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

(1)从猴肝中分离到四个二氢二醇脱氢酶(DD)，其相对分子质量为35,000-39,000。一种主要的酶，其等电点为8.7，虽然表现出很高的吲哚脱氢酶活性，但在低Km值时，可反向氧化3α或20α-羟基胆汁酸和5β-孕烷，这表明该酶在某些类固醇激素和胆汁酸的代谢中起着3(20)α-羟基类固醇脱氢酶的作用。测定了该酶的氨基酸组成、氢转移的立体专一性以及反应的动力学机理和特定抑制剂的抑制作用。另外三个二聚体分别为等电点8.7酶、乙醛还原酶和3α-羟基类固醇脱氢酶的异构体。(2)肾脏的二聚体脱氢酶活性最高，并从该组织中分离到一个二聚体脱氢酶，其分子量为78,000。该酶在化学和免疫学上与肝酶不同，在肾脏中特异表达，主要定位于近端小管。(3)人肝中至少含有四种形式的DD，其中三种依赖NADP的DD的MR为35,000，一种依赖NAD的DD的MR为80,000。主要酶为乙醛还原酶，另外两种依赖NADP的酶的催化性质与猴肝的PI 8.7DD和3α-羟基类固醇脱氢酶相似，而依赖NAD的酶的性质与乙醇脱氢酶相同。(4)六满肾中只检测到一种酶。经鉴定，该酶为乙醛还原酶。

(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.