Fuel for Exercise:Bioenergetics and Muscle Metabolism

CHAPTER 2 CHAPTER 2 OverviewOverview

• Substrates: fuel for exercise

• Controlling the rate of energy production

• Stored energy: high-energy phosphates

• Bioenergetics: basic energy systems

• Interaction among energy systems

TerminologyTerminology

• Substrates– 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 ReleaseMeasuring 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 ExerciseSubstrates: 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

CarbohydrateCarbohydrate

• 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

FatFat

• 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 2.1Table 2.1

ProteinProtein

• 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 2.1Figure 2.1

Controlling Rate of Energy Production Controlling Rate of Energy Production by Substrate Availabilityby 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 Controlling Rate of Energy Production by Enzyme Activityby 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 2.2Figure 2.2

Controlling Rate of Energy Production Controlling Rate of Energy Production by Enzyme Activityby 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 2.3Figure 2.3

Stored Energy: Stored Energy: High-Energy PhosphatesHigh-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 2.4Figure 2.4

Bioenergetics: Basic Energy SystemsBioenergetics: 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 SystemATP-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 SystemATP-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 2.5Figure 2.5

Figure 2.6Figure 2.6

Control of ATP-PCr System:Control of ATP-PCr System:Creatine Kinase (CK)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 SystemGlycolytic System

• Anaerobic

• ATP yield: 2 to 3 mol ATP/1 mol substrate

• Duration: 15 s to 2 min

• Breakdown of glucose via glycolysis

Glycolytic SystemGlycolytic 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 SystemGlycolytic System

• Cons– 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 SystemGlycolytic 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 SystemOxidative 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 CarbohydrateOxidation of Carbohydrate

• Stage 1: Glycolysis

• Stage 2: Krebs cycle

• Stage 3: Electron transport chain

Figure 2.8Figure 2.8

Oxidation of Carbohydrate:Oxidation of Carbohydrate:Glycolysis RevisitedGlycolysis 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:Oxidation of Carbohydrate:Krebs CycleKrebs 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 2.9Figure 2.9

Oxidation of Carbohydrate:Oxidation of Carbohydrate:Electron Transport ChainElectron 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:Oxidation of Carbohydrate:Energy YieldEnergy 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 2.10Figure 2.10

Figure 2.11Figure 2.11

Oxidation of FatOxidation 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

-Oxidation of Fat-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:Oxidation of Fat:Krebs Cycle, Electron Transport ChainKrebs 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 2.2Table 2.2

Oxidation of ProteinOxidation 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:Control of Oxidative Phosphorylation:Negative FeedbackNegative 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 2.12Figure 2.12

Interaction Among Energy SystemsInteraction 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 2.13Figure 2.13

Table 2.3Table 2.3

Oxidative Capacity of MuscleOxidative 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 ActivityEnzyme 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 2.14Figure 2.14

Fiber Type Composition Fiber Type Composition and Endurance Trainingand 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 MuscleOxygen 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