Fuel for Exercise: Bioenergetics and Muscle Metabolism Chapter 2 Fuel for Exercise: Bioenergetics and Muscle Metabolism

Chapter 2 Overview Substrates: fuel for exercise Controlling the rate of energy production Stored energy: high-energy phosphates Bioenergetics: basic energy systems Interaction among energy systems

Terminology Substrates Bioenergetics Fuel sources from which we make energy (adenosine triphosphate [ATP]) Carbohydrate, fat, protein Bioenergetics Process of converting substrates into energy Performed at cellular level Metabolism: chemical reactions in the body

Measuring Energy Release Can be calculated from heat produced 1 calorie (cal) = heat energy required to raise 1 g of water from 14.5°C to 15.5°C 1,000 cal = 1 kcal = 1 Calorie (dietary)

Substrates: Fuel for Exercise Carbohydrate, fat, protein Carbon, hydrogen, oxygen, nitrogen Energy from chemical bonds in food stored in high-energy compound ATP Resting: 50% carbohydrate, 50% fat Exercise (short): more carbohydrate Exercise (long): carbohydrate, fat

Carbohydrate All carbohydrate converted to glucose 4.1 kcal/g; ~2,500 kcal stored in body Primary ATP substrate for muscles, brain Extra glucose stored as glycogen in liver, muscles Glycogen converted back to glucose when needed to make more ATP Glycogen stores limited (2,500 kcal), must rely on dietary carbohydrate to replenish

Fat Efficient substrate, efficient storage 9.4 kcal/g +70,000 kcal stored in body Energy substrate for prolonged, less intense exercise High net ATP yield but slow ATP production Must be broken down into free fatty acids (FFAs) and glycerol Only FFAs are used to make ATP

Table 2.1

Protein Energy substrate during starvation 4.1 kcal/g Must be converted into glucose (gluconeogenesis) Can also convert into FFAs (lipogenesis) For energy storage For cellular energy substrate

Figure 2.1

Controlling Rate of Energy Production by Substrate Availability Energy released at a controlled rate based on availability of primary substrate Mass action effect Substrate availability affects metabolic rate More available substrate = higher pathway activity Excess of given substrate = cells rely on that energy substrate more than others

Controlling Rate of Energy Production by Enzyme Activity Energy released at a controlled rate based on enzyme activity in metabolic pathway Enzymes Do not start chemical reactions or set ATP yield Do facilitate breakdown (catabolism) of substrates Lower the activation energy for a chemical reaction End with suffix -ase ATP broken down by ATPase

Figure 2.2

Controlling Rate of Energy Production by Enzyme Activity Each step in a biochemical pathway requires specific enzyme(s) More enzyme activity = more product Rate-limiting enzyme Can create bottleneck at an early step Activity influenced by negative feedback Slows overall reaction, prevents runaway reaction

Figure 2.3

Stored Energy: High-Energy Phosphates ATP stored in small amounts until needed Breakdown of ATP to release energy ATP + water + ATPase  ADP + Pi + energy ADP: lower-energy compound, less useful Synthesis of ATP from by-products ADP + Pi + energy  ATP (via phosphorylation) Can occur in absence or presence of O2

Figure 2.4

Bioenergetics: Basic Energy Systems ATP storage limited Body must constantly synthesize new ATP Three ATP synthesis pathways ATP-PCr system (anaerobic metabolism) Glycolytic system (anaerobic metabolism) Oxidative system (aerobic metabolism)

ATP-PCr System Anaerobic, substrate-level metabolism ATP yield: 1 mol ATP/1 mol PCr Duration: 3 to 15 s Because ATP stores are very limited, this pathway is used to reassemble ATP

ATP-PCr System Phosphocreatine (PCr): ATP recycling PCr + creatine kinase  Cr + Pi + energy PCr energy cannot be used for cellular work PCr energy can be used to reassemble ATP Replenishes ATP stores during rest Recycles ATP during exercise until used up (~3-15 s maximal exercise)

Figure 2.5

Figure 2.6

Control of ATP-PCr System: Creatine Kinase (CK) PCr breakdown catalyzed by CK CK controls rate of ATP production Negative feedback system When ATP levels  (ADP ), CK activity  When ATP levels , CK activity 

Glycolytic System Anaerobic ATP yield: 2 to 3 mol ATP/1 mol substrate Duration: 15 s to 2 min Breakdown of glucose via glycolysis

Glycolytic System Uses glucose or glycogen as its substrate Must convert to glucose-6-phosphate Costs 1 ATP for glucose, 0 ATP for glycogen Pathway starts with glucose-6-phosphate, ends with pyruvic acid 10 to 12 enzymatic reactions total All steps occur in cytoplasm ATP yield: 2 ATP for glucose, 3 ATP for glycogen

Glycolytic System Cons Pros Low ATP yield, inefficient use of substrate Lack of O2 converts pyruvic acid to lactic acid Lactic acid impairs glycolysis, muscle contraction Pros Allows muscles to contract when O2 limited Permits shorter-term, higher-intensity exercise than oxidative metabolism can sustain

Glycolytic System Phosphofructokinase (PFK) Rate-limiting enzyme  ATP ( ADP)   PFK activity  ATP   PFK activity Also regulated by products of Krebs cycle Glycolysis = ~2 min maximal exercise Need another pathway for longer durations

Oxidative System Aerobic ATP yield: depends on substrate 32 to 33 ATP/1 glucose 100+ ATP/1 FFA Duration: steady supply for hours Most complex of three bioenergetic systems Occurs in the mitochondria, not cytoplasm

Oxidation of Carbohydrate Stage 1: Glycolysis Stage 2: Krebs cycle Stage 3: Electron transport chain

Figure 2.8

Oxidation of Carbohydrate: Glycolysis Revisited Glycolysis can occur with or without O2 ATP yield same as anaerobic glycolysis Same general steps as anaerobic glycolysis but, in the presence of oxygen, Pyruvic acid  acetyl-CoA, enters Krebs cycle

Oxidation of Carbohydrate: Krebs Cycle 1 Molecule glucose  2 acetyl-CoA 1 molecule glucose  2 complete Krebs cycles 1 molecule glucose  double ATP yield 2 Acetyl-CoA  2 GTP  2 ATP Also produces NADH, FADH, H+ Too many H+ in the cell = too acidic H+ moved to electron transport chain

Figure 2.9

Oxidation of Carbohydrate: Electron Transport Chain H+, electrons carried to electron transport chain via NADH, FADH molecules H+, electrons travel down the chain H+ combines with O2 (neutralized, forms H2O) Electrons + O2 help form ATP 2.5 ATP per NADH 1.5 ATP per FADH

Oxidation of Carbohydrate: Energy Yield 1 glucose = 32 ATP 1 glycogen = 33 ATP Breakdown of net totals Glycolysis = +2 (or +3) ATP GTP from Krebs cycle = +2 ATP 10 NADH = +25 ATP 2 FADH = +3 ATP

Figure 2.10

Figure 2.11

Oxidation of Fat Triglycerides: major fat energy source Broken down to 1 glycerol + 3 FFAs Lipolysis, carried out by lipases Rate of FFA entry into muscle depends on concentration gradient Yields ~3 to 4 times more ATP than glucose Slower than glucose oxidation

b-Oxidation of Fat Process of converting FFAs to acetyl-CoA before entering Krebs cycle Requires up-front expenditure of 2 ATP Number of steps depends on number of carbons on FFA 16-carbon FFA yields 8 acetyl-CoA Compare: 1 glucose yields 2 acetyl-CoA Fat oxidation requires more O2 now, yields far more ATP later

Oxidation of Fat: Krebs Cycle, Electron Transport Chain Acetyl-CoA enters Krebs cycle From there, same path as glucose oxidation Different FFAs have different number of carbons Will yield different number of acetyl-CoA molecules ATP yield will be different for different FFAs Example: for palmitic acid (16 C): 129 ATP net yield

Table 2.2

Oxidation of Protein Rarely used as a substrate Starvation Can be converted to glucose (gluconeogenesis) Can be converted to acetyl-CoA Energy yield not easy to determine Nitrogen presence unique Nitrogen excretion requires ATP expenditure Generally minimal, estimates therefore ignore protein metabolism

Control of Oxidative Phosphorylation: Negative Feedback Negative feedback regulates Krebs cycle Isocitrate dehydrogenase: rate-limiting enzyme Similar to PFK for glycolysis Regulates electron transport chain Inhibited by ATP, activated by ADP

Figure 2.12

Interaction Among Energy Systems All three systems interact for all activities No one system contributes 100%, but One system often dominates for a given task More cooperation during transition periods

Figure 2.13

Table 2.3

Oxidative Capacity of Muscle Not all muscles exhibit maximal oxidative capabilities Factors that determine oxidative capacity Enzyme activity Fiber type composition, endurance training O2 availability versus O2 need

Enzyme Activity Not all muscles exhibit optimal activity of oxidative enzymes Enzyme activity predicts oxidative potential Representative enzymes Succinate dehydrogenase Citrate synthase Endurance trained versus untrained

Figure 2.14

Fiber Type Composition and Endurance Training Type I fibers: greater oxidative capacity More mitochondria High oxidative enzyme concentrations Type II better for glycolytic energy production Endurance training Enhances oxidative capacity of type II fibers Develops more (and larger) mitochondria More oxidative enzymes per mitochondrion

Oxygen Needs of Muscle As intensity , so does ATP demand In response Rate of oxidative ATP production  O2 intake at lungs  O2 delivery by heart, vessels  O2 storage limited—use it or lose it O2 levels entering and leaving the lungs accurate estimate of O2 use in muscle