Muscles and Metabolism How does the body provide the energy needed for contraction? -as muscles contract, ATP supplies the energy fro cross bridge movement and detachment and for operation of the calcium pump in the sarcoplasmic reticulum -muscles store only 4 to 6 seconds' worth of ATP reserves (usually just enough energy to begin movement) -since ATP is the only energy source used directly for contractile activities, it must be regenerated as fast as it is broken down in order for contraction to continue -after ATP is hydrolyzed to ADP and inorganic phosphate in muscle fibres, it is regenerated quickly by 1 or more of these pathways: 1) Direct phosphorylation of ADP to creatine phosphate -during vigorous activity, the demand for ATP soars and the ATP stored in working muscles is consumed within a few twitches -creatine phosphate (CP), a unique high-energy molecule stored in muscles, is used to regenerate ATP while the metabolic pathways are adjusting to the suddenly higher demands for ATP -the result of coupling CP with ADP is an almost instant transfer of energy and a phosphate group from CP to ADP to form ATP creatine phosphate + ADP -----creatine kinase-----> creatine + ADP -muscle cells store 2 to 3 times as much CP as ATP and the CP-ADP reaction, catalyzed by creatine kinase, is so efficient that the amount of ATP in muscle cells changes very little during the initial period of contraction -together, stored ATP and CP provide maximum muscle power for 14-16 seconds -the coupled reaction is readily reversible and to keep CP readily available, CP reserves are replenished during periods of rest or inactivity 2) Glycolysis (an anaerobic pathway) which converts glucose to lactic acid -when stored ATP and CP become exhausted, more ATP is generated by breakdown (catabolism) of glucose obtained from the blood or of glycogen stored in the muscle -the initial phase of glucose breakdown is called glycolysis (sugar splitting) -this pathway occurs in both the presence and absence of oxygen -it does not use oxygen so it is anaerobic -during glycolysis, glucose is broken down to two pyruvic acid molecules, releasing enough energy to form small amounts of ATP (2 ATP per glucose) -normally, pyruvic acid produced during glycolysis enters the mitochondria and reacts with oxygen to produce more ATP (aerobic respiration) -when muscles contract vigorously and contractile activity reaches about 70% of the maximum possible, the bulging muscles compress the blood vessels within them, impairing blood flow and oxygen delivery
-under these anaerobic conditions, most of the pyruvic acid produced during glycolysis is converted into lactic acid and the overall process is referred to as anaerobic glycolysis -most of the lactic acid diffuses out of the muscles into the bloodstream and is gone from the muscle tissue within 30 minutes after exercise stops -the lactic acid is picked up by the liver, heart, or kidney cells which can use it as an energy source -liver cells can reconvert it to pyruvic acid or glucose and release it back into the bloodstream for muscle use or convert it to glycogen storage -the anaerobic pathway harvests only 5% as much ATP from each glucose molecule as the aerobic pathway, but it produces ATP 2.5x faster -when large amounts of ATP are needed for moderate periods (30-40 seconds of muscle activity), glycolysis can provide most of the ATP needed as long as the required fuels and enzymes are available -together, stored ATP and CP and the glycolysis-lactic acid pathway can support strenuous muscle activity for nearly a minute -in anaerobic glycolysis, huge amounts of glucose are used to produce relatively small harvests of ATP and the accumulation of lactic acid is partially responsible for muscle soreness 3) Aerobic Respiration -during rest and light/moderate exercise (even if prolonged) 95% of ATP used for muscle activity comes from aerobic respiration -occurs in the mitochondria, requires oxygen, and involves a sequence of chemical reactions in which the bonds of fuel molecules are broken and the energy released is used to make ATP -aerobic respiration includes glycolysis and the reactions that take place in the mitochondria -glucose is broken down entirely, yielding water, carbon dioxide, and large amounts of ATP -as exercise begins, muscle glycogen provides most of the fuel -shortly after, bloodborne glucose, pyruvic acid from glycolysis, and free fatty acids are the major source of fuels -after about 30 minutes, fatty acids become the major energy fuels -aerobic respiration provides a high yield of ATP (32 ATP per glucose) but it is slow because of its many steps and it requires continuous delivery of oxygen and nutrient fuels to keep it going Which pathways predominate during exercise? -if there is enough oxygen, a muscle cell will form ATP by the aerobic pathway
-when ATP demands are within the capacity of the aerobic pathway, light to moderate muscular activity can continue for several hours in well-conditioned individuals -when exercise demands begin to exceed the ability of the muscle cells to carry out the necessary reactions quickly enough, glycolysis begins to contribute more and more of the total ATP generated aerobic endurance- the length of time a muscle can continue to contract using aerobic pathways anaerobic threshold- the point at which muscle metabolism converts to anaerobic glycolysis -activities that require a surge of power but last only a few seconds (weight lifting, diving, and sprinting) rely entirely on ATP and CP stores -on and off burst-like activities (tennis, soccer, 100 meter swimming) appear to be fuelled almost entirely by anaerobic glycolysis -prolonged activities such as marathon runs and jogging, where endurance is the goal, depend mainly on aerobic respiration -levels of CP and ATP don't change much during prolonged exercise since ATP is generated at the same rate as it is used -aerobic generation of ATP is relatively slow but the ATP harvest is enormous Muscle Fatigue -physiological inability to contract even though the muscle still may be receiving stimuli -fatigue is due to a problem in excitation-contraction coupling or in more rare cases, problems at the neuromuscular junction -ATP is not a fatigue-producing factor in moderate exercise since ATP will not totally run out -a total lack of ATP results in contractures (state of continuous contraction because cross bridges are unable to detach (cramps) -severe ionic imbalances contribute to muscle fatigue -as action potentials are transmitted, potassium is lost from the muscle cells and the Na+ - K+ pumps are inadequate to reverse the ionic imbalances quickly, so K+ accumulates in the fluids of the T tubules -this ionic change disturbs the membrane potential of the muscle cell and halts Ca2+ release from the sarcoplasmic reticulum -in short duration exercise, an accumulation of inorganic phosphate from CP and TP breakdown may interfere with calcium release from the SR or alternatively with the release of Pi from myosin and thus hamper myosin's power strokes
-lactic acid has been assumed to be a major cause of fatigue, but it seems to be more important in provoking central, psychological fatigue (rather than physiological fatigue), where muscles are still willing to "go" but we feel too tired to continue the activity -in general, intense exercise of short duration produces fatigue rapidly via ionic disturbances that alter E-C coupling, but recovery is also rapid -in short duration exercise, the slow-developing fatigue of prolonged low-intensity exercise may require several hours for complete recovery -this type of exercise damages the SR, interfering with Ca2+ regulation and release, and therefore with muscle activation Oxygen Deficit / Oxygen Debt -for a muscle to return to its resting state, its oxygen reserves must be replenished, the accumulated lactic acid must be reconverted to pyruvic acid, glycogen stores must be replaced, and ATP and creatine phosphate reserves must be resynthesized -the liver must convert any lactic acid persisting in blood to glucose or glycogen -during anaerobic muscle contraction, all of these oxygen-requiring activities occur more slowly and are deferred until oxygen is available again oxygen deficit- the extra amount of oxygen that the body must take in for these restorative processes; the difference between the amount of oxygen needed for total aerobic muscle activity and the amount actually used -all anaerobic sources of ATP used during muscle activity contribute to this deficit Heat Production During Muscle Activity -only about 40% of the energy released during muscle contraction is converted to useful work; the rest is given off has heat -ATP driven muscle contraction is 20-25% efficient Force of Muscle Contraction -the force of muscle contraction is affected by: 1) the number of muscle fibres stimulated -the more motor units that are recruited, the greater the muscle force 2) the relative size of the fibres -the bulkier the muscle (the greater its cross-sectional area), the more tension it can develop and the greater its strength -the larger fibres of large motor units are effective in producing the most powerful movements -regular resistance exercise increases muscle force by causing muscle cells to hypertrophy (increase in size)
3) the frequency of stimulation -the more rapidly a muscle is stimulated, the greater the force it exerts 4) the degree of muscle stretch -the ideal length-tension relationship occurs when a muscle is slightly stretched and the thin and thick filaments overlap optimally, because this relationship permits sliding along nearly the entire length of the thin filaments -if a muscle fibre is stretched so much that the filaments do not overlap, the myosin heads have nothing to attach to and cannot generate tension -if sarcomeres are so compressed and cramped that the Z discs abut the thick myofilaments, and the thin filaments touch and interfere with one another, little or no further shortening can occur Muscle Fibre Types 1) Speed of Contraction -there are slow fibres and fast fibres in terms of the speed of shortening or contraction -the difference in speed reflects how fast their myosin ATPases split ATP and on the patter of electrical activity of their motor neurons -duration of contraction also varies with fibre type and depends on how quickly Ca2+ is moved from the cytosol into the SR 2) Major pathways for forming ATP - the cells that rely mostly on oxygen-using aerobic pathways for ATP generation are oxidative fibres and those that rely on anaerobic glycolysis are glycolytic fibres -using these 2 criteria, skeletal muscle cells can be classified as being slow oxidative (SO) fibres, fast oxidative (FO) fibres, or fast glycolytic (FG) fibres Slow oxidative (SO) fibres -contracts slowly since its myosin ATPases are slow -depends on oxygen delivery and aerobic pathways (high-oxidative capacity) -fatigue resistant; has high endurance (aerobic metabolism) -thin; has a large amount of cytoplasm that impedes diffusion of O2 and nutrients from the blood -little power (a thin cell can contain only a limited number of myofibrils) -has many mitochondria -rich capillary supply -red (color is due to abundant myoglobin, muscle's oxygen-binding pigment that stores O2 reserves in the cell and aids diffusion of O2 through the cell) -muscle fibres are best suited to endurance-type activities Fast glycolytic (FG) fibres -contracts rapidly due to activity of fast myosin ATPases -does not use oxygen
-depends on glycogen reserves for fuel rather than on blood-delivered nutrients -tires quickly since glycogen reserves are short-lived and accumulation of lactic acid -large diameter fibres with plentiful contractile myofilaments -few mitochondria and low capillary density -thicker cell; doesn't depend on continuous oxygen and nutrient diffusion from the blood -suited for short term, rapid, intense movements Fast oxidative (FO) fibres -less common intermediate muscle fibre -contract quickly but are oxygen dependant and have a rich supply of myoglobin and capillaries -fatigue resistant Adaptations to Exercise -aerobic or endurance exercise such as swimming, jogging, etc. result in an increase in the number of capillaries surrounding the muscle fibre and in the number of mitochondria within them, and the fibres synthesize more myoglobin -the changes are most dramatic in slow oxidative fibres which depend primarily on aerobic pathways -resistance exercise allows for muscle hypertrophy where the size of individual muscle fibres increase Smooth Muscle -the muscles in the walls of all the body's hollow organs (except the heart) is almost entirely made up of smooth muscle -smooth muscle fibres are spindle-shaped cells of variable size, with a centrally located nucleus (skeletal muscle fibres are up to 10 times wider and thousands of times longer) -smooth muscles lack the coarse connective tissue sheaths seen in skeletal muscle -endomysium secreted by smooth muscles containing blood vessels and nerves is found between smooth muscle fibres -smooth muscle is organized into sheets of closely opposed fibres and occur in all but the smallest blood vessels and in the walls of hollow organs -2 sheets of smooth muscle are present and their fibres are oriented at right angles to each other -the longitudinal layer has muscle fibres that run parallel to the long axis of the organ; when the muscle contracts, the organ dilates and shortens -the circular layer has muscle fires that run around the circumference of the organ; contractions of this layer constricts the cavity of the organ and cases it to elongate -the alternating contraction and relaxation of these opposing layers mixes substances in the lumen and squeezes them through the organ's internal path or peristalsis -smooth muscle lack neuromuscular junctions; the innervating nerve fibres (part of the ANS) have bulbous swellings called varicosities which release neurotransmitter into a
wide synaptic cleft in the general area of the smooth muscle cells; these junctions are called diffuse junctions -the sarcoplasmic reticulum of smooth muscle fibres is much less developed than that of skeletal muscle and lacks a specific pattern relative to the myofilaments -some SR tubules of smooth muscle touch the sarcolemma at several sites -T tubules are absent but the sarcolemma of the smooth muscle fibre has multiple caveolae (pouch-like infoldings that sequester bits of extracellular fluid containing high concentrations of Ca2+ close to the membrane) -when calcium channels in the caveolae open, Ca2+ influx occurs rapidly -there are no striations nor sarcomeres -thick filaments are fewer but have myosin heads along their entire length -the ratio of thick to think filaments is much lower compared to skeletal muscle (1:13 compared to 1:2) -thick filaments of smooth muscle contain actin-gripping myosin heads along their entire length which allows smooth muscle to be as powerful as a skeletal muscle of the same size -no troponin complex in thin filaments -no troponin complex is present in smooth muscle; instead, a protein called calmodulin acts as the calcium-binding site -there is tropomyosin but no troponin -thick and thin filaments arranged diagonally -bundles of contractile proteins crisscross within the smooth muscle cell so they spiral down the long axis of the cell like the strips on a barber pole -this allows the smooth muscle cells to contract in a twisting way so thaty they look like tiny corkscrews -intermediate filament-dense body network -smooth muscle fibres contain a lattice-like arrangement of non-contractile intermediate filaments that resist tension -they attach at regular intervals to dense bodies (cytoplasmic structures) -dense bodies, which are also connected to the sarcolemma, act as anchoring points for thin filaments and correspond to Z discs of skeletal muscle Special Features of Smooth Muscle Contraction 1) Response to Stretch -responds with more vigorous contractions -stretching provokes contraction which automatically moves substances along an internal tract and the muscle adapts to its new length and relaxes while retaining the ability to contract on demand
-stress-relaxation response allows hollow organs to fill or expand slowly to accommodate a greater volume without promoting strong contractions 2) Length and Tension Changes -smooth muscle stretches more than skeletal muscle and can generate more tension than skeletal muscles when stretched to a comparable extent -the lack of sarcomeres and irregular arrangement of smooth muscle filaments allow them to generate considerable force even when substantially stretched -smooth muscle can undergo a total length change of 150% and still function while skeletal muscle can only undergo a length change of 60% 3) Hyperplasia -certain smooth muscle fibres can divide to increase their numbers (hyperplasia) e.g.: the response of the uterus to estrogen Single-Unit Smooth Muscle -visceral muscle -found in the walls of hollow organs except the heard -arranged in opposing (longitudinal and circular) sheets -innervated by ANS varicosities -are electrically coupled gap junctions and contract as a unit -respond to various chemical stimuli Multi-Unit Smooth Muscle -smooth muscle in the large airways to the lungs, in large arteries, the arrector pili muscles attached to hair follicles, the internal eye muscles that adjust pupil size and allow the eye to focus visually -gap junctions, spontaneous synchronous depolarizations are rare -consists of muscle fibres that are structurally independent of one another -richly supplied with nerve endings which forms a motor unit with a number of muscle fibres -responds to neural stimulation with graded contractions that involve recruitment -innervated by the ANS and responsive to hormonal controls