CBR3

Carbonyl reductase 3 (CBR3) is a member of the short-chain dehydrogenase/reductase (SDR) superfamily and functions as a monomeric NADPH-dependent oxidoreductase that catalyzes the reduction of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols^[1][2]. Mechanistically, CBR3 participates in carbonyl detoxification and xenobiotic metabolism, processes that regulate the cellular handling of endogenous reactive carbonyls and therapeutic agents^[3][4]. The gene was mapped to chromosome 21q22.2 and is closely linked to CBR1, supporting its classification within the monomeric carbonyl reductase family while indicating a distinct genetic locus and regulatory context^[1]. In disease-relevant settings, CBR3 has attracted attention because genetic variation alters enzymatic activity toward pharmacologically important substrates, including anthracycline-related compounds, thereby influencing interindividual differences in drug metabolism^[2][5]. Compared with the closely related isoform CBR1, CBR3 exhibits distinct functional properties and substrate-recognition characteristics, indicating nonredundant biological roles despite substantial sequence similarity^[4][6]. Experimental studies further demonstrated that the common CBR3 V244M variant encodes enzymes with different catalytic efficiencies and NADP(H)-dependent kinetic properties, making this polymorphism a useful model for investigating carbonyl reduction pathways and pharmacogenomic mechanisms^[2]. Regulation of CBR3 expression by the oxidative stress-responsive transcription factor Nrf2 additionally links this enzyme to cellular redox adaptation and xenobiotic response networks^[3].

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