Enzyme-catalyzed detoxication reactions: mechanisms and stereochemistry.
Enzyme catalyzed detoxication reactions are one of the primary defenses organisms have against chemical insult. This article reviews current chemical approaches to understanding the cooperative role of enzymes in the metabolism of foreign compounds. Emphasis is placed on chemical and stereochemical studies which help elucidate the mechanism of action and active-site topologies of the detoxication enzymes. The stereoselectivity of the cytochromes P-450 and flavin containing monooxygenases as well as the role of hemoglobin and lipid peroxidation in the primary metabolism of xenobiotics is discussed. Current knowledge of the mechanism and stereoselectivity of epoxide hydrolase is also presented. Three enzymes involved in secondary metabolism of xenobiotics, UDP-glucuronosyltransferase, sulfotransferase and glutathione S-transferase are discussed with particular emphasis on active site topology and cooperative participation with the enzymes of primary metabolism.
D000818:Animals; D002384:Catalysis; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D008968:Molecular Conformation; D013379:Substrate Specificity; D013466:Sulfurtransferases / Q000378:metabolism
D004798:Enzymes; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D013466:Sulfurtransferases; D004851:Epoxide Hydrolases