Chapter 29 & 30 Notes - Lipid & Amino Acid Biochemistry PDF

Chapter 29 Notes Fatty acids are often subcomponents of amore complexlipid TAGSand Glycerophospholipids are both complex lipids comprisedof aglycerol backboneand 2fatty acyls...

Chapter 29 Notes Fatty acids are often subcomponents of amore complexlipid TAGSand Glycerophospholipids are both complex lipids comprisedof aglycerol backboneand 2fatty acyls TAGShave a 3rdfatty acyl and phospholipids have a head group Phosphatidate is a commonprecursorformedbyadding afattyneglstoaglycerol 3phosphate G s e canbeformedfromDHAPandphosphorylated gyrol trinyl glycerol synthesisiscompleted bytrinay gyrol synthase ontheendoplasmic reticulum thephosphate fromphosphatidategetshydrolysedanda 3ʳᵈ FA is added toformspecificphospholipids apolarheadgroup isneeded to a basephospholipidstructure head groups include inosital choline serineand ethanolamine either thehead group or thephosphatidatemustbe activatedforthestructuresto connect phosphatidate isactivatedbyCTP forming a CDP intermediate whichis drivenbyPP hydrolysis Allows serineorinositol to replaceCMPonmolecule of cholineor ethanolamine group throughthe hydrolysisofGTPintoGD theactivationofthealcoholhand addition requires viaPPhydrolysis diacylglycerol replaces CMP this pathway ismoreactive as choline andethanolaminearemoreabundant than serine andinosital phosphatidylcholine isthemostabundantphospholipidinmammals butitssynthesisis influencedbydietarycholinestatus ifcholinestoresareadequatephosphatidylcholinewillbe synthesized byactivatingcholine if thereis a choline deficiency phosphatidylcholinewillbesynthesizedbymethylating phosphatidylthanolamine w s adenosyl methionine dietarycholinerequirementsincreasewithpregnancy Excess cholesterol is a response to excess foodenergy substrates converted into acetylCoAwhichis then converted into cholesterol andenergy excess get cholesterol is primarily synthesized inthe liveralthough mosttissuesdohavetheabilityto synthesizesomecholeste onlystage 2 ofcholesterol synthesis occurs in thecytoplasmwhilestages 2and 3 occur in the endoplasmic reticulum Thefinalproductofstage 1 of cholesterolsynthesis is isopentery phosphateandtheprocessbeginswith3 acetyl CoA beingusedto make HMG CA Chapter 29 Notes HMGCoA reductase reducesHMGCoAintomevalonate andthisis consideredthecommitedstepof cholesterolsynthe Anactivated isoprene uses 3ATP to convert mevalonateintoisopentgepyrophosphate because HMGCoA reductase is theratelimitingenzyme itisthemaintarget fortherapydrugsaimingtore cholesterol levels stage 2 of cholesterol synthesis involves condensing isoprenes isopentyl pyrophosphate and dimethyl allyl pyrophosphate condense tobecomegeranylpyrophosphate allyl pyrophosphate dimethyl isan isomer of isopentylpyrophosphate Athirdisopentyl pyrophosphate is added to the structure to form a ISCfarnesyl pyrophosph 2 farnesyl pyrophosphate condense to form squalene 30carbons stage 3 of cholesterol synthesis cyclizessqualene through a chain reactionandformscanosterol NADPHintosqualeneepoxideandformsonH2O intheprocess squalene getsreducedby squaleneepoxidegetsfurther reducedinto a protosterol ention cations getoxidized into protosterol Lanosterol There are 19stepsthatconvertInnosterolinto cholesterol and a net releaseof HOOHand 2co ThesynthesisofHMG CoAreductase mrna is controlled bythesterol regulatory element bindingprotein SREBP thetransitionofthemrnaintoproteiniscontrolled by ofmevalonateanddietary cholesterol metabolites whencellular concentrations of cholesterol increase proteolytic degradation ofthereductaseoccurs ifthe reductase is phosphorylatedbyamp d ependent it kinase is renderedinactive SREBP isfoundintheER in associationwithsoapandwhencholesterollevelsfallscanescortsseem tothegolgicomp SREBPis proteolitically processed andactivated inthegolgicomplex Activated seeremoves tothenucleustostimulatereductase mrnasynthesis andis thereforeconsidered a transcription factor andtrinylglycerolsaretransported inthebloodintheformoflipoproteinparticles cholesterol consist of amonolayerof phospholipids withprotein componentsand hydrophobic lipids inside Theproteinessservetosolubilizethelipidsandtodirecttheparticlestospecifictargets onesterifiedcholesterol is found inthemonolayer and cholesterol ester is found inthecore theproportionofprotein in alipoproteindetermines itsdensity moreprotein greaterdensity densitycanbedecreased by increasing trincylgige.ro proportions Chapter 29 Notes chylomicron andVLDLdeliver trineyglycerols LDLdeliverscholesterolandHDLscavengeexcess cholesterol VLDL ion LDLandHDL areformed intheliver LDL delivers cholesterol to peripheraltissueswhere it enters thecell byreceptormediated endocytosis once in thecell LDL is hydrolyzed by lysosomes andLDLreceptors are recycled The absence of theLDLreceptor tends tofamilial Hypercholesterolemia andatherosclerosis cholesterolaccumulates in plasmaandentersbloodvessels andneighbouringtissues accumulation in bloodvessels blocksimpairsbloodflow CDLisn'tbrokendown property whichcausesit to becomeoxidized andingested by macrophages become foamcells synthesis ofcholesterol is upregulatedwhenit isremovedfromthediet there is evidencethatsaturatedfats cholesterol thanmuraandPuras synthesismore may upregulate simplecarbohydrates maybeworsethan saturated Fatsastheylead toexcessenergyand excessacetylCoa products cholesterol isanimportant precursorforbilesaltssteroidsandvitaminD Chapter 30 Notes Aminoacidsareformedfrom thedigestion of excessproteinsandfrom thedegradationofdefective or unneeded cellular proteins thebody cannotstore excessaminoacids sotheygetdegradedinto a carbonbackbonewithan amine go Amino t ransferases transferamine groupsfroman aminoacid to aketoglutarate togenerateglutamate Aspartate transaminase moves theaminegroupfromaspartate onto a ketoglutarate to form oxaloacetateandglo Alaninetransaminasemovestheamine fromalanineto a ketoglutarate toform pyruvate andglutamine group glutamateandrelease NHy Glutamate dehydrogenase canthen oxidatively deaminate someaminoacids canbedirectlydeaminated using a dehydratase serinebecomes pyruvateand NHT and threonine becomes aketo butyrate andwhat muscle canexportnitrogenfrombranched chainaminoacidsto theliver tobe processed groupadded to pyruvateforms Amine alaninewhileonaminegroup added toglutamateformsglutamin intoTcaintermediates carbons frombranchchainaminoacidsare converted in muscle toproduceenergy intheliver theamine group on alaninegetstransferred toglutamate forthe unencycle theurea cycle generates pyruvatethatenters gluconeogenesis Bloodlevelsof aminotransferase serve a diagnostic function to determineliverdamage if thecellmembranes of livercells are damaged proteins canleakintothebloodstream interrestrial vertebrates excess Nitat is convertedintounenandthis occurs in theliverinhumans orenformed fromNADHandwhatthatresultsfrom converting glutamateinto a ketoglutarate oven isthechosenstoragemolecule foraminegroups overammonia because itssoluble in waterhasneutralpoin andis nontoxic meaning itcanbestored biologically Ammonia is a volitisesmallmobile moleculethatwillaccept a protontoformammoniumandincreasebody the 2 nitrogenatoms in urea comefrom aspartate andammonia step 1 oftheovencyclecouplesammonia tobicarbonate and occurs inthemitochondria irreversible reaction is catalyzed by carbamoy phosphate synthetase Cese and requires 2 ATP key regulatoryenzyme Nacetylglutamate is an allostericactivator of CPS I and is formedbyacetylCoaandglutamatewhenthere an excess of aminoacids step2 ofovencycleforms citrullinefromornithine anda carbamoyl group  Chapter 30 Notes carbamolyase transfers thecarbonyl ornithine trans groupto ornithine getstransported outofthe inexchange forornithine citrustine mitochondria step 3 of ovencycle occurs in thecytoplasm andinvolves the condensation of citrullinewith aspartate formArginine succinate reactioncatalyzed byargininesuccinate synthetase anddrivenbytheconversion ofATP intoAMPand step4 of theureacycle cleavesarginine succinateintoarginineandfomerate vin Arginine succinase fumerate is a byproduct oforen cycle finalstepof ureacycle seesarginine cleaved intoureaand ornithinebyorganase get ornithine transferred backintothemitochondria torestartthecycle gets The 7 metabolic intermediatesformedfromominacids are pyruvate acetyl Coa nectoncety cA α ketoglutarate succinge ca fumarate and oxaloacetate acidsaremetabolizedintoacetylcoaand acetoncetyl CoA ketogenicamino The onlyentirely ketogenicaminoacidsare canformfats leucineandlysineandthey butnotglucose acids gluconeogmicamino aredegraded intopyruvate or TCAintermediates andthereforecanbeusedtomakeglucose acidsthatareboth ketogenicandgluconeogenichavecarbonstructuresthatcanbemetabolized Amino byeitherroute th also carbonstructurecan belargeenoughto providepartstobothroutes tryptophanphenylalanine tyrosine someaminoacidscanbe directly converted to intermediates by transamination Alanine topyruvate Aspartate tooxaloacetateand glutamate to ketoglutarate otheraminoacidsrequireotherstepstoform intermediates pyruvaterequires 3 carbonaminoacidsand 3carbonpieces oxaloacetate requires 4carbonaminoacids α ketoglutarate requires 5carbonaminoacidsands carbonpieces succinyl CoArequires nonpolar aminoacids AcetylCoaandAcetoacetate requirebranched chainamino acidsandpieces of aromatic aminoacids fumerate requires aspartate viatheureacycle andpieces of phenylalanine tyrosine Phenylketonuria Pku is oneofthefirstlinksbetweengeneticmutations biochemicalerrorsandpathology is ageneticmutationthatresultsin nonfunctional phenylalaninehydroxylasePAH whichphenylalanine tonotbe degradedproperly Chapter 30 Notes nondegraded upin tissuesandblood whichdisruptsbraingrowthandmetabolism phenylalanine builds pyruvategetsexcreted in urineandis a resultofanattempt of metabolism phenyl byremoving anaminegroup geneticscreeningofnewbornscandetectindividualswithPku canbetreatedusinglow phenylalaninediets Chapter 32 Notes thebasicstructureof a nucleotideiscomprisedofa heterocyclicnitrogenousbase a scarbonribosesugaranda prospante nitrogenousbase ringpyrimidine ora doubleringpurine iseitherasingle phosphatescan bemono ai or tri withoutthephosphate groupthe structureisconsidereda nucleoside ATPGTPCTPandOTP allhave a deoxynucleotide version of them deoxyversion ofUTP isTTP NADand FAD are alsonucleotides butareconsidereddinucleotide becausethey are comprisedof a linked nucleotides oneofFADnucleotides is linear demand fornucleotides canbehighin proliferatingcellsandcancercells inhibitnucleotidesynthesis manycancerdrugs nitrogenousbases canbesynthesized denovo fromscratch or usingexisting bases ribosesugarsareformedviathepentosephosphate pathways deoxyribonucleotides aremadefromribonucleotide Denovo andsalvageprocessesformaking nucleotidesbothrequire PRPP PRPPis a riboseactivated by a pyrophosphate whenpyrophosphateis removedthe energy released willbeusedtoattachanewbasetotheribose pyrimidines aresynthesized frombicarbonateaspartateandammonia thering is synthesized firstandthenattachedtoanactivatedribose end product is UMP step 1 of pyrimidine pathway combines bicarbandNH toformcarbamoylphosphate vinCPSII step 2 addsaspartate tocarbonylphosphate toform carbamoylosportate whichthengetscyclizedandoxidized formingorotate aspartate carbamoyl is formed byaspartatetranscarbamolyasewhichis thekey in the regulatoryenzyme pathway step3 combinesorotatewithPrep tojoinoritidgiate ome oritiaginte is convertedintoUMPbeforebeing converted intoUTP andothernucleotides Theenzymethatconverts up intoUDPis a onespecificnucleoside monophosphate kinase Chapter 32 Notes Nonspecificnucleosidediphosphate kinases convert UDPintoUTP CTPis formed byaminating Utp TTPis formed bymethylatingand reducingUTP Purines aresynthesizedontheribosemoleculeby S Pr 1 aminebeingformedfromPRPandglutamine reaction is catalyzed byglutamine phosphoribosyl aminotransferase IMP is thefinalproductofthepurinepathway AMP isformedfromIMP vin a pathwaythatrequires GTP GMPis formedfrom IMPvia a pathwayrequiring ATP once 5PR I amine is formedglycineisadded followedby a formylgroupfromformyl tetrahydrofolate Ammonia isaddednext whichstarts theformationofthesecondringwhich is closedbyATP co frombicarbonate isthenaddedto theamineofthesecondringandshiftedto aneighbouring carbon ontothenewcarboxyl added Aspartate isthen fumerate then leaves the structure leavingan aminegroup folate adds a secondfolate group gets closed bydehydrationformingIMP structure ring AMP is formedwhenan amine isaddedto IMPfromaspartate GMP isformed when IMP is hydrated andoxidizedinto MP whichthen receives an aminefromglutamineforming GMP ATPandGTPareformed beingaddedvin specific nucleosidemonophosphate kinases and additional phosphates by non specific diphosphate kinases deoxyribonucleotides aresynthesizedfrom ribonucleotidediphosphates vin a reduction reaction 2 hydroxygroup ofribose is replacedbya hydrogenbyribonucleotidereductase TMP is formedwhen dude isconvertedinto dump by kinase pyrophosphatase renationsandthenmethylated by thymidylatesynthetase process requires a carbongroupfrom folate inhibiting cell nucleotide synthesiscaninhibit growthwhichis thebasisfor chemotherapy Fluorouracilis a dumpanalogthat actsasa suicideinhibitor preventingtheformationof the AminopterinandMethotrexateare folateanalogsthatinhibitthe production ofa needed cofactor  in Chapter 33 Notes DNAwinding opercomingAdditional is pwapossesseserrordetectionanderrorrepairwhichallowsforgoodcopies tobemade him Tereosomes wrappedintospring Dnareplication is a semiconservative process while RNAevolves10x faster Further chromo andloopingofthe wrapping RNAhasnoerror detectionorrepairandtherefore results in flawedcopies matin a an anapane a.mnwherethe 3onofribosebindstonextnucleotide atthe Phosphate thephosphategroupsgiveDNA alargenegativechange DNAbasesareboundtogetherviahydrogenbondingwhichallowthemoleculetobeeasilyopened TheDNAbaseshavenochargeandarefoundin theinterior ofthehelixwhilethenegative phosphates areontheoutside DNAcanbefound in different formswhichcanaffectits expression Bformistheclassicformandmostcommon AformtendstoformwithdehydrationbutcommonwithDNARNAhybrids andRNARNAfolding 2 formisn'tcompletely understoodbutforms a lefthandedhelixinsteadof a right theglycosidicbondsinDNAarenotdiametricallyoppositeeachother hasa largerside thatformsa majorgrooveanda smallersidethatforms a minorgroove BothDNAgroovesarelinedwithpotentialhydrogenbonddonors andacceptors Nucleosomes areformedbyDNAwrappingaround positively charged histone proteins onemeans ofcombatingcanceristomodifyDnatopreventreplicationandtranscription Cisplatin is a chemotherapeuticagentthatreactswithDNA Nitrogens ofDNA purinesreplacethecisplatinchlorideatoms whichdisruptstheDNAstructure and preventsaccess by DNArepairenzymes results in celldeath stemLoopstructure is common in singlestrandDNAandRNA consists of a regionofcomplimentarysequence folded backon itself singlestrandDNAandRNAcanalsoformmore complicated structures usingwatsoncrickbasepairing additionalhydrogenbonding memetalionssuchasmagnesiumto stabilizethestructure  Chapter 34 Notes DNApolymerasecatalyzes replication 4 deoxy nucleoside triphosphate datedatedetPTTP and mgtarerequired ADNAtemplatestrandis used todirectDNAsynthesis AprimermadefromRNAbya primasemustbe present toallownewDnastrandtogrow DNApolymeraseneedsa 3 0Htoneed builds s to 3 ManyDNA polymeraseshavenucleasenetivitythatallowsfortheremovalofmismatchedbases Exonucleasesremovemismatches tomaintaingoodcopies im ainauaiatingowa I DNApolymerase I isinvolved in repairbutalsotheremovalreplacementoftheoriginal RNAprimer its exonverense works from s to3 Dnapolymerase isaHoloenzymethatcontains pans which is a helicasethatunwinds tocoil has a polymerase cores that make Dnastrands windingandunwinding ofDNA canchange supercoils topoisomerase sniprejoinDna toassist helicase unwindingandrestoresuperconsafterwards because DNApolymerase directionthelaggingstrandmustbebuitb ackwards only works in a s to 3 Dnapolymerase I forms okazakifragmentsthat jointogetherlaterusinga Dnaligaseenzyme toreplicatethelagging strand singlestrandbinding sso proteinmustfirststabilize it Primase thenmakes RnaprimersandDnapolymerase makes Dnausing looping trombone slide Dnapolymerase thenremovestheRnaprimerandfillsthegap finalstepis when Dnaligasejointhe DNAfragments During DNA replication everyokazaki fragment synthesized by Dna polymerase iselongatedfroma separate primer smallamountsof DNAcan be amplified using testtube replication process usedin biomedical andforensic testing thermal cycling is required becauseheatis needed toseparatethe strands breakhydrogen bonds I e.com DNApolymerasewasoriginally used butnowuse tae pol Chapter 34 Notes improper nucleotide insertion occurs when a nucleotidefailstohydrogen bondcorrectlywithtemplatestrand nuenotideflipsoutwardsfromthestrandand is detected sent to exonuclease wherethepieceis clearedoffandrestarted gets processslowsreplication butensuresgoodDNAcopies Thefreeends oflinearDNAmesusceptible todamage by exonucleases withthenature ofDna synthesis oneofthestrandsofDnawillshorten uponeachroundof synthesis telomeres arefoundontheendsofthechromosomes thelendingstrandis longerandrich inguanine whichallowstheDnatoform a loopstructureandprotecttheen ofthe chromosome Glomrateactivity is nowin mosthumancells andwhen telomeresgottooshort celldeath andagingoccurs the Grichlending strand ofthe telomerecanbemaintainedbytheenzyme telomerase telomerase contains an Rna template that it usestoextendthe landing strand in rapidly dividing cellsincludingcancercellstelomeres mustbemaintained bythe topreventshorten telomerase ofthelaggingstrandwhichwouldlead tocell death  Chapter 35 Notes lentmutationstillcodesforthesameaminoacid utralmutationcodes forverysimilaramino random change in nematodesequence canoccurdue to copyerrorsduringDNAreplication orfrom mutagenexposor ingtherisnochangetotheprotein acid codes ordifferent are or lightmaration certainchemicalsandviruses aswellasvin hypermutation whichiscell bythe p rocesses driven jeum utopian aminoauraand unsense mutation codesforstop m endingtheprom ge nucleotide polymorphism son canoccurinsomaticcellsandwon'tbepassedto descendants or germlinecellsandwillbepassedto descendents mess Ability to withstandenvironmentalstress DNArepairsystemsfollowthesamemechanisticoutline recognizetheinappropriate bases removethemrepair thegapwithDw canbespecific toan environment Alsotheabilitytosurvive toadulthood polymerase andirg.se repairthatis dependenton other polymerasesarenotas preciseasnormalreplicativeprocessesand mayintroduce mutations smallsomemutationsoccurat thelevelof nucleotides or a smallgone pointmutation isa singlenucleotide exchange thecanresult in asilentmutationneutralmutation missensemutation or nonsensemutation shiftorsplicesite from causingmajorchangestothe insertionmutationsinsertanextranucleotidewhichcauses mutation res gone protein deletionmutationsremove a nucleotidewhichalsoresultsin majorchanges germanesubstitution ofa singlenucleotide ispresentin it or moreofthepopulationandcanexplainhumanvariation in diseasem.sk andmetabolism noncodingsnpscanstillimpactexpressionprocessandhavehealtheffects codingSNPscanbesynonymous ornonsynonymous synonymoushaveno changeinaminoacidsbutmayimpact rateandpossibleprotein conformation translation Non synonymous areeither missense or nonsense mutations largescalemutationsseechangesin chromosomal structure whenasingle chromosome isaffected deceason duplication orinversion isthenose when a chromosomesareinvolveditscalled a juxtaposition insertiondeletionhas section a ofonechromosomegetinstantiaintoanotherchromosome translocation istheinterenanging ofpiecesof chromosome mutations canresultinlossorgainfunction lethal or reversion dominament negativemumaon has ageneproduct ofteninactive antagonizetheproduct of a normalallele inrespecttofitnessmutationsareconsideredneutralnearlyneutraldeleterious or advantageous COVID19infection rates monased duetomutations Chapters 36 and 37 synthesis ofRNAfroma DNAtemplate is catalyzed byRNA polymerase responsible for initiatingandelongatingtheRNAproductandgrowsinthe s to 3 direction withno Inggingstrand themRNA is transcriptedfromthetemplate antisense DNAstrandandcompliments its sequence the codingstrand ofDNAhasthesame sequenceasmrnajustwith insteadof u RNApolymerase requires a ribonucleosideemprospantes anddivalentmetalslike mg or must RNA polymerase I is found in thenucleolus transcribes rrna andis insensitive to a Amantinmushroomtoxin RNApolymerase is found in thenucleoplasm transcribes mRNAandsnRNA and is very sensitive to αAmant RNApolymerase II is found in thenucleoplasm transcribes trna and is only moderatelysensitive to a Aman rRNAis ribosomal RNAhas4 sizesand combineswith proteins toformribosomes tentshape withanticodon loopsformRNAandacceptorstemsforAA tRNAis transferRNAandis typicallyfoundina clover geneticsequence ofproteinsfromDNA mRNA is messengerRNAand isthe multicellular organisms usearterentialgeneregulation togeneratearrantcelltypes geneexpression in eukaryotes is by influenced complex transcription regulation Rna processingincluding extensive processing mRNAprecursors andthenuclearmembrane whichseparatesthesiteofRnasynthesisfromthatofproteinsynthesis prokaryoteshave no regulation of transcriptionandtranslation transcription consists of 3pursesinitiation elongation andtermination Initiation involvesthebinding of reparationmachinerytheRna polymerase andtranscriptionfactors to promoterregions Elongation istheformation ofthecomplementaryRnastance termination is therelease of RNA polymerase andthenewtranscript DNAsequencepromotorsexistatthestartpointofthe geneandsincetranscription factors considered therecognitionunitforpolymerase andisalwaysonthesamepieceofDnaasthegenebeing transcribed willvarydepending onthetypeof polymerase itcodesfor RNApolymerase promoters canbean upstream TATA box aninitiatorelementin atthe start a downstream a promoterelement DPE or upstream CAAT or GCboxes initiatore lementsare usuallypairedwitha TATAboxbutifthereisnotataboxwillwork in cooperationwithDPE GCboxis common in genesthatarecontinuously expressed Chapters 36 and 37 transcriptionfactors areproteinsthatbindtopromoterregionsto regulate transcription oncetranscriptionis completedtheydiffuseawayandrentelsewhere generaltranscriptionfactors formRNApolymerase complexes transcriptionfactors withFIA andTe B sequencespeciac transcriptionfactorsform sequence specific conotuntors or corepressors TATAboxbindingprotein top is a component ofTFIIDandbinds totheTATAbox forms a saddle thatother transcription factorsbindtoCTEa TF B.TT D TFIE TFIFTF H transcriptionfactorshavevariousproperties including helicaseAtpase kinase DNA bindingproteinproteinbinding RNApolymerase alsobinds to it TF A binding results in thephosphorylation ofthe polymerase which transitionsthestructure intotheelongate phase Enhancer sequences are DNAsequences butnotpromotersequencesthatcaninfluencethestrengthoftranscription by operatingin conjunctionwith bindingproteins called transcription activators enhancer position of thesequencevarieswidely andcanbe farawayfromthestartsite maybewhatmakeshumanshuman Haense gene enhancers howsevidence oflatehumanevolutionaftersplitwith chimpanzeemustorsandappearstobeinvolved human foot thumbevolution human accelerated regions area set of49segments ofthehumangenomethatwereconserved throughout vertebra evolution butare different in humans theirnamingorderindicates theirdegree of difference from chimpanzees most HARS don't codefor proteins and are mainlyfound in intron regions nearproteincodinggene transcription factors andDNAbinding proteins have roles as regulatory elements andRNAgene responseelements are monotidesequencesthatnowspecificstimulitocontrol gene expression canbesteroid hormones cyclicAMP IGF1 SREBP can bepart of promoters orenhancersandserve as binding sitesfor transcription factors Nuclear hormone receptorsbindto specific responseelements ofDNA have 4 highly conserved domainsAminoterminal activationdomain zincfingerDNAbindingdom hinge domains thatcontain a nuclear localization signaland ligandbindingdomain Chapters 36 and 37 Theaminoterminal activation domain enables the receptor to interact withotherproteins Theligandbindingdomainchanges structurewithligandbinding torecruitotherproteinstoregulate transcription nuclearhormone receptorscanalter transcription in 2 ways thecomplex ofreceptorandligandcanrecruitproteinscalled conctivatorsthatstimulate transcription in theunboundfoundsomereceptorsbindto compressorsandinhibit transcription ligandbindingthenreleasesthe compressors sotranscriptioncanoccur Histone acylation isanexampleof conctivatoractivity as thetransfer ofacetyl groupsontolysineresidues on nisto changes thepolarityof thehistonetobe neutral andthiscauses theDNAdissociatesfromuntone reversible process bydeacetylase  Chapter 38 changing theRNAaftertranscription involves cuttingandsplicingofRnaandtheinsertion deletionandsubstitution of nucleotides canbe influenced bytissuelocation ortime RNApolymerase I synthesizes a large precursor RNAcuss whichgetsprocessed toyieldiss28sands.gs rrna w and components ofthe ribosome RNApolymerase catalyzes the synthesisof precursors to tRNA nucleotides andribosesarealsomodifiedandanintronisremoved are removedfromthe s endaddedtothe3end bases ligatethefinalproduct RNApolymerase produces mrna mrna provisors pre Gtpis addedtothes andinanunusual s s lineage thatmayalsobe methylation whichformsthe s cap polyAtail 250nucleotideslong isneededtothe3 end noncoding stratenes ofRNAcalled introns noncodingareremovedandtheproducts codingare ligatedtoformmn mRNA Alternative splicing expandsproteindiversityfromthe DNAcoding s ame MRNA isprocesseddifferentlyaretoasignal Alternative string ornucleotide modification Chapter 39 Thegeneticcodelinks nucleic acidandaminoacidinformation characteristics ofgeneticcode are Three nucleotides calleda codon encode anamino acid Thecode is non overlappingandhasno punctuation code is madinthe 5 to 3 direction codeis degenerate in thatsomeaminoacidsareencoded bymorethanone codon nucleotide basescode for20 aminoneeds andthereare 64potential combinations 3 combinations code forstopcodons 61conoraminoacids TransferRNAtRNA moleculesfunction asanadaptormoleculebetween a codonandanaminoacid thereis atleastonetrna moleculeforeachaminoacid general characteristics ofERNA moleculesinclude asinglestrandofRnabetween73andas nucleotides inlength 3dimensio structure ofthemolecule is cshapedand unusualbasessoonas inosine orbasesthathavebeenmodified Alsoincludes cloverleafpattern in as withmanyofthenucleotideshydrogenbondtoformstemsandloops s terminal residue is usuallya phosphorylated PG Aminoacids get attachedto a hydroxylgroupofadenosine inthe3 Ccaregionoftheacceptorstem theanticodonisin a loopnearthecenterofthesequence theanticodonformsbasepairswiththecodonandbotharewrittenoutin thes tothe3 direction thanonecodonsincethereis sometriviamoleculescanrecognizemore onlysi trnamoleculesinhumansfor64totalcodons recognition ofthethirdbaseinthecodonbythe1stoftheanticodon is sometimesless discriminating andisknown wobble codonsthatdifferineither ofthefirsttwonucleotidesmustberecognizedbydifferentErna Thefirstbaseoftheanticodondetermines degreeofwobble 1 codon CtoG Atoo 2codons UtoA G Gto v orc 3 codons inosineto u c ora to activate an aminoacidAtptransfersprospaceonto anaminoacidforming aminoacylamp and Ppi aminoacyl trnasynthase joins aminoacylamp nagetrnaandAMP and trna togethertoform amino Eachaminoacyltrnasynthetase isspecificfora particularamino nardandaparticularErna Chapter 39 and40 enzyme specificity is dictated bydifferent featuresofeachaminonad typicallyuse an editing site to doublecheckforsimilaraminoacids siteofproteinsynthesisandsedimentsat70s ribosomesarethe madeof so and 30ssubunit ofits massis RNA isprotein ribosomal Rnaistheactualcatalystforproteinsynthesis 3 stepsof translation initiation is ribosome formation onmrna elongation builds theprimarystructureofproteinviapeptidebonds timinationputsa stopcodon on mrnareleasesthepolypeptideandribosome there are 3 tRNAbindingsiteson theribosome TheAsitebindstheincomingtRNA the psitebindstheErnawiththe growingpeptidechain theexitsitebinds theunchargedtrnabeforeit leavestheribosome TheacceptorendofthetrnasintheAsiteand Psitearenearoneanotheratasiteonthesossubmitwhere thepeptidebond formed a channel connectsthissitetothebackoftheribosomethroughwhichthepeptideexits prokaryote translation initiation begins when a 30s ribosome subunitbinds with IFI and IF andpreventspremature binding totheSossubunit 30s initiationcomplexisthenformedwhichconsistsof 2withGTPdeliveringformylmettrnatothemrnaalign correctly onthestartsequence 50ssubunitthenbindstothecomplexformingthe70scomplex bindsviaGTP hydrolysis byIF2 anddeparture oftheinitiationfactors formylmettRNAoccupiesthepsiteboundtotoAUGthereby establishing therendingframe prokaryoteelongationstarts bydelivering trnatothe Asitenexttothefinettrnain thePsite aminoacyl peptidebondforms b etween molecules elongationfactor a movesthemrnabyonecodonviaatphydrolysisandthiscausespeptidyltrnatomoveentirelytothe Psite leavingthe Asitevacant  Chapter 40 Notes Gene ApieceofDNAwitha proteinembedded elongation occurs untila stopcodonappears inthe Asite unitthatproducesproduct transcription but allprocessingstep includesDNA also stopcodonsin prokaryotesarerecognized by proteinscalled releasefactors RF instanceof trna RFfacilitatesrelease oftrmsintedproteinfromthePsite theribosomemRNAandtrnadissociate eukaryotetranslation is similar to prokaryote transmoonbutthe ribosomesarelarger 40sand60s toform80s proteinsynthesisbeginswithmethionineinstance offormylmethionine andaspecialinitiatorcalledmettrna is require theinitiatorcodonisalwaysthefirstAvafromthes endofthemrna moreproteininitiationfactorsarerequired mrna is circular areto interactions between proteinsthatbindthe s copandthosethatbindthepolyatail in eukaryotes proteinsynthesis occurs in thecytoplasmwhileRna synthesis occursinthenucleus posttranslationtheprotein sequencemustfoldproperlyandthiscanbeguidedbychaperoneproteins theycanthenbe directed tospecific organelles or modifiedintoother structures