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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

Hi, I'm Phil!

u MCAT Content writer u Tutored and taught for 9+ years u Attended University of Nebraska Medical Center as an MD/PhD student. ü Next Step is a team of test prep and educational experts committed to excellence.

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• Began in 2009 as a tutoring company • Focus on graduate admissions tests only • Team of educational experts • First company to have materials built from ground up for 2015 MCAT format • Now the first company to have new 2018

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BiochemStudyStrategies

Don'tmisstheforestforthetrees!

• Whydoesthismatterphysiologically?

Whataretheinputs&outputsofa

pathway?•

Biomolecules:howdoeschemical

structureconnecttobiologicalfunction?

Pathways:whatdoesapathwayDO?

Howisapathwayregulated(big-picture?)

BiochemStudyStrategies

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

• Tightlyregulatedtoavoidfutilecyclewithgluconeogenesis

OfficeHours:BiochemContentReview

Glycolysis

• Input:Steps1-5

Output:Steps6-10

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

OfficeHours:BiochemContentReview

Kinases-addsphosophate

Phosphatases=RemoveP!

Phosphorylases-Addsphosphate!

Gluconeogenesis

• Creationofglucosefrompyruvate,lactate,glycerol(lipids),someAAs mitochondriacytosol • Occursmainlyinliver(+cortexofkidneys).

Differentfromglycolysisin3majorsteps

• Ifnot"bypassed"wouldbehighlyendergonic.

Fastingconditionspromotegluconeogenesis

PEPCK

à↑gluconeogenesis

High[AMP]promotesgluconeogenesis.

High[ATP]inhibitsgluconeogenesis.

OfficeHours:BiochemContentReview

Glycolysis&Gluconeogenesis

EXCEPTthat:

A)itoccursinthecytoplasm.

B)itisananaerobicprocess.

C)itresultsinanetproductionof4ATP.

OfficeHours:BiochemContentReview

Glycolysis&Gluconeogenesis

adifferencebetweenglycolysisand gluconeogenesis?

A)Glycolysiscanoccurinallcells,while

gluconeogenesiscannot.

B)Glycolysisandgluconeogenesisoccurin

differentpartsofthecell.

C)OnlygluconeogenesisrequiresATPto

function.

D)Glycolysiscanoccurintheabsenceof

A)ADPB)AMPC)Acetyl-CoAD)Glucose

OfficeHours:BiochemContentReview

KrebsCycle

• IndirectlyproducesmanyATP.

3NADH,1FADH2,1GTP

2:why?

Occursinmitochondria.

Pyruvateàacetyl-CoAoccursviathePDC

• Acetyl-CoAßpyruvate,fattyacids,ketogenicAAs,etc.

Irreversiblesteps:

1.Acetyl-CoA+oxaloacetate+H

2O→citrate+CoA-SH

2C4C6C

5C4C

OfficeHours:BiochemContentReview

KrebsCycle

• Notthermodynamicallyfavorable:whydoesitproceed?•

Regulatedat4majorpoints:

• AtthePDC(upsteamofcycleitself) • Step3:inhibitedbysuccinyl-CoAandNADH[products],ATP • Step4:inhibitedbysuccinyl-CoA,NADH,ATP

Basicprinciple:negativefeedback!

OfficeHours:BiochemContentReview

KrebsCycle

6.DuringtheKrebscycle,isocitrateandNAD+

cometogethertoformalpha-ketoglutarate,

NADHandH

+.Whichofthefollowingdescribe thistypeofchemicalreaction?

A)Dehydration

B)Hydration

C)Decarboxylation

D)Oxidation7.IntheKrebscycle,NAD

+andFADreactwith substratestoformNADHandFADH

2.Over

thesameperiodoftimethatninemoleculesof FADH

2areproduced,howmanyunitsofNADH

willbesynthesized?

A)9molecules

B)18molecules

C)27molecules

D)36molecules

OfficeHours:BiochemContentReview

KrebsCycle

8.Passageofonemoleculeofpyruvatethrough

theKrebscycleyieldshowmanymolecules ofATPwhenfollowedthroughoxidative phosphorylation? A)13 B)15 C)30 A)AMP

B)ADPC)NADHD)NAD

OfficeHours:BiochemContentReview

Electrontransportchain

2pathwaysactually!

- OneforNADH

OneforFADH2

Electrontransportchain

Generalinformation:

• Occursalonginnermitochondrialmembrane lowerreduction potentialhigherreduction potential terminalelectron acceptor • ProvidesenergyforATPsynthase(protongradient) ~30ATPperglucose

Mechanism:

• 4membrane-boundcomplexestransfere-fromNADHand FADH

2andpumpH+intointermembranespace

• [H+]intermembranespace>[H+]matrix • Protonsrushdowngradient,poweringATPsynthase

Regulation:

• Inhibitedby↓O2,↓[ADP]/[ATP],↓NADH

Othermetabolicpathways

Glycogenesis

Glycogenolysis

Betaoxidationoffattyacids

Pentosephosphatepathway

Electrontransportchain

10.Whichofthesestatementsregardingproton

pumpingisaccurate?

A)Theintermembranespacebecomespositive

duetotheprotonsbeingpumpedintoit.

B)Themitochondrialmatrixbecomespositive

duetotheprotonsbeingpumpedoutofit.

C)Theintermembranespacebecomesnegative

duetotheprotonsbeingpumpedoutofit.

D)Themitochondrialmatrixbecomesnegative

A)NADHandFADH

2areoxidizedtogenerate

aprotongradient.

B)ControlledprotonflowthroughATP

synthaseisusedtoregenerateATP.

C)Oxygenisthefinalelectronacceptorinthe

electrontransportchain.

D)Theproductsofoxidativephosphorylation

areretainedforthenextroundofcyclic phosphorylation.

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