bioCHEMISTRY480MolecularBiochemistry--TheMacromoleculesSpring2017
Dr.JeffCorkill
SCI232Telephone359-6518Email:[email protected]
Textbook:
FundamentalsofBiochemistrybyVoet,VoetandPratt5thEd
OfficeHours:
Daily9:30am-10:30amdaily,MW2-3pmorbyappointment
ReferenceBooks:
Biochemistry,Voet,Voet&Pratt,4/EOnreserveInJFKLibrary
InadditionintheQP500-600SectionofJFKLibrary[lowerright
handbackcorner]thereisawidevarietyofbiochemistrybooks.Someoftheseare
generalundergraduatetextbookswhereasmanyothersdealwithspecialtopics(Adams
etal.,Kornberg,Baldwin,Orten&Newhaus,etc.).Makeanefforttocheckoutthisarea!
ClinicalchemistrybooksareundertheRAandRBheading.
InteractiveConceptsofBiochemistry:R.Boyer;Animations,conceptreviews,weblinks,
quizzes,cuttingedgeresearchreviews,etc.
RasMol:molecularmodelingfreewareprogramwillbeusedtoprepareanindividual
bioinformaticsweb-baseddocumentonaspecificenzymeprotein.Rawdatacanbe
manipulated/renderedintostructuralrepresentationsoftheproteins.Web-based
searchforproteinandDNAsequencedatawillbeobtainedandhomologoussequences
examined.
Homepage:https://sites.ewu.edu/jcorkill/home/
ThenclickonBiochemistry480:Thesubsectionsofthispageare:(1)480
Ramachandran’sBlog(2)ReviewandLectureNotes,Reviewofcourse,overall
biochemistryaims,metabolicpathwayschart(3)Keystoprevious480Autumn2016
tests,(4)Learningtargets,(5)KeystoSpring2017tests,quizzes,homework,(6)
Biochemistrywebsites,(6)Bioinformatics
CourseApproach:
Thiscoursewillstudythechemicalprinciplesofstructureand
interactionsofchemicalspeciesthatpertaintobiochemicalsystemsandthenattempt
toexplainthesystemsthemselves.Thecourseisorganisedsoastoencourageanatural
transitionfromorganicchemistrytobiochemistry.
Themajorthemeis
the3DStructure->(re)Activityinvivo->biologicalFunction’relationship(“SAF”).
Thetextbook(‘Voet’)hasbeenchosenforallofEWU’s
biochemistrycourses(CHEM480,481&482)collaborativelybyDrs.JeffCorkill,Nick
Burgess&JanelleJenkinstoreinforcethistheme.Thisassumesthatreactionswhich
occurinnatureareonly"variationsonatheme"ofthosewhicharefound(andyouhave
studied!)inorganicchemistry.Thefactorsthatcontroland/orinfluence"organic"
reactionsinvitroareanalogoustothosefoundinnature-invivo.Itisassumed(no!demanded!)thatstudentswillhaveaworkingknowledgeoforganicchemistry
especiallyfrommechanisticandenergeticsaspects(that’swhyCHEM352isaprerequisiteandwhyagradeof>2.0ispreferred!!).
Pre-requisites:
Thefollowingaretopicsofwhichyouareassumedtobefamiliar
withforthis400-levelbiochemistrycoursefromyourpreviousstudies:
(a)Factorswhichinfluencereactivity--electronicfactors(inductiveandresonance
effects),sterichindrance,solvent,pH,ionicstrength,temperature,catalysts,etc.
(b)Factorswhichinfluencebothinter-andintra-molecularinteractions(ionicattraction
andrepulsion,ion-dipole,hydrogenbonding,dipolarattraction,Londondispersion
forces[called‘hydrophobicinteractions’whenwateristhesolventasinlifeonEarth]
(c)Mechanismsinorganicreactions:
(i)Nucleophilicsubstitutionat>C=Oand>P=O(reactionsofamides,esters,phosphate
esters,carboxylicacidsandcarboxylateanions)CHEM352especiallyBruiceChapter16
(ii)Nucleophilicadditionat>C=O(reactionsofaldehydes&ketones)CHEM353oryou
willneedtoreadforunderstandingBruiceChapter17(see(iii)and(iv)below.
andtoamuchlesserdegree:(iii)Eliminationreactionsatsaturatedcarbon(E1,E2)(iv)
Electrophilicadditionat>C=C<CHEM351-2
ITISESPECIALLYIMPORTANTTOUNDERSTANDTHECHEMISTRYOF
(1) CARBOXYLICACIDS,ESTERSANDAMIDES&(2)SACCHARIDES
Memorise:
(i)
ACID+ALCOHOL=ESTER+WATER(andreversebyhydrolysis!!!)
(ii)
ACID+AMINE=AMIDE+WATER(andreversebyhydrolysis!!!)
(iii)
ALDEHYDE/KETONE+ALCOHOL=HEMIACETALthen+anotherALCOHOL>ACETAL(andreversebyhydrolysis!!!)
(iv)
ALDEHYDE/KETONE+primaryAMINE=IMINE(andreversebyhydrolysis!!!)
(d)Kinetics-orderofreaction,rateconstants,reactionprofiles,transitionstates,
intermediates, ΔG‡, ΔH‡, ΔS‡,andtheconceptoftransitionstates,etc.
(e)Equilibria-equilibriumconstants,positionofequilibria,endo-andexogonicreactions,
ΔGo,ΔHo,ENTROPYΔSoetc.
Alistof"Learningtargets"foreachtestwillbepostedonthe
websiteseveraldaysbeforeeachtest&willbediscussedthedaybeforeeachtest.
Youshouldbeawarethat,instudyingbiochemistryinamanner
describedabove,answerstoquestionsontestsandhomeworkwillconsequentlyhave
wtobeapproachedfromamolecularbiochemicalangleandnotabiologicalone.
BiologicalanswerswillgetlittlecreditandtypicallyaredB!Further,itisimportantto
answerthequestionaskednotanotherquestionofyourchoice(avoidtheremark‘true
butnottheanswertothisquestiononyourpaper)
Homework:
Therewillbesomehandedoutasproblemsets.Theyare
intendedtobepracticeforthenexttest.Theywillnotbeallgradedbutkeyswillbe
postedonthewebsite.Inaddition,therewillbeonlinehomeworkfromtheOpen
LearningInitiative(‘OLI’)sponsoredbytheCarnegie-MellonUniversity.Thesecanbe
accessedviahttps://oli.cmu.eduThecoursekeyis480Spr17andthecoursepasswordis
VVP5YouneedtoselfenrollattheURLabove;notehttpS.Allofthosespecifically
assignedwillcountfor15%ofoverallgradeifyoudothemontime!.
Quizzes:
Thesewillcovertheassignedpre-classmaterialandmaybeboth
individualandgroupinform.Someoftheassignedreadingwillbefrom(1)thetextbook
(2)researchpapersand(3)theSciencesectionofthe
.A
discussionofthequestionswillfollow.Thiswillmeanmorelearningonyourownand
lesslecturinginordertoachievemasteryofthetopic(s).Thesewillcountfor15%of
overallgrade.Nomakeups! Grades:
Therewillbefour"hourly"testson(tentatively):
#1Wednesday19thApril,#2Friday5thMay,#3Monday22ndMay,
&#4Tuesday6thJune
The4testscoreswillcountfor40%ofthegrade(thereareNOmake-ups).30%willbederived
fromquizzesandhomework.Anindividualbioinformaticsprojectonenzymestructurewill
count5%.Acomprehensivefinal(Thursday15thJune@10:30am)willcount25%
ThereareNOpointsforattendance(butit'srecommended!)
Yourgradeisdeterminedfromyouraveragescore(%)andDr.EvaExcel,i.e.
CourseGrade=(2.25x10-1[%])-(1.1x10-3[%]2)-7.10
i.e.anA-(3.7)is>77.5%,aB-(2.7)is>63%,aC-(1.7)>53%,aD-(>0.7)>45%(&<45%
fails.)Agraphof%versusgradeisonthe480webunderLectureNotesandintheblog.
EthicsandManners:Beawareoftheconsequencesofyouractiononotherstudentsin
thecourse.Turnoffthenoisemakerofcell‘phonesandORELSE!ANDTHATMEANS
NOTEXTING/CELLPHONEUSEINTHELECTUREROOM.Violatorswill
befirstwarnedafterwhichgradeswillbelowered.Ifyouknowacall/textmayarrive
duringclass,usethevibratemodeandsitnearthedoorandleave.NOCHEATING!
CURRICULUM(referencedtoVoet,Voet&Pratt5thEd.)
1.OverviewReviewofBiochemistry(onwebsite)&Chapters1&2
(a)naturallyoccurringcompoundsoflivingmatte
(b)organizationinlivingorganisms
(c)structure--activity--functionsrelationships
(d)interandintra-molecularbonding
(e)pH,ionizedspeciesandbuffers
(f)bio-energetics:thermodynamicsoflivingorganisms
2.TheChemistry,BiologicalStructureandFunctionsofAminoAcids&
Proteins[Chapters4,5,6&7]
(a) aminoacids
(b)proteins:structure/activity/biologicalfunction
(c)primary,secondary,tertiaryandquaternarystructureofpolypeptides
andproteins
(d)conformations,proteinfoldingandthermodynamics
(e)oxygen-transportingproteins,allosterism&cooperability,
(f)experimentalbiochemistry:chromatographyandelectrophoresis
3.Glycochemistry:TheSaccharides:Structure/activity/biological
functionrelationships[Chapter8]
(a)mono-saccharides
(b)di-saccharides
(c)oligo--saccharides
(d)poly--saccharides
(e)glycoproteinsandproteoglycans
4.Lipids,Cholesterolmetabolism,BiologicalMembranes&Membrane
Transport[parts][Chapters9,10&partsof20]
(a)structure&functionoflipids
(b)transportandmetabolismofcholesterolandtriglycerides
(c)structureandfunctionofmembranes
5.Enzymology[Chapters11&12]
(a)Bio-molecularmechanisms,
(b)Michaelis-Mentenkinetics,and
(c)regulationinvivo
6.Nucleotides,DNA&RNAandRecombinantDNA[Chapter3]
(a)nucleotides&nucleicacidstructure(DNAandRNA)
(b)nucleotidesrolesofnucleicacids(DNAandRNA)
(c)the'CentralDogma',
(d)structuralanalysisofnucleicacids(‘sequencing’)
(e)epigenetics,genomicsandbioinformatics