NADPH-dependent cytosolic reductase

NADPH-dependent cytosolic reductases are a broad class of enzymes, primarily comprising the aldo-keto reductase (AKR) and carbonyl reductase (CBR) superfamilies, that catalyze the reduction of carbonyl groups to alcohols using NADPH as a hydride donor (Penning, 2015). These enzymes are essential for the metabolism of endogenous substrates such as steroids, prostaglandins, and biogenic amines, as well as the detoxification of reactive aldehydes produced during lipid peroxidation (Rosemond & Walsh, 2004). In pharmacology, they are significant for their role in the Phase I metabolism of drugs, notably the conversion of anthracycline antibiotics like doxorubicin into their cardiotoxic alcohol metabolites, such as doxorubicinol (Forrest et al., 1991). Specific enzymes within this group, such as aldose reductase (AKR1B1), are therapeutic targets for treating diabetic complications like neuropathy and retinopathy by preventing the accumulation of sorbitol (Gabbay, 2004). Additionally, enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1) are targeted in oncology for the bioactivation of quinone-based prodrugs (Ross & Siegel, 2021). Because the term encompasses multiple distinct enzyme families with diverse substrates and physiological roles, it is generally considered a functional category rather than a single molecular target.

Other names

Carbonyl reductaseAldo-keto reductaseNADPH-dependent oxidoreductaseCytosolic carbonyl reductase

Inhibition of enzymatic reduction of carbonyl-containing substrates to prevent metabolic inactivation or toxic metabolite formation; bioactivation of quinone-containing prodrugs.