资源描述：
《化学结构和药物代谢chemicalstructureandmetabolism》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。
1、Chapter3Chemical StructureandMetabolism第三章 化学结构与药物代谢Section1IntroductionThephysicochemicalpropertiesofdrugsthatpredispose(使偏向于)themtogoodabsorption,suchaslipophilicity(亲脂性),areimpediment(妨碍)totheirelimination.Asaconsequence,theeliminationofdrugsnormallyrequi
2、restheirconversionintowatersolublecompoundsbyaprocessofmetabolism,whichenablesexcretionviaurineorfaeces(排泄物).MetabolismMetabolismisoftenthemajorfactordefiningthepharmacokineticsofdrugs,whichinturncaninfluencetheefficacyandside-effectprofileofthesecompounds.Th
3、echemicalnatureandmeansofidentificationofthesebiotransformationshavebeenwellknownformanyyears,butinrecentyearsmajoradvanceshavebeenmadeintheunderstandingoftheenzymesresponsibleforthemetabolicpathways.Section2EnzymesforDrugMetabolism（第二节药物代谢的酶）Thedrugmetaboliz
4、ingenzymesareusuallyclassifiedbythereactionstheycatalyse,aseitherPhaseIorPhaseII.PhaseIBiotransformationPhaseIreactionsintroduce,orotherwiseproduce,afunctionalgroup(e.g.–OH,-SH,-NH2,-COOH)intothemolecule.Thesereactionincludehydrolysis(水解),reduction(还原)andoxid
5、ation(氧化)andareperformedbyawiderangeofenzymes.OftenthesePhaseIreactionsprecedePhaseIIbiotransformations.第I相生物转化主要是官能团反应，包括对药物分子的氧化、还原和羟化等，在药物分子中引入或暴露极性基团，如羟基、羧基、巯基和氨基。PhaseIIBiotransformationPhaseIIreactionsinvolvetheconjugation(轭合)onasuitablechemicalgroupoft
6、hemolecule(parentcompoundormetabolite)andmanydrugscontainsuitablefunctionalgroupswithoutrecourse(依赖)toPhaseImetabolism.PhaseIIreactionsincludeconjugationwithglucuronic(葡萄糖醛酸)acid,sulfate,glutathione(谷光苷肽)oraminoacids(e.g.glycine(甘氨酸),taurine(牛磺酸),glutamine(谷氨
7、酰胺),allofwhichincreasethewatersolubilityofthemolecule.Conjugationreactions,suchasN-acetylationofaminesandN-,O-andS-methylation,generallyresultinmorelipophilicproducts.1.CytochromeP-450enzymesystem（CYP-450）(细胞色素P-450酶系)CytochromeP-450enzymesystem(CYP-450)areag
8、roupofnonspecificenzymes(Heme-coupledmonooxygenases)inlivermicrosomes.Inaanotherword,CYP450isaliverhomogenate(匀浆)fractionderivedfromsmoothendoplasmicreticulum(光滑内质网).CYP-450是一组铁原卟啉偶联单加氧酶，
