STUDIES ON THE ACTIVE SITES OF CYTOCHROMES P-450

细胞色素P-450酶是单加氧酶家族 负责氧化各种内源性和 外源化合物 广泛的底物特异性和多样性 这些同工酶的氧化机制使得难以 预测参与给定代谢的途径 化合物. 可以合理地解释， 给定酶-底物复合物的代谢是以下的函数： 两个因素：1）酶中底物的方向 同工酶的活性位点; 2）底物的倾向性 氧化官能团。 对两者的理解 每种同工酶的这些因素以及 存在的每种同工酶的量，对于预测 药物代谢 这些研究正在进行中，以探讨这两个 影响因素及其相互作用：1）细胞色素P-450 a的研究 活性位点。 2)理论和实验研究 官能团的氧化和3）理论和实验 芳香化酶氧化机理的研究。

The cytochrome P-450 enzymes are a family of monooxygenases responsible for the oxidation of a wide variety of endogenous and exogenous compounds. The broad substrate specificities and diverse mechanisms of oxidation of these isozymes makes it difficult to predict the pathways involved in the metabolism of a given compound. It can be rationalized that the regio-specificity of metabolism for a given enzyme-substrate complex is a function of two factors: 1) the orientation(s) of the substrate in the enzymes active site of the isozyme, and 2) the tendency of the substrates functional groups toward oxidation. An understanding of both of these factors for each isozyme together with knowledge of the amounts of each isozyme present, are necessary for predictions in drug metabolism. These studies are in progress to probe these two factors and their interaction: 1) studies of the cytochrome P-450a active sites. 2) theoretical and experimental studies on the oxidation of functional groups and 3) theoretical and experimental studies on the mechanism of aromatase oxidations.