MUSCLE METABOLISM

Group Muscle Protein Notes

most important, 65% of weight, thick filaments, 2 identifcal heavy chains (forms superhelix) with a
Myosin (M) globular head at N terminus and 4 light chains (at globular heads), binds other myosin molecules,
binds actin filaments, ATPase activity
Major Actin (A) thin filaments, 20-25% of muscle proteins, 2 strands of polymerized monomers
Tropomyosin (Tm) 2 α helical chains wound along actin groove, blocks myosin binding site in relaxed muscle
three subunits (TnC – Ca binding, TnI – binds actin, TnT – binds tropomyosin), in thin filament,
Troponin (Tn)
regulator of muscle contraction
α-actinin binds to ends of actin filaments, may attach them to Z disk
Desmin & Vimentin at A disk periphery, keep adjacent myofibrils in lateral register
Associated
largest polypeptide known, extends from thick filament to Z disk, acts as spring to keep thick filament
with Z disk Titin
Minor centered in sarcomere, may control length of thick filaments
Nebulin repeating 35-residue acting binding motif, predicted to be α-helical
Associated C & M proteins participate in thick filament assembly
with M disk Dystrophin inner surface of muscle membrane, anchor specific membrane glycoproteins in RBC

Duchenne Muscular Dystrophy (DMD) Becker Muscular Dystrophy (BMD)

2-5 years, degeneration exceeds regeneration, death at 20 y/o, 5-10 years, less progression, longer lifespan,
usually no dystrophin altered or semifunctional dystrophin
Mutation @ C-terminus or actin binding region Mutation @ α helix (shortening)

Organization of Striated Muscle

 Muscle  bundle of muscle fibers  muscle fiber  myofibril  sarcomere
 Sarcomere:
Z disk A Band H band I band M disk
Z  Z = sarcomere Electron dense, thick + thin filaments Thick filaments 2x actin, thin filaments Middle of sarcomere

 Sliding Filament Model – thin slides over thick filaments, A bands remain constant, I bands contract, Z disks approach each other
 Crossbridge cycle
1. ATP binding – ATP binds to myosin, A-M bridge rapidly dissociates
2. ATP hydrolysis – Free myosin moves into position to attach to actin, ATP hydrolyzed but does not release ADP + Pi
3. A-M binding – Myosin rebinds to actin
4. Powerstroke – actin displaces Pi then ADP from myosin, myosin heads bend (stroke), ready to ATP binding
o Each powerstroke of 500 myosin heads = 10 nm contraction
o During strong contraction, powerstroke repeated 5 times / second
o Mn2+ as cofactor
 Sequence: Action potential  Ach release  Depolarization  opening of Ca channels  ↑ ICF Ca  Ca binds to TnC  Tm reveals binding site
 Crossbridge cycle  contraction  Ca returns to SR  TnC releases Ca  Tm covers binding site  relaxation
 Regulation by calcium
o Ca + TnC  Tn drags Tm 10 Å  binding site revealed  myosin binds
 Sarcoplasmic Reticulum – Ca reuptake via:
o calsequestrin – lots of negative AA
o calcium ATPase pump – pumps Ca into SER

Muscle Energy Production

 Principal task – perform mechanical energy at the expense of ATP
 ATP synthesis from glucose, fatty acids, ketone bodies
 During light exercise – glucose  CO2, H2O
 Muscle contraction increases O2 consumption, especially cardiac muscle
 ATP Generation Pathways
Creatine Phosphate Aerobic respiration Anaerobic respiration
Pathway Uses creatine kinase Glucose + O2  ATP + H2O Glycolysis  pyruvate
ATP Quickly exhausted, reversible,
20x more ATP than anaerobic 2.5x faster than aerobic
generation replenished during rest
long term source (>40s), resting/slowly-active Used in moderate period (30-40s) of strenuous
Usage 1st used, short periods (10-15s)
muscle, with FA, glucose / glycogen if very active activity, long term use = ↑ lactic acid

 Energy Metabolism
o Rapid ATP replenishment – creatine phosphate + ADP + creatine kinase  ATP + creatine
o ADP + adenlyate kinase (myokinase)  ATP and AMP
o AMP + AMP deaminase  IMP; to pull equilibrium of reaction in favorable direction
o Glycogen – most important long term reserve

 Degradation – activated by epinephrine via cAMP  activation of phoshorylase kinase  glycogen phosphorylase
 o Oxidative phosphorylation – most efficient pathway, supplies almost all of ATP for cardiac muscle
o For slowly-contracting skeletal muscles – oxygen facilitated by myoglobin

 Metabolism of Proteins and Amino Acids

o Proteins – energy reserve during prolonged starvation, increased with testosterone and anabolics
o Amino acid – increased with cortisol, substrates for citric acid cycle, Ala&Gln  gluconeogenesis in liver

 Cardiac muscle – continuously and spontaneously contracts; depends on aerobic respiration

 Smooth muscle – slow, long lasting, involuntary contractions; spindle shaped, mononucleated, no myofibril formation
o Myosin – max ATPase 10% of striated muscle, A-M binding when one of light chains is phosphorylated @ Ser, thick filaments whose
cross-bridges lack repeating pattern of striated muscle