药学专业英语视听教程 课件 lecture 3、4 Biochemistry、Pharmacology

中国药科大学ChinaPharmaceuticalUniversityLectureThreeBiochemistry中国药科大学ChinaPharmaceuticalUniversity中国药科大学ChinaPharmaceuticalUniversity中国药科大学ChinaPharmaceuticalUniversityholoenzymelocuscatalystkinasedeoxyribose中国药科大学ChinaPharmaceuticalUniversityplaque

geneticsbiologictriglycerideautophosphorylation中国药科大学ChinaPharmaceuticalUniversityacaseofemergentproperties3Dstructure-basedfunction中国药科大学ChinaPharmaceuticalUniversitystructuralsupport,catalysis,signalingandimmunefunctionenergyproductionandstructuralsupportenergystorage,cushioningandstructuralsupportstorageofgeneticinformationcarbonatomsarecovalentlybondedtogetherinverystablestructureshangofftheskeletonandparticipateinchemicalreactions中国药科大学ChinaPharmaceuticalUniversitysugarnucleicacidinheritedproteinsdeoxyribonucleicacidnucleotidespurinespyrimidinesdoublehelix中国药科大学ChinaPharmaceuticalUniversity中国药科大学ChinaPharmaceuticalUniversity1.Howdoesanenzymespeedupachemicalreaction?Anenzymespeedsupachemicalreactionbyloweringthereaction’sactivationenergy,thatis,theamountofenergyneededforthereactiontobegin.中国药科大学ChinaPharmaceuticalUniversity2.Whatistheactivesiteofanenzyme?Activesiteiswherethesubstratebindsandreal-timereactiontakesplace.Ithasspecificarrangementofaminoacidswhichrendersspecificsize,shapeandchemicalbehavior.Anenzyme’sactivesiteisuniqueonlytoaparticularsubstrate.中国药科大学ChinaPharmaceuticalUniversity3.Whatarethenon-proteinpartsofsomeenzymes?Manyenzymesconsistofanon-proteinpartcalled“Cofactor.”Cofactorsmaybe:cations,positivelychargedmetalions;activators,boundstemporarilytotheactivesitetoactivatetheenzyme;organicmolecules,vitaminsorvitaminproducts;coenzymesthatjoinenzymessubstratescomplextemporarily;prostheticgroups,permanentlyenzyme-bound.中国药科大学ChinaPharmaceuticalUniversity4.What’sthedifferencebetween“LockandKeyHypothesis”and“InducedFitHypothesis”?IntheLockandKeymodel,thesubstratesimplyfitsintotheactivesitetoformareactionintermediate,justlikethekeyfitsinitsspecificlock.Thereisnochangeintheirshapes.

InInducedFitmodel,theenzymechangesitsshapeuponbindingofsubstrateandthenbindsmoretightlytothesubstrate.中国药科大学ChinaPharmaceuticalUniversity5.HowdoenvironmentalfactorsliketemperatureandpHaffectenzymeactivity?Theoptimumtemperatureforenzymefunctionis37℃.Ahigherorlowertemperaturewillmaketheactivesitelesssuitedtobindsubstrate,thusdecreasingenzymeactivity.Hightemperaturecanevendenatureenzymes,makingthemlessactiveoreveninactive.Aminoacidspresentintheactivesiteareacidicorbasic.FluctuationinpHcanaffecttheseaminoacids,makingithardforsubstratestobind.ExtremepHvaluescanalsodenatureenzymes.中国药科大学ChinaPharmaceuticalUniversity6.Howdoenzymeinhibitorsinterferewithbiochemicalreactions?Competitiveinhibitorsoccupytheactivesiteandpreventasubstratemoleculefrombindingtotheenzyme.

Non-competitiveinhibitorsattachtopartoftheenzymeotherthantheactivesitetodistorttheshapeofanenzyme.中国药科大学ChinaPharmaceuticalUniversity

Vocabularyactivepharmaceuticalingredient活性药物成分generic[dʒəˈnerɪk]

仿制药brandnamedrug/originatorproduct品牌药、专利药、原研药ibuprofen[ˌaɪbjuːˈprəʊfen]

布洛芬osteoporosis[ˌɒstiəʊpəˈrəʊsɪs]骨质疏松multiplesclerosis[ˌmʌltɪplskləˈrəʊsɪs]多发性硬化tolerate[ˈtɒləreɪt]（对药物）耐受rheumatoidarthritis[ˌruːmətɔɪdɑːˈθraɪtɪs]类风湿性关节炎mastercellbank主细胞库（theprimarysourceofcellsforbiologicdrugs）Molecularweight:206.27中国药科大学ChinaPharmaceuticalUniversity中国药科大学ChinaPharmaceuticalUniversity1.Howdobiologicaldrugsdifferfromtraditionalchemicalmedicines?ComparisonBiologicaldrugs(e.g.monoclonalantibody)Traditionalchemicalmedicines(e.g.ibuprofen)RouteofadministrationMolecularsizeStructureManufacturing

injectionorinfusionoral(pill,tablet,orcapsule)largesmallsimplecomplexbiotechnologychemicalsynthesis中国药科大学ChinaPharmaceuticalUniversity2.Whycan’tbiosimilarsbemanufacturedidenticaltotheoriginatorproduct?Biosimilarsarebiologicdrugsthatarehighlysimilartoaparticularoriginatorbiologic,butnotthesame.Theproducingcelllineisdifferent.Themanufacturingprocessisdifferent.中国药科大学ChinaPharmaceuticalUniversity3.Whydoestheproductionofbiologicalmedicinesrequireahighlevelofmonitoringandtesting?Ahighlevelofmonitoringandtestingthroughouttheprocessisnecessaryforassuringthequalityandconsistencyinthefinalproduct.Ithelpsensurethateachdoseisbotheffectiveandsafeforpatients.Evenminorchangesinthemanufacturingprocesscanimpacthowthemedicineworksinthebody.Ithelpstotrackpossibledefectsinthemanufacturingprocessthatmaycauseadverseevents.

Vocabularyclusteredregularlyinterspacedshortpalindromicrepeats(CRISPER)成簇的规律间隔的短回文重复序列TheyareshortpalindromicrepeatingsequencesofDNAfoundinmostbacterialgenomesthatareinterruptedbyspacers—sequencesofgeneticcodederivedfromthegenomesofpreviouslyencounteredbacterialpathogens.analogue[ˈænəlɒɡ]相似物，类似的事情，类似物complex[ˈkɒmpleks]复合物sicklecellanemia[ˈsɪklseləˈniːmɪə]镰状细胞性贫血Huntington’sdisease亨廷顿舞蹈症off-target[ɒfˈtɑːɡɪt]脱靶中国药科大学ChinaPharmaceuticalUniversity中国药科大学ChinaPharmaceuticalUniversityTrueorFalse1.Whenvirusesinfectabacterium,thewholesequenceoftheirDNAwillbeinsertedintothechromosomeofthebacterium.2.TheCRISPRsystemcanonlyprotectbacteriafromvirusesforonegeneration.3.ItistheCas9componentoftheCRISPRsystemthatcutsuptheviralDNA.4.Whenadouble-strandedbreakinDNAisinducedbyCRISPRtechnologyinaplantorananimalcell,itcannolongerberepaired.5.ThespeakerthinksthatthefirstapplicationsoftheCRISPRtechnologyaregoingtohappeninthetreatmentofblooddisordersbecauseit’seasiertodeliverthesystemtobloodcellsthansolidtissuecells.6.TheCRISPRtechnologyhasbeensuccessfullyappliedindifferenttypesoftissuesandanimals.7.TherearestillsomechallengestoovercomebeforeclinicalapplicationoftheCRISPRtechnologybecomespossible.中国药科大学ChinaPharmaceuticalUniversity1.HowdoestheCRISPRsystemprotectbacteriaagainstviralinfection?DNAofinfectingvirusispluckedoutandinsertedinlittlebitsintoCRISPRsiteofbacterialchromosome;ThebitsofinsertedDNAaretranscribedintoRNA;ThoselittlebitsofRNAbindtoproteinscalledCas9toformacomplexthatsearchesthroughalloftheDNAinthecelltofindsiteswithmatchingsequences;

TheCas9cutuptheviralDNA.中国药科大学ChinaPharmaceuticalUniversity2.WhataretheadvantagesofCRISPRtechnologyoverpreviousgenomeengineeringtechnologies?----Oldertechnologieswereeitherinefficientortoodifficulttobeadoptedindifferentlaboratoriesorforclinicalapplications;----CRISPRtechnologyismuchsimpler.It’sjustlikesoftwareforthegenome,whichallowseasyprogrammingusingtheselittlebitsofRNA;中国药科大学ChinaPharmaceuticalUniversity3.ConsideringthecurrentprogressinCRISPRtechnology,whatdoyouthinkarethepossibleapplicationsofthistechnologyinmedicineandwhatarethepossiblerisks?Applications:Tomakeagenesilencedtostudyitsfunction;CRISPRsystemcanbedesignedtoinducecutandrepairatspecificsiteofthechromosome,makingitpossibletocorrectdisease-causingmutations;

ThefirstapplicationsoftheCRISPRtechnologyaregoingtohappeninthebloodwhereit’srelativelyeasiertodeliverthistoolintocellscomparedtosolidtissues;TocreatemodelsforhumandiseasePossiblerisks:DNAisnotrepairedintheintendedway;Off-targeteffect中国药科大学ChinaPharmaceuticalUniversity4.CRISPRtechnologyalsohasthepotentialtobeusedforenhancement,forexample,toengineerhumanstohavelesssusceptibilitytoacertaindisease,strongerbones,andevensmarterbrains.Areyoufororagainsttheapplicationofthistechnologyforthepurposeof“designerhumans”?Andwhy?ProsItisanewwaytobattlediseasesthatarechallenginganddeadly.Itcouldextendthelifespanofhumans.Itcouldbeawaytotreatgeneticdisorderedinthegeneralpopulation.Itwouldgiveparentsachancetogivetheirchildsomethingnew.Itcouldreduceissueswithsocietaldiscrimination.…ConsItofferssafetyconcernswhichwecannotignore.Itwouldreducethediversityofhumanity.Itcouldbeaviolationoftherightsofthechild.Itcouldenhancethesocioeconomicdifferencesinsociety.…中国药科大学ChinaPharmaceuticalUniversityAssignments:PartITask3InterpretationPartIITask3TheGoodandBadCholesterolPartIIITask1InsulinSignalingPathwayLectureFourPharmacologypharmacodynamicshistaminehypothalamuspermeabilitymembraneligandbioavailabilityendogenousacetylcholineendocytosisanyman-made,naturalorendogenoustheinteractionbetweenalivingorganismandchemicalsmoleculewhichexertsabiochemicalorphysiologicaleffectonthecell,tissue,organororganismhowalivingorganismaffectsthedrughowthedrugaffectstheorganismtherateandtheamountofadrugthatisabsorbedfromthegivendosageformandreachesthesystemiccirculationreleaseofdrugfrompharmaceuticalsimplediffusionsubstanceenteringthebloodcirculationthedispersionordisseminationofsubstancesthroughoutthefluidsandtissuestherecognitionbytheorganismthatformulationandpassthroughthemembranefacilitateddiffusionactivetransporttheroutethatadrugenterstheorganismitsbioavailabilityofthebodybiotransformationinactivationforeignsubstanceispresentinanirreversibletransformationofparentcompoundintodaughtermetabolitestheremovalofsubstancefromthebodysugarnucleicacidlockandkeyhydrophilicdeoxyribonucleicacidnicotinicsodiumgradientdepolarizationdimerizationautophosphorylationeffectortranscription

Vocabularyibuprofen[aɪbjuːˈprəʊfən]n.布洛芬snare[sneə(r)]vt.设陷阱捕获neutralize[ˈnjuːtrəlaɪz]vt.中和，使无效disintegrate[dɪsˈɪntɪɡreɪt]崩解metabolite[mɪˈtæbəˌlaɪt]代谢产物detach[dɪˈtætʃ]脱离，离开label[ˈleɪbl]标签sprained[spreɪnd]扭伤的unscathed[ʌnˈskeɪðd]

毫发无损的TrueorFalse1.Painkillersknowwherethepainisinthebodyandgettothelocationtorelievethepain.2.Apainkillerworksbypromotingtheproductionofcompoundsthatcanhelptotransmitpainsignals.3.Generally,itisbelievedthatthehigherthedose,themoreeffectivethedrug.4.Mostdrugmoleculeswillbefilteredoutbythekidneysintheurinewithoutundergoinganychanges.5.Foranydrugtakenorally,theyundergobasicallythesameprocessinthebody.6.Thedosinginstructionsonmedicinelabelscanrepresenteverypatient.7.Therearevariationsinthebody’sefficiencyofprocessingmedicineindifferentpatients,andthustheneedforpersonalizedtherapy.

1.Whenyouswallowapainkillerlikeibuprofen,howdoesitgetintothebloodcirculation?Andwhathappenswhendrugmoleculespassthroughtheliver?---Ibuprofendisintegratesintheacidicfluid.---Thedissolvedibuprofentravelsinthesmallintestineandcrosstheintestinalwallintothenetworkofbloodvessels.---Thesebloodvesselsfeedintoavein,whichcarriesthebloodtotheliver.---Drugmoleculespassthroughtheliver.---Theycontinuethejourneyoutoftheliver,throughveins,intothebodycirculatorysystem.---Whenthebloodanddrugmoleculesinittravelthroughliverbloodvessels,enzymesattempttoreactwithdrugmoleculestoneutralizethem.Thedamagedibuprofenmoleculescalledmetabolitesmaynolongerbeeffectiveaspainkillers.2.Howdoesthebodyeliminateibuprofen?Thebodystrikesefficientlyeliminatingibuprofen,withtheblooddosedecreasingbyhalfevery2hoursonaverage.Ibuprofenmoleculesdetachfromtheirtargetsandcarriedbythesystemicbloodstream.Eachtimewhenthedrugpassesthroughliver,asmallfractionofitgetstransformedintometabolitesandthenfilteredoutbythekidneys.Ineachloopfromlivertobodytothekidneys,alittlemoreofdrugisneutralizedandfilteredout.3.Whyisithardforchildrentogettherightdosage?That’sbecausehowtheyprocessthemedicinechangesquicklyasdotheirbodies.Thelevelofliverenzymesthatneutralizemedicationshighlyfluctuatesduringinfancyandchildhood.1.Whatisthefirst-passmetabolism?Drugstakenorallymaybemetabolizedbytheliverbeforetheyreachthesystemiccirculation.2.What’sthefunctionofcytochromeP450enzymesintheprocessofdrugmetabolism?CytochromeP450enzymesmetabolizedrugsthroughavarietyofprocesses.Theseincludeoxidation,hydrolysisandhydroxylation----ItishydoxylatedinphaseImetabolism;----Inphase2metabolism,,alargeglucuronicacidgroupisattachedtothedrugthroughtheactionofUDP-glucuronosyltransferase.Theglucuronicacidgrouphasmanypolargroupsattachedtoit,namely,threehydroxylgroupsandacarboxylgroup.Thismakesthemoleculeextremelywater-solubleorhydrophilic.Thusthedrugcanbeeasilyfilteredandexcretedbythekidneys.3.Howdoesthedrugmoleculebecomemorewater-solublesoitcanbeeasilyexcretedbykidneys?oxidation,reduction,hydrolysisconjugationAprodrugneedstobemetabolizedbeforeithasanyeffect.So,thetherapeuticeffectofthedrugdependsonitsmetabolites.Thephase1metabolismofaspirininvolvescytochromeP450hydrolyzingtheaspirinmoleculeandtheresultantproductissalicylicacid.SalicylicacidcanthenbeacteduponbyUDP-glucuronosyltransferasetoattachglucuronicacidgroupinplaceofhydroxylgroup.Thentheproductcanbeeasilyexcretedbykidneys.4.Whatisaprodrug?5.Whatistheprocessofaspirinmetabolism?

Vocabularyrepurpose[ˌriːˈpɜːpəs]重新调整用途cocktail[ˈkɒkteɪl]鸡尾酒polypharmacology多重药理学（aconceptwhereamoleculecaninteractwithtwoormoretargetssimultaneously）withdraw[wɪðˈdrɔː]撤回leprosy[ˈleprəsi]麻风病1.Whataretheadvantagesofdrugrepurposingstrategyovertraditionalnewdrugdevelopment?----Traditionalnewdrugdevelopmenttakesoveradecadeandbillionsofdollarstobringasuccessfuldrugtothemarketplace；----Drugrepurposingcanbypassalargeportionofthetimeandcostassociatedwi