Exercise biochemistry Skeletal muscle • Muscle – One of 4 principle tissue of the body • Muscle, nerve, connective, epithelial – 3 forms • Skeletal, smooth, cardiac – Only skeletal is voluntary – Function • Exerts force (for locomotion) – Energy is chemical • Other functions – – – – Heat production Posture Protection Shape Muscle structure • Muscle layers – Epimysium • Surrounds whole muscle – Perimysium (fascia) • Surrounds (bundles of fibers) – Endomysium • Surrounds individual muscle fibers • Each muscle fiber – One nerve ending • Motor endplate – Connection between muscle fiber and nerve • Neurotransmitter – Acetylcholine (Ach) • Muscle blood flow – Capillaries surround the muscle fibers • Travel in 3 dimensions • Capillaries are very “tortuous” • Capillaries are fed by an arteriole – Great ability to adapt to changes in work – Skeletal muscle blood flow • Can increase markedly from rest to maximal exercise • This is dependent upon the muscle type – Slow twitch » Large capacity to increase flow – Fast twitch » Oxidative; moderate ability to increase flow » Glycolytic; poor ability to increase flow Muscle structure Muscle fiber structure Myocytes • Multinucleated • Thin •10-100 µm •Length varies •3 mm to 30 cm •Interior •Sarcoplasm •Mitochondria, myoglobin (gives muscle it’s “red” appearance) and myofibrils •Sarcoplasmic reticulum •Surrounds myofibrils •Growth, repair, maintenance •T-tubules •Involved in nerve transmission and calcium release Muscle fiber structure • Skeletal muscle has a unique “banded” appearance – Due to “Dark” A bands and “Light” I bands • A bands: Myosin and actin – Anisotropic: different properties in different directions • I bands: just actin – Isotropic: Same properties in all directions – H zone • Light zone (“helle”) that contains M line (middle) • No overlap between actin and myosin – Z disc • Separate sarcomeres • When actin connects • Also connects adjacent myofibrils Molecular composition of the myofilaments • Myosin filament – Rod-like tail with two heads • ATPase located here – Interacts with actin • Globular (G actin) and fibrous (F actin) • Tropomyosin – Stiffens the actin filament • Troponin – Troponin I: Binds to actin – Troponin T: Binds to tropomyosin – Troponin C: binds calcium • Force development – Sarcomeres shorten • Actin and myosin slide over one another – Calcium allows tropomyosin to move “Unblocking” actin • Ca2+ binds to troponin C – Myosin interacts with actin (1) – Myosin head moves actin • ADP + Pi are released (2) – ATP binds to myosin head • Allows myosin to disengage from actin (3) – ATP is broken down • This allows for myosin head movement (4) – Cycle starts again Force development Control of force development 2 1) Neurotransmitter release – Acetylcholine 1 2) Action potential propagation – Sarcolemma to T-tubules 3) Calcium release – 6 Terminal cisternae of SR 4) Calcium concentration rises in sarcoplasm – Binds to troponin C • Causes tropomyosin shift 5) Contraction occurs 6) Calcium resequestered – – 3 When neural stimuli ceases Tropomyosin blockage restored 4 5 Motor units • A motor neuron and the fibers it innervates – Number of fibers varies • Muscle that perform very fine movements (eye, hands) – Small motor units • Muscle involved in larger movements – Large motor units • All or none – A stimulus will either activate the entire motor unit, or none of it Muscle fiber types • Type 1 – Slow twitch, very high fatigue resistance, used for prolonged activity, red • Type 2 – Two types • Type 2a, fast-twitch oxidative, intermediate fatigue resistance, used for longer high intensity exercise • Type 2b, fast-twitch glycolytic, fast to fatigue, used for very brief high intensity contractions Muscle fiber types • Size principle – Larger fiber types recruited as intensity increases • Type 1, type 2a, type 2b • Human muscle contains a mixture of fiber types – Postural muscle • High proportion of type 1 – Rapid movement muscle • Hand and eye – High proportion of type 2 – Many are mixed fiber muscle • Quadriceps • This seems to be determined primarily at birth – Distance runners have a high percentage of type 1 fibers – Sprinters, type 2 Types of muscle action • Concentric contraction – Muscle shortens while developing force • Eccentric “contraction” – Muscle lengthens while generating force • Isometric contraction – Muscle generates force with no change in length Plasticity of muscle • Plasticity – Ability to adapt • Alterations in – Size – Fiber composition (small) – Metabolic capacity – Capillary density Sources of energy for muscular contraction • Adenosine triphosphate – Provides the energy for muscular contraction 1) ATP↔ADP +Pi + energy – ATPase 2) PCr + ADP ↔ ATP + Cr – Reactions 1 and 2 work together 3) Anaerobic metabolism of glucose – Yields lactate and small amt of ATP 4) Aerobic metabolism of CHO, fast and proteins – Aerobic metabolism yields lots of ATP, but it is slow Phosphagen system Energy systems • Immediate energy system – Phosphagen system • Relies on Phosphocreatine (PCr) to quickly resynthesize ATP • PCr + ADP ↔ ATP + Cr – Creatine kinase • Resynthesizes ATP very fast • Very small amounts of ATP and PCr stored in the muscle – Enough for about 10s of activity Glycolytic system • Since most activity lasts longer than 10s or so, need another system – Glycolytic system • Uses glucose or glycogen • Glycolysis – Breaks down glucose to 2 pyruvate molecules • Anaerobic glycolysis – Pyruvate is converted to lactate – Small amount of ATP • Allows work to continue for about 2-5 minutes – Dependent upon pain tolerance Aerobic metabolism • Requires – Mitochondria, oxygen – Can use • Carbohydrates, fats or proteins – Huge capacity • Virtually unlimited – Slow ATP delivery • Sustains long-term, lowintensity work Tricarboxylic acid cycle • AKA – Kreb’s cycle and Citric acid cycle • Function – Break down Acetyl-CoA to CO2 and H+ – Also forms small amount of ATP – H+ carried by • NADH and FADH2 • To ETC • Net production – 1 ATP (GTP transfers terminal P to ADP; nucleotide diphosphokinase) – 3 NADH – 1 FADH2 Tricarboxylic acid cycle • 1st step – Formation of citrate – Citrate synthase • 2cd step – Formation of isocitrate – Isomer of citrate • 3rd step – Formation of alphaketoglutarate – Isocitrate dehydrogenase – 1 NADH • 4th step – Formation of Succinyl CoA – Alpha-ketoglutarate dehydrogenase – 1 NADH Tricarboxylic acid cycle • 5th step – Formation of succinate – Succinyl-CoA synthetase – 1 ATP • 6th step – Formation of fumarate – Succinate dehydrogenase – 1 FADH2 • 7th step – Formation of malate • 8th step – Formation of oxaloacetate – Malate dehydrogenase – 1 NADH Tricarboxylic acid cycle • Summary – Acetyl-CoA + ADP + 3NAD+ + FAD ↔ 2CO2 + ATP + 3NADH + 3H+ + FADH2 + CoA – Citrate synthase • Key regulatory enzyme – Inhibited by » ATP, NADH, Succinyl-CoA » Thus, when cellular energy state is HIGH, TCA cycle is inhibited – Stimulated by » ADP, NAD+, Acetyl-CoA • Basically – Stimulated by substrate, inhibited by products Electron transport chain • Linked proteins which remove the electrons from H+ • This separates the charge and creates, in essence, a molecular battery • This charge difference powers the formation of ATP • The electrons (and H+) then combine with molecular O2 to form H2O Electron transport chain • NAD and FAD – Electron (and H+) carriers – So much of metabolism is providing an electro-chemical charge difference across the inner membrane of the mitochondria to drive ATP formation Electron Transport Chain • Step 1 – NADH dehydrogenase complex – 2 e- transferred to FMN to form FMNH2 • 1 ATP formed • Step 2 – Coenzyme Q – Accepts e- from FADH2 • Step 1 and 2 – Dropping off H+ and e- Electron transport chain • Step 3 – Cytochrome chain – Electrons are transferred from CoQ to each cytochrome • Cytochrome b • Cytochrome c – 1 ATP • Cytochrome oxidase – 1 ATP • Step 3 summary – Electron transport and ATP formation (oxidative phosphorylation) • Glycogen: – Storage form of glucose • Muscle (~350g) , liver (~80g) and blood (~5g of glucose) – Total (70 kg man; 15% bodyfat) » ~435g • Lipids – Stored primarily in adipocytes • Also in muscle and around organs as well circulating in blood (Fatty acids) – ~10,500g • Marathon – Requires ~2900-3000 kcal of energy – Requires about 750g of CHO – Only requires ~ 330g of fat Energy storage Energy storage
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