Carbonyl reductase [NADPH] 1

Definition:

NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione. In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue.

References:

[1]. Raynard L Bateman, et al. Human carbonyl reductase 1 is an S-nitrosoglutathione reductase. J Biol Chem. 2008 Dec 19;283(51):35756-62. [Content Brief]

[2]. Masahiro Tanaka, et al. An unbiased cell morphology-based screen for new, biologically active small molecules. PLoS Biol. 2005 May;3(5):e128. [Content Brief]

[3]. Raynard Bateman, et al. Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct. Org Biomol Chem. 2007 Oct 21;5(20):3363-7. [Content Brief]

[4]. G L Forrest, et al. Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. Mol Pharmacol. 1991 Oct;40(4):502-7. [Content Brief]

[5]. Ruth A Morgan, et al. Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity. Sci Rep. 2017 Sep 6;7(1):10633. [Content Brief]

[6]. Vanessa Gonzalez-Covarrubias, et al. Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER). Pharm Res. 2008 Jul;25(7):1730-4. [Content Brief]

[7]. Vanessa Gonzalez-Covarrubias, et al. A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity. Drug Metab Dispos. 2007 Jun;35(6):973-80. [Content Brief]

[8]. B Wermuth, et al. Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. J Biol Chem. 1981 Feb 10;256(3):1206-13. [Content Brief]

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