biochemistry of muscle

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    Faculty of Dentistry, Hang Tuah University

    2013

    ian Mulawarmanti

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    Body movement (Locomotion) Maintenance of posture Respiration

    Diaphragm and intercostal contractions Communication (Verbal and Facial) Constriction of organs and vessels

    Peristalsis of intestinal tract

    Vasoconstriction of b.v. and other structures (pupils)

    Heart beat Production of body heat (Thermogenesis)

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    1.. Smooth Muscle 2. SKELETAL Muscle 3. Cardiac Muscle

    walls of most viscera, usually attached to bones wall of heartblood vessels, skin under conscious control not under conscious

    controlnot under conscious striated control striatednot striated

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    structure control nuclei Location

    skeletal striated Primarilyvoluntary

    Multiplephripheral

    Attachedto bone

    cardiac striated Involuntary

    Nervus &

    endocrine

    1 rarely2 Centrally

    located

    Heart wall

    smooth Non

    striated

    Involuntary

    Nervus &

    endocrine

    Centrally

    located

    Walls of

    hollow

    organ

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    Other protein

    components ofmuscle fibrils

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    sarcolemmasacroplasmsarcoplasmicreticulum

    transverse tubuletriad

    cisternae of sarcoplasmicreticulumtransverse tubule

    myofibrilactinfilamentsmyosinfilamentssarcomere

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    As a monomer, termed G-Actin, at low ionicstrength and can bind one ATP

    At physiological ionic strength (plus Mg2+), the G-actin forms fibrous polymers termed F-actin. ATPhydrolysis occurs during this process and ADPremains bound to each F-actin subunit

    F-actin is the core of the thin filament, and eachmonomer is capable of binding one myosinglobular head. The coil repeats at roughly everyseventh actin unit.

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    Thick Filamentscomposed of myosincross-bridges

    Thin Filamentscomposed of actinassociated withtroponinand

    tropomyosin

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    also known as myoneuraljunctionsite where an axonandmuscle fiber meet

    motor neuronmotor end platesynapse

    synaptic cleftsynaptic vesiclesneurotransmitters

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    When sarcomeresshorten, thick and thin

    filaments slide past oneanother

    H zones and I bandsnarrowZ lines move closertogether

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    muscle impulses causesarcoplasmic reticulum torelease calcium ions intocytosol

    calcium binds totroponin to change itsshapeposition of tropomyosin

    is alteredbinding sites on actinare exposedactin and myosinmolecules bind

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    myosin cross-bridge attachesto actin binding site

    myosin cross-bridge pullsthin filament

    ADP and phosphatereleased from myosin

    new ATP binds tomyosin

    linkage between actinand myosin cross-bridgebreak

    ATP splits

    myosin cross-bridge goes back

    to original position

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    acetylcholinesteraserapidly decomposes Ach remaining in the

    synapse

    muscle impulse stops

    stimulus to sarcolemma and muscle fiber membrane ceases

    calcium moves back into sarcoplasmic reticulum

    myosin and actin binding prevented

    muscle fiber relaxes

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    The contractile process

    The pumpingof calcium back into thesarcoplasmic reticulumduring relaxation

    Maintaining the sodium/potassium iongradients across the sarcolema(membranepotential)

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    Phosphocreatine

    Glycolysis from Glycogen or Glucose Tricarboxylic acid cycle (TCA or Krebs

    cycle)

    Electron transport chain

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    It is also known as creatine phosphate orPcr, that is an important energy stored in

    the skeletal muscle. Creatineis synthesized in the liver (from

    Arg, Gly, Met), and transported to themuscle cells, where it is phosphorylated bycreatine kinase (ATP is required) to creatinephosphate.

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    ADP+

    Phosphocreatine

    Creatine Kinase

    ATP+

    Creatine

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    This reaction occurs in the sarcoplasm.ATP broken down during contraction is

    rapidly restored.Phosphocreatine is subject to

    depletion during extended periods ofcontraction (intense effort).

    Rephosphorylation of creatine occursat the mitochondrial membrane.

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    It is the sequence of reactions that converts

    glucose pyruvate

    with the concomitant production of a

    relatively small amount of ATP

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    Glycogen is a polysaccharide of glucose(Glc) which functions as the primary short

    term energy storage in muscle cells(myofiber).

    Glycogen is found in the form of granules inthe sarcoplasm, and plays an importantrole in the glucose cycle.

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    Glycogen

    GlycogenPhosphorylase

    Glucose 1-Phosphate

    Glucose 6-phosphate

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    Summary

    1 Glucose + 2ADP + 2Pi +2NAD

    2 Pyruvate + 2ATP + 2NADH +2H + 2H2O

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    It is also known as Citric Acid Cycle

    Krebs cycle.

    It is a series of enzyme-catalyzed chemicalreactions of central importance in all livingcells that use oxygen as part of cellularrespiration.

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    TCA cycle

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    SummaryPyruvate

    1ATP + 4NADH +1FADH + 3CO2

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    It is a chemical reaction between anelectron donor (such as NADH) and an

    electron acceptor (such as O2) to thetransfer of H+ions across a membrane

    These H+ions are used to produceATP, asthey move back across the membrane.

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    Summary NADH

    NAD + 3ATP + 4H2O

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    Process Direct product FinalATP

    GLYCOLYSIS 2 NADH

    2ATP

    4 or 6

    2

    Pyruvate oxidation(two per glucose)

    2 NADH(mitochondrial matrix)

    6

    Acetyl-CoA oxidation 6 NADH(mitochondrial matrix)

    2 FADH22 ATP

    184

    2

    Total yield per molecule of glucose

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    Release of Ca2+

    through voltage-or Ca2+-sensitivechannel activatescontraction

    Pumps inducerelaxation

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    Ca2+Channels and Pumps

    Release of Ca2+from the SR triggers

    contraction Reuptake of Ca2+into SR relaxes muscle So how is calcium released in response to

    nerve impulses? Answer has come from studies of antagonistmolecules that block Ca2+channel activity

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    At rest tropomyosin blocks

    the myosin binding sites on

    actin.

    When calciumbinds to thetroponin complex aconformational change

    results in the movement of

    the tropomyosintropinincomplex and exposure of

    actinsmyosin binding sites.

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    Follow the actionpotential

    When an actionpotential meets themuscle cells

    sarcoplasmic

    reticulum (SR)stored Ca2+ is

    released.

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    An individual muscle cell either contractscompletely or not all.

    Individual muscles, composed of manyindividual muscle fibers, can contract tovarying degrees.

    One way variation is accomplished by varying

    the frequency of action potentials reach themuscle from a single motor neuron.

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    Graded musclecontraction can also

    be controlled by

    regulating thenumber ofmotor units involved

    in the contraction

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    Recruitment of motor neurons increasesthe number of muscle cells involved in acontraction

    Some muscles, such as those involved inposture, are always at least partially

    contracted

    Fatigue is avoided by rotating among motorunits

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    In addition to skeletal muscle, vertebrateshave cardiac and smooth muscle

    Cardiac muscle: similar to skeletal muscle Intercalated discs facilitate the coordinated

    contraction of cardiac muscle cells. Can generate there own action potentials. Action potentials of long duration.

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    Smooth muscle: lacks the striations seen in bothskeletal and cardiac muscle

    Contracts with less tension, but over a greaterrange of lengths, than skeletal muscle. No T tubules and no SR Ca2+ enters the cytosol from via the plasma

    membrane. Slow contractions, with more control over

    contraction strength than with skeletal muscle. Found lining the walls of hollow organs

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    12/02/2008 Biochemistry: MusclesPage 50

    of 46

    No troponin complex in smooth muscle

    Ca2+activates myosin light chain kinase(MLCK) which phosphorylates LC2, theregulatory light chain of myosin

    Ca2+

    effect is via calmodulin - a cousin ofTroponin C

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    Hormones regulate contraction -epinephrine, a smooth muscle relaxer,

    activates adenylyl cyclase, making cAMP,which activates protein kinase, whichphosphorylates MLCK, inactivating MLCKand relaxing muscle

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    creatine phosphate stores energy that quickly converts

    ADP to ATP

    1) Creatine phosphate 2) Cellular respiration

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    Anaerobic Phaseglycolysisoccurs in cytoplasmproduces little ATP

    Aerobic Phasecitric acid cycleelectron transport chainoccurs in themitochondriaproduces most ATPmyoglobinstores extraoxygen

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    Muscle tissue has two sources of oxygen. diffuses in from the blood

    released by myoglobin inside muscle fibers

    Aerobic system requires O2 to produce ATPneeded for prolonged activity increased breathing effort during exercise

    Recovery oxygen uptake elevated oxygen use after exercise (oxygen debt)

    lactic acid is converted back to pyruvic acid

    elevated body temperature means all reactions

    faster

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    oxygen not availableglycolysis continuespyruvic acid convertedto lactic acid

    liver converts lacticacid to glucose

    Oxygen debtamount of oxygen needed by liver cells to use the accumulatedlactic acid to produce glucose

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    by-product of cellular respiration

    muscle cells are major source of body heat

    blood transports heat throughout body

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    Slow oxidative (slow-twitch)

    red in color (lots of mitochondria, myoglobin & blood vessels)

    prolonged, sustained contractions for maintaining posture Fast oxidative-glycolytic (fast-twitch A)

    red in color (lots of mitochondria, myoglobin & blood vessels)

    split ATP at very fast rate; used for walking and sprinting

    Fast glycolytic (fast-twitch B) white in color (few mitochondria & Blood Vessel, low myoglobin)

    anaerobic movements for short duration; used for weight-lifting

    (angkat berat)

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    These differences are due primarily to themale sex hormone testosterone

    With more muscle mass, men are generallystronger than women

    Body strength per unit muscle mass,however, is the same in both sexes

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    With age, connective tissue increases and musclefibers decrease

    Muscles become stringier and more sinewy By age 80, 50% of muscle mass is lost (sarcopenia) Decreased density of capillaries in muscle Reduced stamina Increased recovery time Regular exercise reverses sarcopenia

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    Inability to contractdepletion of creatine phosphate

    decline of Ca+2 within the sarcoplasm

    Commonly caused fromdecreased blood flowinsufficient oxygen or glycogen

    Ion imbalances across the sarcolemma

    Accumulation of lactic acidinsufficient release of acetylcholine from motor neurons

    Cramp sustained, involuntary muscle contraction

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