Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase.
A nonspecific NADPH-dependent carbonyl reductase from human brain (formerly designated as aldehyde reductase 1; Ris, M. M., and von Wartburg, J. P. (1973) Eur. J. Biochem. 37, 69-77) has been purified to homogeneity. The enzyme reduces a number of biologically and pharmacologically active carbonyl compounds. Quinones, e.g. menadione, ubiquinone, and tocopherolquinone are the best substrates, followed by aldehydes containing an activated carbonyl moiety, e.g. 4-nitrobenzaldehyde or methylglyoxal. The enzyme also reduces ketones, e.g. prostaglandins of the E and A class, the anthracycline antibiotic daunorubicin and 3-ketosteroids. During catalysis the pro 4S hydrogen atom of the nicotinamide ring of NADPH is transferred to the substrate. Flavonoids, e.g. quercetin and rutin, indomethacin, ethacrynic acid, and dicoumarol inhibit the enzyme activity. 4-Hydroxymercuribenzoate and iodoacetate inactivate the enzyme. NADPH and substrate do not protect against the loss of activity. Carbonyl reductase consists of a single polypeptide chain with a molecular weight of 30,000. The native enzyme occurs in three molecular forms with similar substrate specificity and inhibitor sensitivity. The isoelectric points of the three enzyme species are 6.95, 7.85, and 8.5. In the presence of coenzyme the isoelectric points are shifted to 5.2 to 5.9. The comparison of structural and enzymic features of carbonyl reductase with other monomeric oxidoreductases suggests a close relationship of carbonyl reductase with prostaglandin 9-keto-reductase and xenobiotic ketone reductase.
D000429:Alcohol Oxidoreductases / Q000302:isolation & purification*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000596:Amino Acids / Q000032:analysis; D001921:Brain / Q000201:enzymology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D013379:Substrate Specificity
D000596:Amino Acids; D007527:Isoenzymes; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D006911:Hydroxyprostaglandin Dehydrogenases; D000449:Aldehyde Reductase; D007658:Ketone Oxidoreductases