生物钟基因研究进展.pptVIP

Toxicology-chapter 3 * Definition Conversion of lipophilic xenobiotics to water-soluble chemicals by a process catalyzed by enzymes in the liver and other tissues. In most cases, biotransformation lessens the toxicity of xenobiotics, but many must undergo the process to exert their toxic effects. Toxicology-chapter 3 * General principles Broad specificity of xenobiotic biotransforming enzymes such as P450 enzymes. Biotrasformation versus metabolism Sterrochemical difference of biotransformation may lead to different metabolites Phase I and Phase II biotransformation Toxicology-chapter 3 * Phase I and phase II biotransformation Section 4 Toxicology-chapter 3 * Phase I biotransformation Hydrolysis: functional group such as carboxylic羧基,acid ester, amide, thioester, acid anhydride Reduction: azo- and nitro-, carbonyl, disulfide, sulfoxide, quinone, dihydropyrimidine Oxidation: alcohol, aldehyde, ketone, monoamine, aromatization, molybdenum, flavin Key oxidation enzyme: cytochrome P450 Toxicology-chapter 3 * Cytochrome P450 Activation of xenobiotics by P450 leads in most cases to detoxication, but some toxicities like tumorigenicity of a chemical depends on its activation. Some P450 enzymes in human liver microsomes are inducible which usually lowers blood level of the xenobiotics. Inhibition of P450 falls into 3 categories: the competition between 2 chemicals metabolized by the same P450; by different P450; and by suicide inactivation. Toxicology-chapter 3 * Cytochrome P450  Toxicology-chapter 3 * Phase II biotransformation Reactions: glucuronidation, sulfonation, acetylation, methylation Conjugation with glutathione and amino acid can result in a large increase in xenobiotic hydrophilicity to greatly promote the excretion of foreign chemicals Most phase II biotransforming enzymes are mainly located in the cytosol, and the reactions are much faster than phase I reactions 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 * 卫生毒理学 *