenobiotics, including drugs, but also in the metabolism of endogenous substrates such as prostaglandin E2, S-nitrosoglutathione, ketosteroids, and lipid peroxidation-derived aldehydes. Notably, glutathione binds near the active site of CBR1 and enhances its reductase activity toward non-glutathionylated substrates. Accumulating evidence indicates that CBR1 is involved in cancer, functioning either as a tumor suppressor or a tumor promoter depending on the cancer type. This dual role suggests that CBR1 functions as a context-dependent regulator of cellular redox adaptation. CBR1 is also implicated in several noncancerous diseases, including neurodegenerative disorders, diabetes, ischemia/reperfusion injury, osteoporosis, ulcerative colitis, and COPD. In this review, we summarize current knowledge on the structure, enzymatic functions, gene regulation, modulators, and polymorphisms of CBR1, and discuss its diverse roles in cancers and noncancerous disorders.