Xu R, Cuebas D A
Department of Chemistry, Southwest Missouri State University, Springfield, 65804, USA.
Biochem Biophys Res Commun. 1996 Apr 16;221(2):271-8. doi: 10.1006/bbrc.1996.0585.
The ability of the bifunctional 2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase from rat liver peroxisomes to metabolize (24E)-3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA, a presumed intermediate during the beta-oxidative degradation of the steroid side chain in the formation of cholic acid, was investigated. The bifunctional enzyme efficiently hydrated the above compound specifically to (24S,25S)-3alpha, 7alpha, 12alpha, 24-tetrahydroxy-5beta-cholestanoyl-CoA, but the dehydrogenase component of the enzyme was virtually inactive toward this product. In contrast, the bifunctional enzyme efficiently catalyzed the dehydrogenation of the (24S,25R) diastereomer of the above hydroxy intermediate to two products whose uv absorbance and chemical properties were consistent with those of alpha-methyl-beta-ketoacyl-CoAs. These results suggest that the bifunctional enzyme is not sufficient for the formation of a 24-keto intermediate in bile acid biosynthesis.
对大鼠肝脏过氧化物酶体中的双功能2-烯酰辅酶A水合酶/3-羟基酰基辅酶A脱氢酶代谢（24E）-3α，7α，12α-三羟基-5β-胆甾-24-烯酰辅酶A（一种在胆酸形成过程中甾体侧链β氧化降解的假定中间体）的能力进行了研究。该双功能酶能有效地将上述化合物特异性水合为（24S，25S）-3α，7α，12α，24-四羟基-5β-胆甾烷酰辅酶A，但该酶的脱氢酶组分对该产物几乎无活性。相反，该双功能酶能有效地催化上述羟基中间体的（24S，25R）非对映异构体脱氢生成两种产物，其紫外吸收和化学性质与α-甲基-β-酮酰基辅酶A一致。这些结果表明，双功能酶不足以在胆汁酸生物合成中形成24-酮中间体。
