metabolism - blueprint prep · introduction hi, i’m phil! u mcat content writer u tutored and...

Metabolism

Today’s Info Session

u  Welcome to this Info Session!

u  Introduction

u  Glycolysis

u  Kreb’s cycle

u  Electron transport chain

u  Practice passage

u  How Can Next Step Help?

u  Questions?

WHAT IS YOUR NEXT STEP?

Introduction

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u  MCAT Content writer

u  Tutored and taught for 9+ years

u  Attended University of Nebraska Medical Center as an MD/PhD student.

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BiochemStudyStrategies

OfficeHours:BiochemContentReview

Recurringthemeforbiochem:

Don’tmisstheforestforthetrees!

Adaptedfromquinn.anyaunderCCBY-SA2.0

Whenstudying,askyourself…

•  Whydoesthismatterphysiologically?

•  Whataretheinputs&outputsofa

pathway?

•  Biomolecules:howdoeschemical

structureconnecttobiologicalfunction?

•  Pathways:whatdoesapathwayDO?

•  Howisapathwayregulated(big-picture?)

•  Doesapathwayhaveanyespeciallyimportantsteps?

BiochemStudyStrategies


Abig-pictureapproachtobiochem:

HowisbiochemtestedontheMCAT?How

doyougetthemostbangforyourbuckin

termsofstudying?

Focuson:

•  Principles

•  Physiologicalfunction

•  Interconnectionswithothersubjectmatter

Aminoacids&acid-basechemistry

Carbohydrates&stereochemistry

Metabolism&physiology

Glycolysis

•  Breakdownofglucoseintopyruvate•  NetATPproduction:2molecules

•  2NADHmoleculesarealsoproduced

•  Anaerobic

•  Productsfedinto….•  Citricacidcycle

•  Fermentation

•  Occursincytosol

C6H12O6+2NAD++2ADP+2Pi→2pyruvate+2NADH+2H++2ATP+2H2O

•  Tightlyregulatedtoavoidfutilecyclewithgluconeogenesis


Glycolysis

•  Input:Steps1-5

•  Output:Steps6-10

ImageadaptedfromThomasShafeeunderCCBY-SA4.0

•  ATPinput:Steps1,3

•  ATPoutput:Steps7,10

•  Regulatorypoints:

•  Step1(hexokinase)

•  Step3(phosphofructokinase[PFK])

•  Step10(pyruvatekinase)

•  Committedstep:Step3

•  PFK1inhibitedby↑ATP,↓

pH,and↑PEP(adownstream

product)

•  PFK1activatedby↑AMPand

fructose2,6-bisphosphate

•  Rateofglycolysis

•  ↑when[ATP]islow

•  ↓when[ATP]ishigh


Kinases-addsphosophate

Phosphatases=RemoveP!

Phosphorylases–Addsphosphate!

Gluconeogenesis

•  Creationofglucosefrompyruvate,lactate,glycerol(lipids),someAAs

mitochondria

cytosol

•  Occursmainlyinliver(+cortexofkidneys).

•  Differentfromglycolysisin3majorsteps

•  Ifnot“bypassed”wouldbehighlyendergonic.

•  Fastingconditionspromotegluconeogenesis

•  Acetyl-CoA(frombeta-oxidation):↑gluconeogenesis

•  Glucagonàinhibitsglycolyticenzymes,promotesPEPCKà↑gluconeogenesis

•  High[AMP]promotesgluconeogenesis.

•  High[ATP]inhibitsgluconeogenesis.


Glycolysis&Gluconeogenesis

1.Allofthefollowingaretrueaboutglycolysis

EXCEPTthat:

A)itoccursinthecytoplasm.

B)itisananaerobicprocess.

C)itresultsinanetproductionof4ATP.

D)itrequiresATPinordertobeinitiated.

2.Anaerobicorganismisplacedinanoxygen-poor

environmentandbeginstoproduce:

A)anexcessofacetyl-CoA.

B)anexcessofNADH.

C)anexcessofATP.

D)anexcessofADP.


Glycolysis&Gluconeogenesis

3.Ofthefollowing,whichaccuratelydescribes

adifferencebetweenglycolysisand

gluconeogenesis?

A)Glycolysiscanoccurinallcells,while

gluconeogenesiscannot.

B)Glycolysisandgluconeogenesisoccurin

differentpartsofthecell.

C)OnlygluconeogenesisrequiresATPto

function.

D)Glycolysiscanoccurintheabsenceof

oxygen,whilegluconeogenesiscannot.

4.Theendgoalofgluconeogenesisisthe:

A)formationofacetyl-CoAforuseinthecitric

acidcycle.

B)creationofATPtofacilitatethecontinuation

ofbiologicalprocesses.

C)regenerationofNAD+toallowglycolysisto

continue.

D)regulationofbloodglucoselevels.

5.Elevatedlevelsofwhichsubstratewillstimulate

gluconeogenesis?

A)ADP

B)AMP

C)Acetyl-CoA

D)Glucose


KrebsCycle

•  IndirectlyproducesmanyATP.•  3NADH,1FADH2,1GTP

ImageadaptedfromYassineMrabetunderCCBY-SA3.0

•  Cannotproceedanaerobically,BUTdoesnotdirectlyrequireO2:why?

•  Occursinmitochondria.

•  Pyruvateàacetyl-CoAoccursviathePDC•  Acetyl-CoAßpyruvate,fattyacids,ketogenicAAs,etc.

•  Irreversiblesteps:

1.Acetyl-CoA+oxaloacetate+H2O→citrate+CoA-SH

2C 4C 6C

3.Isocitrate+NAD+→α-ketoglutarate+NADH+CO2(rate-limitingstep!)6C 5C

4.α-ketoglutarate+NAD++CoA-SH→succinyl-coA+NADH+CO2

5C 4C


KrebsCycle

•  Notthermodynamicallyfavorable:whydoesitproceed?

•  Finalstep:L-malate+NAD+→oxaloacetate+NADH+H+

•  NoteapplicationofLeChâtelier’sPrinciple&connectiontoGenChem!

•  Regulatedat4majorpoints:

•  AtthePDC(upsteamofcycleitself)

↑ATP,NADH,acetyl-CoAàPDKinactivatespyruvatedehydrogenaseà↓Krebscycle

•  Step1:inhibitedbycitrate[directproduct],ATP,NADH

•  Step3:inhibitedbysuccinyl-CoAandNADH[products],ATP

•  Step4:inhibitedbysuccinyl-CoA,NADH,ATP

Basicprinciple:negativefeedback!


KrebsCycle

6.DuringtheKrebscycle,isocitrateandNAD+

cometogethertoformalpha-ketoglutarate,

NADHandH+.Whichofthefollowingdescribe

thistypeofchemicalreaction?

A)Dehydration

B)Hydration

C)Decarboxylation

D)Oxidation

7.IntheKrebscycle,NAD+andFADreactwith

substratestoformNADHandFADH2.Over

thesameperiodoftimethatninemoleculesof

FADH2areproduced,howmanyunitsofNADH

willbesynthesized?

A)9molecules

B)18molecules

C)27molecules

D)36molecules


KrebsCycle

8.Passageofonemoleculeofpyruvatethrough

theKrebscycleyieldshowmanymolecules

ofATPwhenfollowedthroughoxidative

phosphorylation?

A)13

B)15

C)30

D)36

9.Highlevelsofwhichmoleculewillinhibitthe

TCAcycle?

A)AMP

B)ADP

C)NADH

D)NAD


Electrontransportchain

2pathwaysactually!

-  OneforNADH

-  OneforFADH2

ImageadaptedfromFvasconcellos[PublicDomain]


Generalinformation:

•  Occursalonginnermitochondrialmembrane

lowerreductionpotential

higherreductionpotential

terminalelectron

acceptor


•  ProvidesenergyforATPsynthase(protongradient)

•  ~30ATPperglucose

Mechanism:

•  4membrane-boundcomplexestransfere-fromNADHand

FADH2andpumpH+intointermembranespace

•  [H+]intermembranespace>[H+]matrix

•  Protonsrushdowngradient,poweringATPsynthase

Regulation:

•  Inhibitedby↓O2,↓[ADP]/[ATP],↓NADH

•  Stimulatedby↑O2,↑[ADP]/[ATP],↑NADH

Othermetabolicpathways

Glycogenesis

Glycogenolysis

Betaoxidationoffattyacids

Pentosephosphatepathway


TurnsglucoseintopentosesandNADPH

Breaksdownglycogen

Breaksdownfats

Buildsglycogen


10.Whichofthesestatementsregardingproton

pumpingisaccurate?

A)Theintermembranespacebecomespositive

duetotheprotonsbeingpumpedintoit.

B)Themitochondrialmatrixbecomespositive

duetotheprotonsbeingpumpedoutofit.

C)Theintermembranespacebecomesnegative

duetotheprotonsbeingpumpedoutofit.

D)Themitochondrialmatrixbecomesnegative

duetotheprotonsbeingpumpedintoit.

11.Allofthefollowingstatementsdescribethenet

resultofoxidativephosphorylationEXCEPT:

A)NADHandFADH2areoxidizedtogenerate

aprotongradient.

B)ControlledprotonflowthroughATP

synthaseisusedtoregenerateATP.

C)Oxygenisthefinalelectronacceptorinthe

electrontransportchain.

D)Theproductsofoxidativephosphorylation

areretainedforthenextroundofcyclic

phosphorylation.


OfficeHours:Lessons3-5Review

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metabolism - blueprint prep · introduction hi, i’m phil! u mcat content writer u tutored and...

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