Exercise biochemistry

Skeletal muscle Muscle 3 forms Only skeletal is voluntary Function 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 Each muscle fiber 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 structure 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 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 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

Control of force development 2 Neurotransmitter release Acetylcholine Action potential propagation Sarcolemma to T-tubules Calcium release Terminal cisternae of SR Calcium concentration rises in sarcoplasm Binds to troponin C Causes tropomyosin shift 5) Contraction occurs Calcium resequestered When neural stimuli ceases Tropomyosin blockage restored 1 6 3 4 5

Motor units A motor neuron and the fibers it innervates All or none 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 Type 2 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 Eccentric “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 Resynthesizes ATP very fast 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 Huge capacity Carbohydrates, fats or proteins Huge capacity Virtually unlimited Slow ATP delivery Sustains long-term, low-intensity 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 alpha-ketoglutarate Isocitrate dehydrogenase 1 NADH 4th step Formation of Succinyl CoA Alpha-ketoglutarate dehydrogenase

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 Step 3 summary Electron transport and ATP formation (oxidative phosphorylation)

Energy storage Marathon Glycogen: Lipids 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