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中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversityLectureThreeBiochemistry中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversityholoenzymelocuscatalystkinasedeoxyribose中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversityplaque
geneticsbiologictriglycerideautophosphorylation中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversityacaseofemergentproperties3Dstructure-basedfunction中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversitystructuralsupport,catalysis,signalingandimmunefunctionenergyproductionandstructuralsupportenergystorage,cushioningandstructuralsupportstorageofgeneticinformationcarbonatomsarecovalentlybondedtogetherinverystablestructureshangofftheskeletonandparticipateinchemicalreactions中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversitysugarnucleicacidinheritedproteinsdeoxyribonucleicacidnucleotidespurinespyrimidinesdoublehelix中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity1.Howdoesanenzymespeedupachemicalreaction?Anenzymespeedsupachemicalreactionbyloweringthereaction’sactivationenergy,thatis,theamountofenergyneededforthereactiontobegin.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity2.Whatistheactivesiteofanenzyme?Activesiteiswherethesubstratebindsandreal-timereactiontakesplace.Ithasspecificarrangementofaminoacidswhichrendersspecificsize,shapeandchemicalbehavior.Anenzyme’sactivesiteisuniqueonlytoaparticularsubstrate.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity3.Whatarethenon-proteinpartsofsomeenzymes?Manyenzymesconsistofanon-proteinpartcalled“Cofactor.”Cofactorsmaybe:cations,positivelychargedmetalions;activators,boundstemporarilytotheactivesitetoactivatetheenzyme;organicmolecules,vitaminsorvitaminproducts;coenzymesthatjoinenzymessubstratescomplextemporarily;prostheticgroups,permanentlyenzyme-bound.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity4.What’sthedifferencebetween“LockandKeyHypothesis”and“InducedFitHypothesis”?IntheLockandKeymodel,thesubstratesimplyfitsintotheactivesitetoformareactionintermediate,justlikethekeyfitsinitsspecificlock.Thereisnochangeintheirshapes.
InInducedFitmodel,theenzymechangesitsshapeuponbindingofsubstrateandthenbindsmoretightlytothesubstrate.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity5.HowdoenvironmentalfactorsliketemperatureandpHaffectenzymeactivity?Theoptimumtemperatureforenzymefunctionis37℃.Ahigherorlowertemperaturewillmaketheactivesitelesssuitedtobindsubstrate,thusdecreasingenzymeactivity.Hightemperaturecanevendenatureenzymes,makingthemlessactiveoreveninactive.Aminoacidspresentintheactivesiteareacidicorbasic.FluctuationinpHcanaffecttheseaminoacids,makingithardforsubstratestobind.ExtremepHvaluescanalsodenatureenzymes.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity6.Howdoenzymeinhibitorsinterferewithbiochemicalreactions?Competitiveinhibitorsoccupytheactivesiteandpreventasubstratemoleculefrombindingtotheenzyme.
Non-competitiveinhibitorsattachtopartoftheenzymeotherthantheactivesitetodistorttheshapeofanenzyme.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity
Vocabularyactivepharmaceuticalingredient活性藥物成分generic[d???ner?k]
仿制藥brandnamedrug/originatorproduct品牌藥、專(zhuān)利藥、原研藥ibuprofen[?a?bju??pr??fen]
布洛芬osteoporosis[??sti??p??r??s?s]骨質(zhì)疏松multiplesclerosis[?m?lt?plskl??r??s?s]多發(fā)性硬化tolerate[?t?l?re?t](對(duì)藥物)耐受rheumatoidarthritis[?ru?m?t??dɑ??θra?t?s]類(lèi)風(fēng)濕性關(guān)節(jié)炎mastercellbank主細(xì)胞庫(kù)(theprimarysourceofcellsforbiologicdrugs)Molecularweight:206.27中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity1.Howdobiologicaldrugsdifferfromtraditionalchemicalmedicines?ComparisonBiologicaldrugs(e.g.monoclonalantibody)Traditionalchemicalmedicines(e.g.ibuprofen)RouteofadministrationMolecularsizeStructureManufacturing
injectionorinfusionoral(pill,tablet,orcapsule)largesmallsimplecomplexbiotechnologychemicalsynthesis中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity2.Whycan’tbiosimilarsbemanufacturedidenticaltotheoriginatorproduct?Biosimilarsarebiologicdrugsthatarehighlysimilartoaparticularoriginatorbiologic,butnotthesame.Theproducingcelllineisdifferent.Themanufacturingprocessisdifferent.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity3.Whydoestheproductionofbiologicalmedicinesrequireahighlevelofmonitoringandtesting?Ahighlevelofmonitoringandtestingthroughouttheprocessisnecessaryforassuringthequalityandconsistencyinthefinalproduct.Ithelpsensurethateachdoseisbotheffectiveandsafeforpatients.Evenminorchangesinthemanufacturingprocesscanimpacthowthemedicineworksinthebody.Ithelpstotrackpossibledefectsinthemanufacturingprocessthatmaycauseadverseevents.
Vocabularyclusteredregularlyinterspacedshortpalindromicrepeats(CRISPER)成簇的規(guī)律間隔的短回文重復(fù)序列TheyareshortpalindromicrepeatingsequencesofDNAfoundinmostbacterialgenomesthatareinterruptedbyspacers—sequencesofgeneticcodederivedfromthegenomesofpreviouslyencounteredbacterialpathogens.analogue[??n?l?ɡ]相似物,類(lèi)似的事情,類(lèi)似物complex[?k?mpleks]復(fù)合物sicklecellanemia[?s?klsel??ni?m??]鐮狀細(xì)胞性貧血Huntington’sdisease亨廷頓舞蹈癥off-target[?f?tɑ?ɡ?t]脫靶中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversityTrueorFalse1.Whenvirusesinfectabacterium,thewholesequenceoftheirDNAwillbeinsertedintothechromosomeofthebacterium.2.TheCRISPRsystemcanonlyprotectbacteriafromvirusesforonegeneration.3.ItistheCas9componentoftheCRISPRsystemthatcutsuptheviralDNA.4.Whenadouble-strandedbreakinDNAisinducedbyCRISPRtechnologyinaplantorananimalcell,itcannolongerberepaired.5.ThespeakerthinksthatthefirstapplicationsoftheCRISPRtechnologyaregoingtohappeninthetreatmentofblooddisordersbecauseit’seasiertodeliverthesystemtobloodcellsthansolidtissuecells.6.TheCRISPRtechnologyhasbeensuccessfullyappliedindifferenttypesoftissuesandanimals.7.TherearestillsomechallengestoovercomebeforeclinicalapplicationoftheCRISPRtechnologybecomespossible.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity1.HowdoestheCRISPRsystemprotectbacteriaagainstviralinfection?DNAofinfectingvirusispluckedoutandinsertedinlittlebitsintoCRISPRsiteofbacterialchromosome;ThebitsofinsertedDNAaretranscribedintoRNA;ThoselittlebitsofRNAbindtoproteinscalledCas9toformacomplexthatsearchesthroughalloftheDNAinthecelltofindsiteswithmatchingsequences;
TheCas9cutuptheviralDNA.中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity2.WhataretheadvantagesofCRISPRtechnologyoverpreviousgenomeengineeringtechnologies?----Oldertechnologieswereeitherinefficientortoodifficulttobeadoptedindifferentlaboratoriesorforclinicalapplications;----CRISPRtechnologyismuchsimpler.It’sjustlikesoftwareforthegenome,whichallowseasyprogrammingusingtheselittlebitsofRNA;中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity3.ConsideringthecurrentprogressinCRISPRtechnology,whatdoyouthinkarethepossibleapplicationsofthistechnologyinmedicineandwhatarethepossiblerisks?Applications:Tomakeagenesilencedtostudyitsfunction;CRISPRsystemcanbedesignedtoinducecutandrepairatspecificsiteofthechromosome,makingitpossibletocorrectdisease-causingmutations;
ThefirstapplicationsoftheCRISPRtechnologyaregoingtohappeninthebloodwhereit’srelativelyeasiertodeliverthistoolintocellscomparedtosolidtissues;TocreatemodelsforhumandiseasePossiblerisks:DNAisnotrepairedintheintendedway;Off-targeteffect中國(guó)藥科大學(xué)ChinaPharmaceuticalUniversity4.CRISPRtechnologyalsohasthepotentialtobeusedforenhancement,forexample,toengineerhumanstohavelesssusce
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