Muscle Metabolism IUA 2013

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    Musclemetabolism

    Dr.AtifHassanKhirelsied

    DepartmentofBiochemistry

    Facult

    ofMedicine

    InternationalUniversityofAfrica,Khartoum,Sudan

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    Learningobjectives

    Attheendofthissessionthestudentsshouldbeable

    to:

    Listthe

    energy

    sources

    of

    the

    muscles

    IdentifythedifferencesinATPsynthesisamongdifferent

    types

    o

    musc e

    ce s.

    escr e owenergy sut ze ur ngmusc econtraction

    Differentiatethetypesofmuscleonthebasisoftheir.

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    Introduction

    MusclesmustcontinuouslymakeATPtoprovidethe

    ener

    formuscle

    contraction.

    12/24/2012 Atif H.Khirelsied3

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    Introduction

    ATP h drol sis istheimmediatesourceofener for

    musclecontraction.

    TheenergyreleasedfromtheATPhydrolysiswillbeusedto:

    yos n ase

    Ca2+ ATPase intheSRmembrane

    + +

    12/24/2012 Atif H.Khirelsied4

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    MusclecellsregenerateATPbythreeways

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    Thefuelsofmuscle

    muscleactivity:

    .

    Glycogenstorage.

    ucose

    rom

    oo . Triacylglycerol(storedwithinthemuscle).

    Fattyacids(fromadiposetissue).

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    Muscleenergyrequirement

    T e ue suse ymusc e i eraccor ingto:

    Thetype

    of

    muscle

    fiber

    Thetypeofactivity

    Theconditionoftheactivit .

    , ,

    accordingtotheparticularevent,fromthe100m

    .

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    Factorsdeterminingfuelutilizationbymuscles

    selected:

    Theamountoffuelstored

    e

    ranspor

    o

    ue

    o

    e

    musc e Theavailabilityofoxygenforthemuscle

    Theintensityoftheexercise

    The

    duration

    of

    the

    exercise.

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    TypesofSkeletalMuscleFibers

    1. Fastfibers(whitemuscle)

    2. Slowfibers

    (red

    muscle)

    3. Intermediatefibers

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    1. Fasttwitch.

    . , .

    3. Highglycogencontent.

    4. Fewerblood

    vessels

    and

    low

    myoglobin.

    .

    glycolysis.

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    1. Slowtwitch.

    . , .

    3. Dependonaerobicmetabolism.

    4. Utilizefats

    as

    well

    as

    glucose.

    . ave eg ycogens orage.

    6. Manyblood

    vessels

    and

    high

    myoglobin.

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    Comparisonofslowandfasttwitchmusclefibers

    Musclefiber TypeI TypeIIa TypeIIb

    Use(example) Posture Walking Sprinting

    +

    ATPase Activity Low High High

    Fatigueresistance High Intermediate Low

    Capillarydensity High Intermediate Low

    Glycolytic enzymes Low Intermediate High

    oc on r a con en s g n erm ea e ow

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    Themetabolicpathwaysinwhiteandredmusclefibers

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    Thetypeoffiberandfuelusagebymuscles

    Allfibert escanuse hos hocreatine articularl t e

    IIB.

    TypeIIBfiberswhichalsoconvertglycogen tolacticacid

    IntypeIandIIAfibers,mostoftheglycogeniscompletely

    .

    T e ateo t eg ycogenwi epen ont eintensityo t e

    exerciseandthesupplyofoxygen

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    Thetypeoffiberandfuelusagebymuscles

    Glucose canbeoxidizedanaerobicall tolacticacidto

    generateATP.

    Thecapacityofglucoseutilizationislimitedbytheactivity

    (tenfold)andsufficienttoprovidealltheATPrequiredto

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    Theamountoffuelstoredandfuelusageby

    Fuels are stored within the muscle liver and adi ose

    tissueandtheiramountsvaryaccordingto:

    thepreviousphysicalactivity.

    Triacylglycerol,storedwithinthemusclecanbeusedbut

    themostfatfuelisderivedfrominadiposetissue.

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    Theapproximateamountsofvariousfuelsandenergy

    contentinmuscle,liver andadi osetissuein75k male

    containing20

    kg

    muscles

    Fuel Tissue

    Approx.

    Energy(KJ)

    con en g

    Phosphocreatine Muscle Verylittle 15

    Glycogen Muscle

    500

    8000

    Triacylglycerol Muscles Varies 17500

    pose

    tissues

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    Thefueltransportandfuelusagebymuscles

    Bloodbornefuelsare:

    glucose,whichisderivedfromliverglycogen,

    fattyacids

    derived

    from

    adipose

    tissue.

    Fueluptakedependson:

    t e owo oo t roug t emusc e,

    theconcentrationofthefuelintheblood

    .

    muscleandtherateofutilizationofthefuelcanincreaseupto50fold,yettheconcentrationofthefuelsinbloodrema nsremar a ycons an .

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    TheOxygensupplyandfuelusagebymuscles

    Aerobic l col sis roduces about tenfold reater ATP

    thananaerobic glycogenolysis.

    Oxygenisthemajorfactorlimitingperformancein

    .

    Italsolimitsphysicalactivityinmanynonathletesandin

    patients(notableinanemicpatients).

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    Oxygensupplyandfuelusagebymuscles

    Ox ensu l tothemusclesde endsonthefollowin

    factors:

    Theflow

    of

    blood

    throu h

    the

    muscle.

    sizeof

    the

    capillary

    bed.

    Theconcentration(partialpressure)ofoxygenintheblood

    .

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    Oxygensupplyandfuelusagebymuscles

    factors:

    Theuptakeofoxygenfromtheairinthealveoli(canbe

    ,

    diseasee.g.

    emphysema).

    Theconcentrationof2,3bisphosphoglycerateinthe

    .

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    Oxygensupplyandfuelusagebymuscles

    by:

    .

    supplythe

    muscle.

    Decreasingtheflowthroughabdominalandpelvicviscera

    .

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    Numberoferythrocytesandfuelusagebymuscles

    demonstratedby:

    Thebeneficialeffectofblooddopingonathletic

    orduringanemia.

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    Aerobiccapacityandfuelusagebymuscles

    Conditionsdurin whichmostATPis eneratedfrom

    phosphocreatine andglycogeninclude:

    Veryunfitindividuals,duringanyformofphysical

    , ,

    runningupstairs).

    Inelderlypeople(ageingdecreasesmitochondriaand

    x v y .

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    Durationofexerciseandfuelusagebymuscles

    Astheduration oflowintensityexerciseincreases,the

    glucoseandfattyacidsincreases.

    Forprolongedactivitiesfattyacidsbecometheonlyfuel

    available.

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    Estimatesofpercentagecontributionofglucose,glycogenandfatty

    acidstoATP enerationoverfourhoursof h sicalactivit

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    Thechangeinmusclefuelutilizationwiththedurationof100

    e

    75nupt

    a

    Gl co en

    Fattyacid

    ofoxyg

    50

    centage

    25

    l

    asper

    Bloodglucose

    0

    Fu

    100 200 300

    Durationofexerciseinminutes

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    afterbeginning

    of

    physical

    activity

    h f d f l b

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    Theintensityofexerciseandfuelusageby

    Asintensity increases,theutilizationofbloodglucose

    .

    musc eper ormancea ove o max mumpower

    output,therateofglycogenincreasesexponentially.

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    Thesprints

    Onlytwofuelsareusedduringthe100msprint glycogen

    .

    Theglycogenisconvertedexclusivelytolacticacid.

    Asthedistanceextendsto400m,aerobicoxidationof

    glycogenoccurs,producingabout25%oftheATP.

    presentinthemuscle.

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    Fuelutilizationduringsprint

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    Themiddledistances

    As

    the

    distance

    and

    time

    taken

    for

    the

    event

    extends,

    aerobicoxidationbecomesincreasinglyimportantinthe

    generationofATP.

    Thisis

    demonstrated

    by

    the

    decline

    in

    the

    rate

    of

    , .

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    Themarathon

    A

    full

    marathon

    (42.2

    km),

    requires

    the

    oxidation

    of

    about700gofglycogen.

    owever,s nceon ya ou gcan es ore n ver

    plusmuscle,

    another

    fuel

    must

    contribute.

    Thisisfattyacid,derivedfromtriacylglycerol inadipose

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    Indicationsof

    the

    oxygen

    supply

    to

    muscle,

    and

    the

    pathways

    for

    ATP

    generationindifferentathleticevents