Biochemistry of Muscle
Biochemistry of Muscle
2. SKELETAL Muscle
3. Cardiac Muscle
structure
skeletal striated
control
Primarily voluntary
nuclei
Location
cardiac
striated
Involuntary
Nervus & endocrine
smooth
Non striated
Myofibrils are built of 3 kinds of protein contractile proteins myosin and actin regulatory proteins which turn contraction on & off troponin and tropomyosin structural proteins which provide proper alignment, elasticity and extensibility titin, myomesin, nebulin and dystrophin
5
sarcolemma sacroplasm sarcoplasmic reticulum transverse tubule triad cisternae of sarcoplasmic reticulum transverse tubule myofibril actin filaments myosin filaments sarcomere
Thin filaments consist of two strands of actin and one tropomyosin coiled about each other
Thick filaments consist of myosin molecules.
Composed of 6 highly conserved polypeptide chains Two 220 kDa heavy chains that have elongated globlular heads, and long fibrous helical tails. Each head region contains an ATP-binding site/ATPase function Two pairs of light chains, termed essential light chains and regulatory light chains.These interact with the globular heads of the heavy chains, and regulate ATPase functions depending on their phosphorylation status.
As a monomer, termed G-Actin, at low ionic strength and can bind one ATP At physiological ionic strength (plus Mg2+), the Gactin forms fibrous polymers termed F-actin. ATP hydrolysis occurs during this process and ADP remains bound to each F-actin subunit
F-actin is the core of the thin filament, and each monomer is capable of binding one myosin globular head. The coil repeats at roughly every seventh actin unit.
13
Tropomyosin: a two chain fibrous protein that attach to F-actin in the groove between its filaments Troponins: three protein components, troponin C, a calcium binding protein like calmodulin; troponin I, which blocks the myosin binding site on F-actin; troponin T which binds to tropomyosin and the other troponins
also known as myoneural junction site where an axon and muscle fiber meet motor neuron motor end plate synapse synaptic cleft synaptic vesicles neurotransmitters
17
When sarcomeres
shorten, thick and thin filaments slide past one another H zones and I bands narrow Z lines move closer together
18
muscle impulses cause sarcoplasmic reticulum to release calcium ions into cytosol calcium binds to troponin to change its shape position of tropomyosin is altered binding sites on actin are exposed actin and myosin molecules bind
19
myosin cross-bridge attaches to actin binding site myosin cross-bridge pulls thin filament ADP and phosphate released from myosin new ATP binds to myosin linkage between actin and myosin cross-bridge break ATP splits myosin cross-bridge goes back to original position
20
21
Phosphocreatine Glycolysis from Glycogen or Glucose Tricarboxylic acid cycle (TCA or Krebs cycle) Electron transport chain
It is also known as creatine phosphate or Pcr, that is an important energy stored in the skeletal muscle. Creatine is synthesized in the liver (from Arg, Gly, Met), and transported to the muscle cells, where it is phosphorylated by creatine kinase (ATP is required) to creatine phosphate.
ADP + Phosphocreatine
Creatine Kinase ATP + Creatine
This reaction occurs in the sarcoplasm. ATP broken down during contraction is rapidly restored. Phosphocreatine is subject to depletion during extended periods of contraction (intense effort). Rephosphorylation of creatine occurs at the mitochondrial membrane.
glucose pyruvate
with the concomitant production of a relatively small amount of ATP
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 in the sarcoplasm, and plays an important role in the glucose cycle.
Glycogen
Glycogen Phosphorylase Glucose 1-Phosphate Glucose 6-phosphate
Summary
It is also known as Citric Acid Cycle Krebs cycle. It is a series of enzyme-catalyzed chemical reactions of central importance in all living cells that use oxygen as part of cellular respiration.
TCA cycle
Summary
Pyruvate
It is a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer of H+ ions across a membrane
These H+ ions are used to produceATP, as they move back across the membrane.
Summary
NADH
Direct product 2 NADH 2ATP 2 NADH (mitochondrial matrix) 6 NADH (mitochondrial matrix) 2 FADH2 2 ATP
Final ATP 4 or 6 2 6 18 4 2
Release of Ca2+ through voltageor Ca2+-sensitive channel activates contraction Pumps induce relaxation
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 antagonist molecules that block Ca2+ channel activity
At rest tropomyosin blocks the myosin binding sites on actin. When calcium binds to the troponin complex a conformational change results in the movement of the tropomyosintropinin complex and exposure of actins myosin binding sites.
An individual muscle cell either contracts completely or not all. Individual muscles, composed of many individual muscle fibers, can contract to varying degrees. One way variation is accomplished by varying the frequency of action potentials reach the muscle from a single motor neuron.
Graded muscle contraction can also be controlled by regulating the number of motor units involved in the contraction
Recruitment of motor neurons increases the number of muscle cells involved in a contraction
Some muscles, such as those involved in posture, are always at least partially contracted Fatigue is avoided by rotating among motor units
In addition to skeletal muscle, vertebrates have 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.
Smooth muscle: lacks the striations seen in both skeletal and cardiac muscle
Contracts with less tension, but over a greater range 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
Ca2+ activates myosin light chain kinase (MLCK) which phosphorylates LC2, the regulatory light chain of myosin Ca2+ effect is via calmodulin - a cousin of Troponin C
Page 50 of 46
12/02/2008
Biochemistry: Muscles
Hormones regulate contraction epinephrine, a smooth muscle relaxer, activates adenylyl cyclase, making cAMP, which activates protein kinase, which phosphorylates MLCK, inactivating MLCK and relaxing muscle
55
1) Creatine phosphate
2) Cellular respiration
58
Anaerobic Phase
59
faster
60
Oxygen debt amount of oxygen needed by liver cells to use the accumulated lactic acid to produce glucose
oxygen not available glycolysis continues pyruvic acid converted to lactic acid liver converts lactic acid to glucose
61
muscle cells are major source of body heat blood transports heat throughout body
62
(angkat berat)
63
These differences are due primarily to the male sex hormone testosterone With more muscle mass, men are generally stronger than women Body strength per unit muscle mass, however, is the same in both sexes
With age, connective tissue increases and muscle fibers 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
Inability to contract
depletion of creatine phosphate decline of Ca+2 within the sarcoplasm Commonly caused from decreased blood flow insufficient oxygen or glycogen Ion imbalances across the sarcolemma Accumulation of lactic acid insufficient release of acetylcholine from motor neurons Cramp sustained, involuntary muscle contraction
66
Rigor mortis is a state of muscular rigidity that begins 3-4 hours after death and lasts about 24 hours After death, Ca+2 ions leak out of the SR and allow myosin heads to bind to actin Since ATP synthesis has ceased, crossbridges cannot detach from actin until proteolytic enzymes begin to digest the decomposing cells.
67