Biochemistry of Muscle
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Transcript of 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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