Multiplicity and physiological role of primatial dihydrodiol dehydrogenase involved in the detoxification of carcinogenic aromatic hydrocarbons

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(1) Four monomeric difiydrodiol dehydrogenases (DD) with Mr 35,000 - 39,000 were isolated from monkey liver. One major enzyme with a pI value of 8.7, although showed high indanol dehydrogenase activity, oxidized reversively 3alpha- or 20alpha- hydroxy group of bile acids and 5beta-pregnanes at low Km values, which suggests that the enzyme acts as a 3(20)alpha-hydroxysteroid dekiydrogenase in the metabolism of certain steroid hormones and bile acids. The enzyme's amino acid composition, stereospecificity of hydrogen transfer and kinetic mechanisms of the reaction and inhibition by specific inhibitors were determined. The other three DDs were identified as an isomer of the pI 8.7 enzyme, aldehyde reductase and 3alpha-hydroxy- steroid dehydrogenase.(2) Kidney exhibited the highest DD activity of monkey tissues, and a dimeric DD with Mr 78,000 was isolated from this tissue. The enzyme was chemically and immunologically distinct from the liver enzymes and occurred specifically in kidney, in which it was mainly localized in the proximal tubule. Dihydroxyacetone phosphate was reduced by the enzyme.(3) Human liver contained at least four multiple forms of DD, and three NADP- dependent DD with Mr 35,000 and one NAD-dependent DD with Mr 80,000 were purified. The major enzyme was identified as aldehyde reductase, and the catalytic properties of the other two NADP-dependent enzymes were similar to the pI 8.7 DD and 3alpha-hydroxysteroid dehydrogenase of monkey liver, whereas the properties of the NAD-dependent enzyme wire identical to those of alcohol dehydrogenase.(4) Only one enzyme species was detected in liuman kidriey. The isolated enzyme was identified as aldehyde reductase.