Module 3 Fuel for Exercising Muscle PDF

Module 3: Fuel for Exercising Muscle 1 Learning Objectives ¨Learn how our bodies change the food we eat into ATP to provide our muscles with the energy they need to move. ¨Examine three metabolic systems that generate ATP for muscles. ¨Explore how e...

Module 3: Fuel for Exercising Muscle 1 Learning Objectives ¨Learn how our bodies change the food we eat into ATP to provide our muscles with the energy they need to move. ¨Examine three metabolic systems that generate ATP for muscles. ¨Explore how energy production and availability can limit performance. ¨Learn how exercise affects metabolism and how metabolism can be monitored to determine energy expenditure. 2 Calorie/kilocalorie/kilojoule w Energy in biological systems is measured in kilocalories (kcal).  1 kcal is the amount of heat energy needed to raise 1kg of water 1°C from 14.5°C to 15.5°C.  kcal is a measure of heat energy  1 kilojoule is the amount of energy expended when 1 kg is moved 1 metre by a force of 1 newton  kJ is a measure of work energy 1,00 calories = 1 kilocalorie = 1 Calorie (dietary) 1 kcal = 4.2 kJ How many kcal are in CHO, protein, fat, alcohol per gram?3 _____ a reaction in which electrons are removed from a molecule. This occurs Definitions (Review) when a molecule reacts with oxygen 1. Metabolism _____ the sum total of all the chemical reactions that go on in living cells 2. Gluconeogenesis _____ all the reactions the body 3. Glycolysis obtains and uses energy from food 4. Bioenergetics _____ glucose synthesis from fat or 5. Energy Metabolism protein 6. Oxidation _____ glucose to glycogen 7. Glycogenesis _____ glycogen to glucose _____ glucose to pyruvate 8. Adenosine _____ _energy Triphosphate ______the process where each cell 9. Glycogenolysis contains chemical pathways that convert nutrients from food to usable energy 4 Energy Sources for the Body w At rest and longer less intense exercise, the body uses ________________ and _________________ for energy. w ______________________ provides very little energy for cellular activity but serves as building blocks for the body's tissues. w During moderate to severe muscular effort, the body relies mostly on ________________________ for fuel 5  Energy Contribution of Substrates During Exercise Activity Rest Light- High- High-Int Mod Int Enduranc Intensity Sprint e Glucose/ 30 - 35% 40 - 95% 70 – Glycoge 45% 80% n Protein 2-5% 2-5% 2% 5-10% Fat 60 - 65% 55% 3% 15% 6 Blood Glucose Uptake by the Leg Muscles Affected by Exercise Duration and Intensity At any % of maxVO2, the use of CHO for exercise: As TIME ↑, more glucose is being utilized (compared to rest) As exercise INTENSITY ↑ (%max VO2) more glucose is used 10 minute spike 7 Body Stores of Fuels and Associated Energy Availability 8 Enzymes w Specific protein molecules that control the breakdown of chemical compounds w Names end in “ase” w Work at different rates and can limit a reaction  Glycolytic enzymes act in the cytoplasm  Oxidative enzymes act in the mitochondria 9 Basic Energy Systems 1. ATP-PCr system (phosphagen system) (cytoplasm) 2. Glycolytic system (cytoplasm) 3. Oxidative system (mitochondria) 10  ATP-PCr system (anaerobic metabolism) 11  Energy - Adenosine Triphosphate (ATP) Adenosine is adenine + ribose - Adenine is N based - Ribose is a 5 carbon monosaccharide A limited quantity of ATP serves as energy for the cells. At any one time, the body stores only about 80g – 100g of ATP. This provides only a few seconds (~3-15 sec at any given time) of energy for the muscle, therefore, ATP must be continually synthesized to meet energy 12 requirements.  The Generation of ATP (a) The structure of an adenosine triphosphate (ATP) molecule, showing the high-energy phosphate bonds. (b) When the third phosphate on the ATP molecule is separated from adenosine by the action of adenosine triphosphatase (ATPase), energy is released.13 How else can ATP be generated? ATP-PCr System w This system can prevent energy depletion by quickly reforming ATP from ADP and Pi. w This process is anaerobic.  1 molecule of ATP is produced per 1 molecule of phosphocreatine (PCr) or creatine phosphate (PC).  The energy from the breakdown of PCr is not used for cellular work but solely for regenerating ATP.  ATP and PCr sustain the muscle’s energy needs for approx 3 – 15 sec during all out exercise 14 RECREATING ATP WITH PCr Phosphocreatine is hydrolyzed by the enzyme creatine kinase. ADP is phosphorylated to ATP. Creatine may be phosphorylated back to PCr. Cells store approximately 3 to 5 times more PCr than ATP. 15 PCr - The Energy Reservoir 16 Changes in muscle ATP and PCr during 14s of maximal muscular effort (sprinting). Although ATP is being used at a very high rate, the energy from PCr is used to synthesize ATP, preventing the ATP level from decreasing. However, at exhaustion, both ATP and PCr levels are low. 17  Glycolytic System (glycolysis; anaerobic metabolism) 18  CHO Metabolism - Glycolysis Anaerobic metabolism Anaerobic respiration Glycolysis (means “splitting of sugar”) Glycolytic System The Embden-Meyerhof Pathway (discoverers) Glucose to pyruvate reactions that do not require oxygen 19  Glycolysis Simplified 2NAD 2NADH + 2H Note: There are many more steps in glycolysis. Note: Reversible pyruvate glucose 20  Glycolysis (glycogen ↔ glucose) Catabolic Reaction: Glycogen to Glucose (yields energy) Anabolic Reaction: Glucose to Glycogen (requires energy) Glycogen Glucose-1-Phosphate Galactose enters here hexokinase Glucose Glucose-6-Phosphate Glycolysis begins once glucose-6-phosphate is formed 21 Hexokinase catalyzes: glucose + ATP  glucose-6-phosphate + ADP  Anaerobic Glycolysis Glucose Glucose-6-phosphate Fructose-6-phosphate Fructose enters here PFK (phosphofructokinase) Fructose-1, 6-diphosphate 5 more steps Pyruvate LDH (lactate dehydrogenase) Lactate Enzymes 22 next slide  PFK and LDH Phosphofructokinase – Rate limiting enzyme – Inhibited by ATP – Inhibition of PFK prevents breakdown of glucose when ATP is plentiful, because it is more useful for the cell to store glucose as glycogen rather than use it when ATP is plentiful Lactase Dehydrogenase – Enzyme that converts pyruvate to lactate and lactate to pyruvate 23 Glycolytic System  1 molecule of glycogen produces 3 ATP  1 molecule of glucose produces 2 ATP (4 ATP is produced when glucose is split into two 3 carbon fragments)  The difference is due to the fact that it requires 1 ATP to convert glucose to glucose-6-phosphate, where glycogen is converted to glucose-1- phosphate and then to glucose-6-phosphate without the loss of 1 ATP. ATP-PCr and Glycolysis together can provide energy for approx 2 minutes of all-out exercise 24  CHO Metabolism – Cori Cycle If the cell still needs energy, and oxygen is not available, it converts pyruvate to lactic acid (until oxygen becomes available) glucose pyruvate lactic acid at this point, the exerciser’s body is said to be building up an oxygen debt During oxygen debt, pyruvate molecules accumulate, and oxygen is needed faster than it can be delivered to break them down completely 25  Cori Cycle Glycolysi Gluconeogenesis s NAD NADH + H NAD Because very little ATP is produced, the Cori Cycle cannot sustain physical exertion for very long, muscle fatigue occurs relatively 26 quickly.  Pathway of the Cori Cycle - Overview The Cori Cycle not only removes lactate, but uses it to resynthesize glucose and subsequently muscle glycogen (gluconeogenesis) Muscle  Glucose  Pyruvate  Lactate Lactate travels to the liver Lactate  Glucose Glucose returns to muscle Glucose  Muscle Glycogen 27 NAD – Nicotinamide Adenine Dinucleotide Glyceraldehyde-3-phosphate Dehydrogenase catalyzes: glyceraldehyde-3-phosphate + NAD + Pi  1,3,bisphosphoglycerate + NADH + H This is the only step in Glycolysis in which NAD is reduced to NADH + H. 28 NAD in glycolysis 29  Lactate Formation In strenuous exercise, when energy demands exceed either O2 supply or utilization rate, the respiratory chain cannot process all of the H joined to NADH. Rapid release of energy in glycolysis depends on NADH otherwise the rapid rate of glycolysis stops. fructose 1,6-diphosphate NAD NADH + H 1, 3-diphosphoglycerate 30  Lactate Formation Lactate forms when excess hydrogens from NADH combine temporarily with pyruvate. This frees up NADH2 to accept additional H generated in glycolysis. Lactate dehydrogenase (LDH) drives this reversible reaction Lactate can increase from 1 mmol/kg (rest) to as high as 25 mmol/kg during intense exercise This can inhibit glycogen breakdown because: i) it impairs enzyme function in glycolysis and ii) decreases the muscles calcium-binding capacity, therefore impeding muscle-contraction 31  Lactic Acid vs Lactate Lactic acid and lactate are NOT the same compound. Lactic acid is an acid with the chemical formula C3H6O3 Lactate (C3H5O3) is any salt of lactic acid When lactic acid releases hydrogen ions (H)), the remaining compound joins with sodium ions (Na) or Potassium ions (K) to form a salt. Anaerobic glycolysis produces lactic acid, but it quickly dissociates, and the salt – lactate – is formed. For this reason, the terms often are used interchangeably. 32 33  Lactate Is Not a Waste Product Blood lactate potential uses: Lactate shuttle - Converted to pyruvate and oxidized as an energy source in another cell Gluconeogenesis - Converted back to glucose in the liver in Cori Cycle 34 35 36  Oxidative system (oxidative phosphorylation, aerobic metabolism) 37 Oxidative System w Relies on oxygen to breakdown fuels for energy w Produces ATP in mitochondria of cells w Can yield much more energy (ATP) than anaerobic systems  Is the primary method of energy production during endurance events 38 Oxidative Production of ATP 1. Aerobic glycolysis—cytoplasm 2. Krebs cycle—mitochondria 3. Electron transport chain—mitochondria 39 AEROBIC GLYCOLYSIS and the ETC Aerobic Glycolysis Pyruvate is irreversibly converted to acetyl CoA 40 Pyruvate to Acetyl CoA (3 carbons to 2 carbons) Each pyruvate loses a carbon, picks up oxygen and becomes carbon dioxide, which is released into the blood, circulated to the lungs, and breathed out. The 2-carbon compound picks up a molecule of CoA, becoming acetyl CoA 41 Oxaloacetate Kreb’s cycle Also called: - TCA cycle (tricarboxylic acid) - Citric acid cycle 42 Kreb’s Cycle Oxaloacetate, a compound made primarily from pyruvate, starts the Kreb’s cycle The 4-carbon oxaloacetate joins with the 2-carbon acetyl CoA The new 6-carbon compound releases carbons as CO2 becoming a 5-C and then a 4-C compound, etc until a series of reactions forms oxaloacetate again (and starts the cycle over)  Oxaloacetate Importantly, oxaloacetate cannot be made from fat. Oxaloacetate must be available for acetyl CoA to enter the Kreb’s cycle, therefore the importance of CHO in the diet. A diet that provides ample CHO ensures an adequate supply of oxaloacetate (because glucose produces pyruvate during glycolysis) One reason why a person (especially athletes) should not follow a low CHO diet. 44  Final Step in Aerobic Metabolism Electron Transport Chain (ETC) Gets hydrogen from NADH and FADH2 Occurs in the membrane of the mitochondria Generates a lot of ATP Results of ETC are: – Oxygen consumed – H2O and CO2 are produced – Energy captured in ATP Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH 2 to O 2 by a series of electron carriers. Simply, the oxidation of fuels and the phosphorylation of ADP is oxidative phosphorylation 45 Electron Transport Chain 46 OXIDATIVE PHOSPHORYLATION - ETC Within the mitochondria, ATP is formed at 3 sites along the ETC. This process is called oxidative phosphorylation. Overall ATP generated from CHO is 39 ATP. FAD – flavin adenine dinucleotide NAD – nicotinamide adenine dinucleotide 47 ¯ Video: oxidative phosphorylation http://www.youtube.com/watch?v=D68uKTG6H0o Professor Fink explains cellular respiration 48 Characteristics of the Energy Systems The energy yield differs for carbohydrate depending on whether NADH or FADH is the carrier molecule to transport the electron through the mitochondrial membrane 49  Energy Release From Fat Adipocytes (fat cells) Site of fat storage and mobilization Fat is stored primarily as triglycerides Mobilization First step in utilizing fatty acids is lipolysis (breakdown of fat) Triglycerides are split into fatty acids and glycerol The enzyme Hormone Sensitive Lipase (HSL) drives lipolysis 50  Transport and Uptake of Fatty Acids Fatty acids from lipolysis are FFA – Bound to Albumin (transport protein) for transport in plasma FFA are taken up by muscle cells – FFA are activated to fatty Acetyl CoA – Acetyl CoA binds to carnitine for transport into mitochondria – Carnitine Acyltransferase drives this reaction – (carnitine is made from lysine and helps transport FFA across the mitochondrial membrane) – Carnitine supposedly “burns” fat and spares glycogen during endurance events, but in reality it does neither !! 51 Fatty Acids from Lipoproteins Lipoproteins also transport triglycerides Lipoprotein Lipase (LPL) catalyzes hydrolysis of these triglycerides LPL is located on surface of surrounding capillaries and fat cells 52  Metabolism of Fat beta-oxidation (FA oxidation) - The breakdown of fatty acids to acetyl CoA NOTE: In beta-oxidation, the carbon chain of the FA is broken down into 2-Carbon segments Example: 16 carbon FA gives you 8 molecules of acetyl CoA from beta- oxidation - Two-carbon acetyl groups enter Kreb’s Cycle - Oxidation produces NADH only about 5% of fat (acetyl CoA) can be converted to glucose 53 METABOLISM OF FAT 54  Fats Enter the Energy Pathway Fat (triglycerides) Glucose phosphoglyceraldehyde Glycerol Fatty acids Pyruvate CoA CoA Carbon Coenzyme To Electron CoA Transport dioxide A Co A Chain Co Coenzyme A A Co CoA Co Acetyl CoA A Co Co CoA A To TCA Cycle 55 Energy Production From the Oxidation of a FA (Palmitic Acid (C16H32O2)) ATP produced from 1 molecule of palmitic acid By oxidative Stage of process Direct phosphorylation Fatty acid activation 0 –2 -oxidation 0 35 Krebs cycle 8 88 Subtotal 8 121 Total 129 56  Fats Burn in a Carbohydrate Flame Glycolytic production of pyruvate keeps required levels of oxaloacetate to maintain activity of beta oxidation Fatty acid degradation continues only if there is sufficient oxaloacetic acid (which combines with acetyl CoA) 57  Slower Rate of Energy Release From Fat Rate of fat oxidation is slower than that for carbohydrate Carbohydrate oxidation helps maintain fat oxidation rates Carbohydrate depletion impairs exercise performance 58 Protein Metabolism  Body uses very little protein during rest and exercise (less than 5% to 10%). Liver deamination of protein (removal of NH2 group) produces NH3 (ammonia) to form non-essential aa combines NH3 with CO2 to make urea (less toxic) Kidneys excretes excess urea, to remove nitrogen 59  Deamination of an Amino Acid The deamination of an amino acid produces ammonia (NH3) and a keto acid. Side Side group group Amino acid Keto acid 60  Urea Synthesis Ammonia Ammonia Carbon dioxide Water Urea 61  Amino Acids Enter the Energy Pathway Amino acids Most amino acids can be used to synthesize glucose; Pyruvate they are glucogenic. CoA Coenzyme Coenzyme To Electron Transport Chain Carbon dioxide Some amino acids are converted directly CoA to acetyl CoA; they are Acetyl CoA ketogenic. Some amino acids can enter the TCA To TCA Cycle cycle directly; they are glucogenic. 62  Metabolism of Carbohydrate, Fat, Protein The metabolism of carbohydrate, fat, and (to a lesser extent) protein shares some common pathways within the muscle fiber. The ATP generated by oxidative and nonoxidative metabolism are used by those steps in muscle contraction and relaxation that demand energy. 63 INTERACTION OF ENERGY SYSTEMS 64 Interaction of the Energy Systems 65  Oxidative Capacity of Muscle. Oxidative capacity of muscle (QO2) is a measure of its maximal capacity to use oxygen Representative enzymes to measure oxidative capacity in the muscle: – Succinate dehydrogenase – Citrate synthase 66  Oxidative Capacity in Muscle The relationship between muscle succinate dehydrogenase (SDH) activity and its oxidative capacity Measured in a biopsy sample taken from the vastus lateralis Endurance athletes’ muscles have nearly 2 – 4 times more oxidative enzymes than untrained men and women! 67 What Determines Oxidative Capacity? w Oxidative enzyme activity within the muscle w Fiber-type composition and number of mitochondria w Endurance training w Oxygen availability and uptake in the lungs 68  Luis is a long jumper on his College track team. His strength seems to be his sprint speed, but he has struggled occasionally with getting a powerful take-off from the board leading into the jump. Last season, his coach started incorporating plyometrics into his training program, and Luis seems to have improved his ability to achieve height and length in the jump. The combination of his sprinting speed and powerful jumping abilities has made Luis a solid long jumper. Answer the questions on the next slide…. 69 1. Luis’ body likely maintains his ATP levels via the ____________ system. a) Glycolytic b) ATP-PCr c) aerobic 2. The system that is maintaining Luis’ ATP levels produces ATP without the aid of __________________. a) Glycogen b) oxygen c) creatine 3. This system also uses the molecule PCr to rebuild ATP and maintain a relatively constant supply. The ___________________ enzyme acts on PCr to separate Pi from creatine. The energy released can then be used to couple Pi to an ADP molecule, forming ATP. a) Oxidative b) creatine kinase c) ATPase d) myokinase 4. Suppose that next season Luis switches to the 800-metre race, an event that average College athletes run in a little over 2 minutes. Think about Luis’ prior training and his energy systems. Initially, he will find his prior training to be ______________________ for the event. a) Inadequate b) adequate c) more than adequate 5. The first few seconds of the 800-metre race will feel good to Luis, but he will find that the length of the event will strain his ___________________ system. a) ATP-PCr b) ATP-PCr and oxidative c) Glycolytic d) aerobic and oxidative 70