Batt A M, Magdalou J, Vincent-Viry M, Ouzzine M, Fournel-Gigleux S, Galteau M M, Siest G
Centre du Médicament, URA CNRS 597, Nancy, France.
Clin Chim Acta. 1994 May;226(2):171-90. doi: 10.1016/0009-8981(94)90214-3.
Many studies on drug metabolism have been carried out during the last decades using protein purification, molecular cloning techniques and analysis of polymorphisms at phenotype and genotype levels. These researchers led to a better understanding of the role of drug metabolizing enzymes in the biotransformation of drugs, pollutants or foreign compounds and of their use in laboratory medicine. The metabolic processes commonly involved in the biotransformation of xenobiotics have been classified into functionalization reaction (phase I reactions), which implicate lipophilic compounds. These molecules are modified via monooxygenation, dealkylation, reduction, aromatization, hydrolysis and can be substrates for the phase II reactions, often called conjugation reactions as they conjugate a functional group with a polar, endogenous compound. This review, devoted to cytochromes P-450 (CYP) and UDP-glucuronosyltransferases (UGT), describes essentially the genetic polymorphisms found in humans, their clinical consequences and the methods to assess the phenotypes or genotypes, with a view to studying the interindividual differences in drug monooxygenation and drug glucuronidation. Variations in drug glucuronidation reported here focused essentially on variations due to physiological factors, induction, drug interactions and genetic factors in disorders such as Gilbert's Syndrome and Crigler-Najjar type I and II diseases.
在过去几十年里，人们利用蛋白质纯化、分子克隆技术以及表型和基因型水平的多态性分析，开展了许多关于药物代谢的研究。这些研究使人们对药物代谢酶在药物、污染物或外来化合物生物转化中的作用以及它们在实验医学中的应用有了更深入的了解。外源性物质生物转化中常见的代谢过程已被分类为官能化反应（I相反应），该反应涉及亲脂性化合物。这些分子通过单加氧作用、脱烷基作用、还原作用、芳构化作用、水解作用进行修饰，并且可以作为II相反应的底物，II相反应通常称为结合反应，因为它们将一个官能团与一种极性内源性化合物结合。这篇综述聚焦于细胞色素P-450（CYP）和尿苷二磷酸葡萄糖醛酸基转移酶（UGT），主要描述了在人类中发现的基因多态性、它们的临床后果以及评估表型或基因型的方法，旨在研究药物单加氧作用和药物葡萄糖醛酸化的个体间差异。这里报道的药物葡萄糖醛酸化的变化主要集中在生理因素、诱导作用、药物相互作用以及诸如吉尔伯特综合征和I型及II型克里格勒 - 纳贾尔病等疾病中的遗传因素所导致的变化。
