Microsomal reductase for aromatic aldehydes and ketones in guinea pig liver. Purification, characterization, and functional relationship to hexose-6-phosphate dehydrogenase.
An NADPH-specific aromatic aldehyde-ketone reductase located in guinea pig liver microsomes can be effectively solubilized with nonionic detergents, but not with bile salts and hydrolytic enzymes. Destruction of microsomal membranes by nonionic detergents or acetone treatment leads to significant activation of the reductase, indicating that the enzyme is partly latent in intact microsomes. After solubilization with Triton X-100, the reductase has been highly purified. The purified enzyme catalyzes the NADPH-linked reduction of xenobiotic aromatic aldehydes and ketones as well as 3-ketosteroids, notably 5 alpha- and 5 beta-dihydrotestosterones. The reductase activities for xenobiotic carbonyl compounds and for 3-ketosteroids are each inhibited by addition of the other type of substrate and show the same pH optimum, cofactor requirement, and heat stability, indicating the same enzyme is responsible for the reduction of the two types of substrates. Hexose-6-phosphate dehydrogenase, purified from guinea pig liver microsomes, acts as a more effective NADPH generator for the reductase than yeast and guinea pig liver cytosolic glucose-6-phosphate dehydrogenase. Evidence has been obtained that hexose-6-phosphate dehydrogenase undergoes a functional interaction with the reductase, facilitating the provision of NADPH to the reductase activity both in the reconstituted system and in microsomes.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D002850:Chromatography, Gel; D006168:Guinea Pigs; D007659:Ketones / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D008970:Molecular Weight; D009249:NADP / Q000378:metabolism; D017830:Octoxynol; D011092:Polyethylene Glycols; D012995:Solubility; D013379:Substrate Specificity
D000447:Aldehydes; D007659:Ketones; D011092:Polyethylene Glycols; D009249:NADP; D017830:Octoxynol; D000429:Alcohol Oxidoreductases; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase