Muscle Metabolism

Graphicsareusedwithpermissionof: PearsonEducationInc.,publishingasBenjaminCummings(http://www.awbc.com)

Page 1. Introduction Skeletal muscle must continuously make ATP to provide the energy for muscle contraction. Page 2. Goals TounderstandthecellularprocessesforsynthesisofATP. Tocompareandcontrastaerobicandanaerobicprocessesinthemusclecell. ToexaminethedifferencesinATPsynthesisamongdifferenttypesofmusclecells. Page 3. Role of ATP ImportantrolesofATPinmusclecontraction: 1.ATPbindstomyosinheadsanduponhydrolysisintoADPandPi,transfersits energytothecrossbridge,energizingit. 2.ATPisresponsiblefordisconnectingthemyosincrossbridgeattheconclusion ofapowerstroke. 3.ATPprovidestheenergyforthecalciumionpumpwhichactivelytransports calciumionsbackintothesarcoplasmicreticulum. Page 4. Structure of Adenosine Triphosphate (ATP) StructureofATP:

Note:ATPhasthreephosphategroups.Thestructureofaphosphategroup(Pi)is:

The bond between the last two phosphate groups is high energy and therefore blinkingyellow. Page 5. Hydrolysis of ATP ThisanimationshowsthehydrolysisofATP. SummaryofthehydrolysisofATP: ATP + H2O ADP + Pi + energy

ThehydrolyticenzymebindstheATPandcatalyzesthereaction.Twoexamplesof hydrolyticenzymeswithinthemuscleare: ThemyosinheadfunctionsasahydrolyticenzymewhenithydrolyzesATP intoADPandPi.Theenergyreleasedisusedtopropthemyosincrossbridge upintoitshighenergyposition. Thecalciumionpumpwhichactivelytransportscalciumionsbackintothe sarcoplasmic reticulum will act as a hydrolytic enzyme when it hydrolyzes ATPintoADPandPi.Theenergyreleasedisusedtochangetheshapeofthe pumpallowingthecalciumionstogobackintotheSR. During the reaction, the water (shown in blue) breaks the high energy bond betweenthelasttwophosphategroups.ThewatersplitsapartandtheOHfrom thewaterendsupontheinorganicphosphate(sometimesabbreviatedPi)andthe otherHfromthewatergoesontothephosphategroupwhichremainsattachedto theADP. ADPiscalledadenosinediphosphatebecauseonlytwophosphategroupsremainon it. TheenergycontainedinthebondbetweenthelasttwophosphatesonATPhasbeen releasedandisshownhereasaglowing"E". Thereisstilloneadditionalhigh energybondleftintheADP.(Thathighenergybondwillnotbeimportantinthis module.) TheenergyreleasedfromtheATPhydrolysiswillbeusedto Disconnect the myosin cross bridge from the binding site on actin at the conclusionofapowerstroke. Energizethepowerstrokeofthemyosincrossbridge. Energizethecalciumionpumpwhichactivelytransportscalciumionsbackinto thesarcoplasmicreticulum. Page 6. Dehydration Synthesis of ATP ThisanimationshowsthedehydrationsynthesisofATP. Itiscalled"dehydration synthesis" because water is removed (dehydration) and a bigger molecule is synthesized from two smaller ones. Some textbooks call this process "condensation"becauseawatermoleculeisreleased. SummaryofthedehydrationsynthesisofATP: ADP + Pi + energy ATP + H2O The synthetic enzyme binds the ADP and catalyzes the reaction. During the reaction,water(shownattachedtotheADPandphosphategroupsinblue)splits offandtheinorganicphosphate(Pi)attachestotheADPtoformATP. Thisprocessrequiresenergysinceahighenergybondisformed. Theenergyis shownhereasaglowingyellowballwhichappears.Oneofthemainfunctionsof thissectionistoexaminewherethatenergycomesfrom. Page 7. ATP as "Energy Currency" dehydration synthesis ATP hydrolysis moving myofilaments & transporting ions

ATP
"energy currency"

Page 8. Overview of "Energy Currency" MusclecellssynthesizeATPthesethreeways: 1.Hydrolysisofcreatinephosphate 2.Glycolysis 3.TheKrebscycle&oxidativephosphorylation Page 9. Creatine Phosphate The immediate source of energy for rebuilding ATP is the high energy molecule creatinephosphate.Thephosphateincreatinephosphate,canbetransferredto ADPtoformATPinaprocesscalledsubstratephosphorylation. However,there isn'tmuchcreatinephosphatestoredinmusclecells.

Page 10. Sources of Glucose Twosourcesofglucosetomuscles: 1.Bloodglucose. 2.Breakdownofglycogenintoglucosewithinthemusclecell. Page 11. Glycolysis Summaryoftheprocessofglycolysis: Glucose glycolysis 2 Pyruvic + Acid 2 ATP

Page 12. Anaerobic Pathway: Lactic Acid Fillintheemptyboxestoshowglycolysisandtheanaerobicpathway:

Page 13. Sources of Oxygen Theoxygenneededforaerobicmetabolismisavailabletomusclecellseitherdirectly fromthebloodoritcanbestoredinanoxygenbindingproteincalledmyoglobin. Page 14. Aerobic Pathway Fillintheemptyboxestoshowtheaerobicpathway:

Page 15. Summary of ATP Production ThisanimationsummarizesthethreeprocessesforproducingATP: Creatinephosphatepathway Glycolysis/anaerobicpathway Aerobicpathway ItalsoremindsusthatATPisneededbythemusclecellforthepowerstrokeofthe myosincrossbridge,fordisconnectingthecrossbridgefromthebindingsiteon actin,andfortransportingcalciumionsbackintotheSR. Page 16. Creatine Phosphate "Factory" Thisanimationdramaticallyillustratesthisprocess:

Page 17. Glycolysis "Factory" Thisanimationdramaticallyillustratestheprocessofglycolysisfromglycogen: Glycogen Glucose glycolysis 2 Pyruvic + 2 ATP Acid

Page 18. Anaerobic Pathway "Factory"

Thisanimationdramaticallyillustrateslacticacidformation: Glycogen Glucose glycolysis 2 Pyruvic + 2 ATP Acid Lactic Acid Noticehowsomeofthelacticacidstaysinthemuscle,andsomegoesbackout intotheblood.Thelacticacidthatstaysinthemuscle,decreasesthepHofthe muscleandcontributestothemusclefatigue. Page 19. Conversion to Acetyl CoA Thisanimationshowspyruvicacidenteringthemitochondriainthepresenceof oxygenanditsconversiontoacetylCoA: Pyruvic Acid Acetyl Co A Page 20. Aerobic Respiration "Factory" Thisanimationillustratesaerobicrespiration.Pyruvicacidentersthemitochondria andisconvertedtoacetylCoA. TheAcetylCoAenterstheKrebscycleand36 ATPs per glucose are produced during oxidative phosphorylation. The by productsarecarbondioxideandwater: Carbon Dioxide Water 36 ATP Page 21. Review of ATP "Factory" Thispageallowstheyoutogobackandreview. Page 22. Comparison of ATP Production ThisanimationcomparesATPproductionviathethreedifferentpathways: Hydrolysisofcreatinephosphate:1ATPpercreatinephosphatemolecule Glycolysis:2ATPperglucose Krebscycle&oxidativephosphorylation:36ATPperglucosemolecule Creatine phosphate and anaerobic metabolism can provide short bursts of ATP quickly but only with aerobic respiration (Krebs cycle and oxidative phosphorylation)willenoughATPbeproducedtoprovidesustained,longduration muscleactivity. **Nowisagoodtimetogotoquizquestion14:
ClicktheQuizbuttonontheleftsideofthescreen. Workthroughquestions14. Afteransweringquestion4,clicktheBacktoTopicbuttonontheleftsideofthescreen. Togetbacktowhereyouleftoff,clickonthescrollingpagelistatthetopofthescreenandchoose"23. Recovery&Resting".

Pyruvic Acid

Acetyl Co A

Page 23. Recovery and Resting

Aftertheexerciseperiodisconcluded,themuscleneedstorestoresthecreatine phosphate,glycogen,andoxygenlevels.Italsoneedstouseupexcesslacticacid which may have accumulated during exercise. This is sometimes called the "oxygendebt". Fillintheblanksinthisdiagramasyouviewtheanimationonpayingbackthe "oxygendebt": Convertinglacticacidbackintopyruvicacid,whichcannowaerobicallyproduce ATP(1). TheATPrephosphorylatescreatineintocreatinephosphate(2). Glucoseentersthecellfromthebloodandformsglycogen(3). Oxygenentersthecellfromthebloodandreattachestomyoglobin(4).

Page 24. Metabolic Variations of Muscle Fiber Types Therearetwotypesofmusclecellswithinagivenmuscle,whitemusclefibersand redmusclefibers,whichdifferinsize,colorationandmetabolism. Page 25. Features of White Muscle Fibers Characteristicsofwhitemusclefibers: Largeindiameter Lightincolorduetoreducedorabsentmyoglobin Surroundedbyonlyafewcapillaries Haverelativelyfewmitochondria Haveahighglycogencontent

SynthesizeATPmainlybyglycolysis Page 26. Metabolism in White Muscle Fibers Metaboliccharacteristicsofwhitemusclefibers: Useglycolysis,whichsynthesizesATPquickly,resultinginfastcontractions. Allowforpowercontractionsduetolargenumbersofmyofilamentsbecausethey havealargediameter. Theyfatiguerapidlyduetobuildupoflacticacidanddepletionofglycogen. Theyarewellsuitedforactivitiesrequiringpowerandspeedforashortduration. Whitemusclefibersarealsocalled"fasttwitchglycolyticfibers." Page 27. Features of Red Muscle Fibers Characteristicsofredmusclefibers: Halfthediameterofwhitemusclefibers Darkredincolorduetoalargequantityofmyoglobin Surroundedbymanycapillaries Havemanymitochondria Havealowglycogencontent SynthesizeATPmainlybytheKrebscycleandoxidativephosphorylation Page 28. Metabolism in Red Muscle Fibers Metaboliccharacteristicsofredmusclefibers: UseKrebscycleandoxidativephosphorylation,whichsynthesizesATPrelatively slowlycomparedtoglycolysis,resultinginprolongedcontractions. Theyarefatigueresistant. They are well suited for activities requiring endurance and continuous contraction. Redmusclefibersarealsocalled"slowtwitchoxidativefibers". Page 29. Comparison of Muscles Individualsthatengageinfast,intense,sporadicactivities,suchassprinting,tend tohavemorewhite,fasttwitch,fatiguepronefibers. Individualstheengagein slower,longermuscularactivities,suchasjogging,havemorered,slowtwitch, fatigueresistantfibers. Page 30. Summary ATPmustbesynthesizedinmusclecellstoreplaceATPusedformuscle contraction. ATPissynthesizedbyhydrolysisofcreatinephosphate,glycolysis,andtheKrebs cycleandoxidativephosphorylation. WhitemusclefibersmainlyuseglycolysisforsynthesizingATP;thesefibersare quickandpowerful,butfatiguerapidly. RedmusclefibersmainlyusetheKrebscycleandoxidativephosphorylationfor synthesizingATP;thesefibersarefatigueresistantandhaveahighendurance. **Nowisagoodtimetogotoquizquestions5and6:
ClicktheQuizbuttonontheleftsideofthescreen. Clickonthescrollingpagelistatthetopofthescreenandchoose"5.MuscleMetabolismMania". Workthroughquizquestions56.

Notes on Quiz Questions:

Quiz Question #1: Sequence of Metabolic Pathway This question allows you to predict the sequence of steps in the aerobic synthesisofATP,startingwithglycogen. Lacticacidisnotusedsincethisisanaerobicpathway. Quiz Question #2: Anaerobic Process Thisquestionsasksyoutopredictwhatpartofthesequenceinquestion1is anaerobic. Quiz Question #3: Aerobic Process Thisquestionsasksyoutopredictwhatpartofthesequenceinquestion1is aerobic. Quiz Question #4: Storehouse of Glucose Thisquestionasksyoutopredictwhatpartofthesequenceinquestion1stores glucoseinmusclecells. Quiz Question #5: Muscle Metabolism Mania Thisquestionallowsyoutochosetheenergysources,oxygenrequirements,ATP production, end products, and muscle fiber types for each of the three importantmetabolicpathwaysinmusclecells. Pleasenote,theremaybeatypographicalerrorinthreeoftheanswerboxesif you are playing alone. Under energy source for hydrolysis of creatine phosphate, glycolysis, and Krebs cycle and oxidative phosphorylation, the answerschoicesshouldread:Glucose,creatinephosphate,oxygen,andacetyl CoA,unlessyougeta"MetabolicMultiplier",inwhichcasetheanswerchoices willbefine. Quiz Question #6. White and Red Muscle Fiber Puzzles Inthisquestionyoudecidewhichpointsarecharacteristicsofwhitemuscleand whicharecharacteristicofredmuscle.

Study Questions on Muscle Metabolism:

1.(Page1.)WhyisitnecessaryformuscletohavemechanismstomakeATPquickly? 2. (Page 3.) Which of these is not an important role of ATP in skeletal muscle contraction? a. Disconnecting the myosin cross bridge from the binding site on actin at the conclusionofapowerstroke. b.Exposureofthemyosinbindingsitesonactin. c.Energizingthepowerstrokeofthemyosincrossbridge. d.Energizingthecalciumionpumpwhichactivelytransportscalciumionsbackinto thesarcoplasmicreticulum.

3.(Page4.)WhichoftheseisnotapartoftheATPmolecule? a.adeninenucleotide b.phosphategroups c.ammonia d.highenergyphosphatebonds 4.(Page5.)FillintheblanksinthefollowingequationforthehydrolysisofATP. ATP + ______ ______+______+_______

5.(Page5.)WhyisthereactionthatreleasesenergyfromATPtermeda "hydrolysis" reaction? 6.(Page5.)GiveaspecificexampleofahydrolyticenzymethathydrolyzesATPintoADP andPiinmusclecells. 7.(Page6.)Fillintheblanksinthefollowingequationforthedehydrationsynthesisof ATP. _____ +______ +______ ______ + ATP

8.(Page6.)WhyistheproductionofATPfromADPtermeda"dehydrationsynthesis" reaction? 9.(Page7.)WhyisATPoftencalled"energycurrency"? 10.(Page7.)MusclecellshaveonlyenoughATPtolastfor____________duringanactive contractionperiod. 11.(Page8.)ListthreeprocessesthatmusclecellsusetomakeATPwhenitisneeded formusclecontraction. 12.(Page9.)WhatisthemostimmediatesourceofenergyforrebuildingATPwithin musclecells? 13.(Page9.)FillinthefollowingblankstoshowtheproductionofATPfromCreatine phosphate: ______________+______________ ______________+______________

14.(Page10.)Whatarethetwosourcesofglucosetomusclecells? 15.(Page11.)Whataretheendproductsofglycolysis? 16.(Page12.)Whathappenstopyruvicacidintheabsenceofoxygen? 17.(Page12.)Whathappensifamuscleisdeprivedofoxygenfortoolongwhenitis physicallyactive?

18.(Page13.)Whatisthenameoftheoxygenbindingproteinwithinmuscle? 19. (Page 14.) Where, within a muscle cell, will the Krebs cycle and oxidative phosphorylationoccur? 20.(Page14.)Whataretheendproductsoftheaerobicpathway? 21.(Page14.) Thetotalenergyharvestfromglycolysis,theKrebscycleandoxidative phosphorylationis38ATPmoleculesforeachglucosemoleculemetabolized. a.HowmuchofthatATPisgeneratedduringglycolysis? b. How much of that ATP is generated during the Krebs cycle and oxidative phosphorylation? 22.(Page22.)Duringwhichoftheseactivitieswouldcreatinephosphateandanaerobic metabolism be more important. During which of these activities would aerobic respiration(Krebscycleandoxidativephosphorylation)bemoreimportant.Why? a.veryfastsprintingforashortdistance b.slowjoggingforalongdistance 23.(Page23.)Aftertheexerciseperiodisconcluded,whatreserveshavebeendepleted within the muscle cells? In addition, what byproduct tends to buildup in the musclecell? 24. (Page 23.) To restore the ______________ after exercise, muscle cells convert ________________,presentinthecytosol,backintopyruvicacid,whichentersthe Krebscycle,producing______________,whichisusedtorephosphorylatecreatine into creatine phosphate. Glycogen is also synthesized from ______________ and additionaloxygenrebindsto________________. 25.(Page24.)Whatarethenamesofthetwodifferenttypesofmusclecells? 26.(Page25.)Listseveralstructuralfeaturesthatwhitemusclecellshavethatexplains whythesemusclefibersmainlyuseglycolysistosynthesizeATP(asopposedtothe Krebscycleandoxidativephosphorylation). 27.(Page26.)Whyarewhitemusclefibersalsocalled"fasttwitchglycolyticfibers?" 28.(Page27.)Listseveralstructuralfeaturesthatredmusclecellshavethatexplains whythesemusclefibersmainlyuseKrebscycleandoxidativephosphorylationto synthesizeATP(asopposedtoanaerobicmetabolism). 29.(Page28.)Whyareredmusclefibersalsocalled"slowtwitchoxidativefibers?"