Vitamins K and C Block Head Neck Structure

• Vitamins K and C Block: Head & Neck Structure and Function Biochemistry Lecture: Muscle contraction: W a f i k

Muscle contractions: q. List the main biochemical components of muscle fiber & list its organelles in relation to their functions in muscle contraction. q. List the main proteins composing the structure of sarcomere & describe the function of each. q. List the main proteins composing thin & thick filaments & their relationships in skeletal muscles. q. List the main accessory proteins that play an important role in muscle structure & function. Emphasize the function of dystrophin and related proteins. q. Outline the biochemical events that occur during one cycle of muscle contraction & list the determinants that lead to relaxation. q. List the different sources of energy for muscle contraction. W a f i k q. Describe the role of calcium ions in muscle contraction & relaxation

A- List the main contractile proteins of of muscle fiber The mass of a muscle is made up of 75% water and more than 20% protein. Muscle proteins Function 1 -Myosin Acts as a linkage between microfilaments and the cell membrane. Hydrolysis of ATP during contraction of the muscle Force transduction 2 -Actin binds myosin to form actomyosin (actin-myosin) during muscle contraction 3 -Tropomyosin It is attached to F-actin in the groove between its filaments to block myosin binding sites W a f i k 4 -Troponin Binding Ca + + during muscle contraction

B-List muscle fiber organelles (biochemical structures) in relation to their functions in muscle contraction. 1 -Functional units of myofibrils is sarcomeres that has: 1) cytoplasm called sarcoplasm that contain • Glycogen • ATP, and phosphocreatine • Enzymes of glycolysis 2) Sarcoplasmic reticulum contains calcium to conduct nerve impulses. 3) The muscle cell is called a muscle fiber with plasma membrane called sarcolemma 4) Many nuclei and mitochondria (sarcosome) W a f i k

2 -A band: Dark band seen as part of striation (anisotropic band) 3 -I band: light band area between the ends of the myosin (isotropic band) 4 -Z-line: Membrane that separates sarcomeres 5 -H zone: Area by which the two ends of the thin filaments fail to meet 6 -Sarcomere is the functional unit composed of two myofilaments • Thick filaments (myosin) • Thin filaments (actin- tropinin-tropomyosin) W a f i k

The main proteins composing the structure of sarcomere & functions 1 -Thick filament that contain myosin protein (dark band) It contains myosin-binding protein C which binds at one end to the thick filament and the other to Actin. 2 -Thin filaments are composed of: 1) Actin : It is globular protein formed of (G-actin & F-actin) Function: Actin forms cross bridges with myosin during muscle contraction. 2) Tropomyosin: It is a fibrous protein of two chains, alpha and beta, Function: it is attached to F-actin in the groove between its filaments to block myosin binding sites 3) Troponin complex: three polypeptides Troponin T which binds to tropomyosin Troponin I, inhibits the F-actin-myosin interaction binding during absence of Ca+2 of relaxed Striated Muscle. W a f i k Troponin C: calmodulin for calcium

Main outline structure of sarcomere W a f i k

Main accessory proteins that play an important role in muscle structure & function 1)Titin 2)Nebulin 3)a-Actinin 4)Desmin 5)Dystrophin 6)Calcineurin 7)Myosin-. binding protein C Functions: 1) Help in relaxation of muscle. 2) Regulate assembly length of actin and filaments 3) Stabilization of actin filaments. W a f i k 4) Maintaing structure of sarcomeres

Dystrophin is a cytoplasmic accessory protein, Function: 1 -They connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. 2 - Stabilizaton of membrane during contraction & relaxation W a f i k

• Main proteins composing thin & thick filaments & their relationships in skeletal muscles. 1 -(Myosin= Thick Filaments) ü It is an asymmetric hexamer consists of one pair of heavy chains and two pairs of light chains ü Myosin has a fibrous tail consisting of two intertwined helices. ü Each helix has a globular head portion Function: üGlobular head drives movement of actin filaments past myosin filaments. üRegulating ATPase functions depending on their phosphorylation status. W a f i k

Thin Filaments =Actin 1. It is monomeric or globular (G) actin, that upon addition of salts 2. At physiological concentrations) G actine is polymerized to a highly viscous gel (filamentous or fibrous (F) actin 3. Thin filaments contain the proteins actin, tropomyosin, and troponin Function: 1) G-actin binds globular myosin heads 2) They inhibit the interaction between actin and myosin during relaxation W a f i k

Sources of energy for muscle contraction (energy metabolism). ØCreatine phosphate Skeletal muscle contains phosphocreatine, which acts as an energy store for short-term (seconds) demands. ØSkeletal muscle cannot contribute directly to blood glucose because it does not contain glucose-6 -phosphatase. ØAnaerobic metabolism in skeletal muscle produce Lactate (anaerobic glycolysis) then passes to liver to synthesize glucose, which can then return to muscle (the Cori cycle). ØIn the fed state, most glucose is used to synthesize glycogen ØProlonged starvation Free fatty acids & ketone bodies are a major source of energy Proteolysis supplies amino acids for gluconeogenesis. ØMetabolism of branched-chain amino acids W a f i k

ØMajor amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). ØEpinephrine stimulates glycogenolysis in skeletal muscle, whereas Glucagon does not because of absence of its receptors. Insulin acts on skeletal muscle to increase uptake of glucose ØActin, myosin, troponin complex (Tp. T, Tpl, and Tp. C), ATP, and Ca 2+ are key constituents in relation to contraction. ØThe Ca 2+ ATPase, the Ca 2+ release channel, and calsequestrin are proteins involved in various aspects of Ca 2+ metabolism in muscle. W a f i k

Biochemical events that occur during one cycle of muscle contraction & list the determinants that lead to relaxation Muscle contraction subject to fine regulation via the nervous system (1)Discharge of motor neuron (2) Release of transmitter (acetylcholine) at motor endplate then binding receptors (3) Increased Na+ and K+ conductance in endplate membrane W a f i k

Steps in Muscle Contraction (Resting sarcomere) Step 1: Head of myosin hydrolyzes ATP to ADP and Pi to result ADP-Pi- myosin complex (high-energy conformation. ) Step 2: (in response to nerve/Ca 2+ stimulation) Ca+ binds to troponin exposing active site on actin forming actinomycin complex Then binding to ADP-Pi- myosin complex Step 3: Promotes the release of Pi, which initiates the power stroke (conformational change in myosin heads ), then release of ADP Pulling of crossbridge actin towards center of sarcomere (shortening ) W a f i k

Step 4: Myosin head binds another ATP Forming an actin-myosin-ATP complex. Step 5: (key component of relaxation) Myosin-ATP has a low affinity for actin, and actin is thus released. In step 4: If intracellular levels of ATP drop (eg, after death), ATP does not bind myosin head (step 4 above), and actin does not dissociate, and relaxation (step 5)does not occur. W a f i k

Steps in relaxation Step 1: Ca 2+ pumped back into sarcoplasmic reticulum by Ca 2+ ATPase Step 2: Release of Ca 2+ from troponin. C Step 3: Troponin, via interaction with tropomyosin, inhibits further myosin head and F-actin interaction. Step 4: Presence of ATP, myosin head lead to release of F-actin. Step 5: The end of interaction between actin and myosin W a f i k

The role of calcium ions in muscle contraction & relaxation During contraction 1) Sarcolemma depolarization: Spreads to internal T tubule system 2) Ca 2+ is released from the SR and from the extracellular space 3) Ca 2+ interacts with calmodulin (Tp. C) and myosin light chain kinase to activate myosin (uncovering of myosin binding sites). 4) Activated calmodulin activates the Myosin/ATPase (kinase) 5) Activated kinase transfers phosphate from ATP to myosin cross bridges 6) Phosphorylated cross bridges interact with actin to produce shortening (contraction) W a f i k

During relaxation: 1) Sarcoplasmic Ca + + reduced and pumped into the SR by ATP-driven Ca + + pump 2) Troponin and tropomyosin, inhibits myosin head and F-actin interaction (covering of myosin binding sites) , and in the presence of ATP the myosin head detaches from the F-actin. Reference: Harper’s Illustrated Biochemistry Chapter 49: Muscle & the Cytoskeleton W a f i k