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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,toengineerhumanstohavelesssusce

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