Dihydrodiol dehydrogenases in guinea pig liver

Abstract

Four major and four minor dihydrodiol dehydrogenases, with similar apparent molecular weights of 28,000 to 34,000 but with different charges, were purified from male guinea pig liver cytosol. One of the minor enzymes catalyzed only the oxidation of benzene dihydrodiol with a high K m value of 5.0 mM and was identified immunologically with aldehyde reductase. The other enzymes oxidized xenobiotic alicyclic alcohols and 17β-hydroxysteroids as well as benzene dihydrodiol. These enzymes exhibited higher affinity for 17β-hydroxysteroids than for alicyclic alcohols and benzene dihydrodiol, and immunologically cross-reacted with testosterone 17β-dehydrogenase purified from the same source. Four major enzymes and one minor with K m values for benzene dihydrodiol of about 0.2 mM, possessed specificity for 5β-androstane—17β-hydroxysteroids and dual cofactor requirement, whereas the other two minor enzymes with high K m values of over 5 mM showed apparent NADP and 5α-androstane specificity. The dihydrodiol dehydrogenase activity was localized in the cytosol of liver. The results indicate that the hepatic oxidation of dihydrodiols in the guinea pig is mediated by cytosolic testosterone 17β-dehydrogenase isozymes and aldehyde reductase. Testosterone 17β-dehydrogenase immunologically identical to the liver enzymes was detected only in kidney, whereas aldehyde reductase was detected in all tissues of the guinea pig.