chapter 2 Fuel for Exercising Muscle: Metabolism and Hormonal Control

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 the three metabolic systems that generate ATP Learn how the endocrine system monitors and responds to changes in the body’s systems during exercise

Metabolism and Bioenergetics Nutrients from foods are the substrates for metabolism and are provided and stored as: Carbohydrate Fat Protein Each cell contains chemical pathways that convert these substrates to usable energy, a process called bioenergetics The energy we derive from food is stored in cells in the form of adenosine triphosphase (ATP) ATP serves as the immediate source of energy for most body functions including muscle contraction

Kilocalorie Energy in biological systems is measured in kilocalories All energy eventually degrades to heat One kilocalorie is the amount of heat energy needed to raise 1 kg of water from 1 °C to 15 °C

Energy Sources At rest, the body uses carbohydrate and fat almost equally for energy Protein provides little energy for cellular activity, but serves as the building blocks for the body’s tissues During intense short-duration muscular effort, the body relies mostly on carbohydrate to generate ATP Longer, less intense exercise utilizes carbohydrates and fat for sustained energy production

Carbohydrate All dietary carbohydrate is ultimately converted to glucose Glucose is taken up by muscles and liver and converted to the complex sugar molecule called glycogen Glycogen is stored in the cytoplasm of muscle cells, where it can be quickly used to form ATP Glycogen is also stored in the liver, where it is converted back to glucose as needed and transported by the blood to the muscles to form ATP

Fat Provides substantial energy during prolonged, low-intensity activity Body stores of fat are larger than carbohydrate reserves Fat is less readily available for cellular metabolism compared to carbohydrate Fat is stored as triglycerides and must be broken down to free fatty acids (FFAs) to be used in metabolism More energy is derived from breaking down fat (9.4 kcal/g) compared to carbohydrate (4.1 kcal/g)

Protein Protein can be used as a minor source of energy, but it must be converted to glucose via glucogenesis Proteins can generate FFAs during starvation through lipogenesis Protein can supply up to 5-10% of energy during prolonged exercise Proteins must be broken down to their basic units—amino acids—to be used for energy

The Lock-and-Key Action of Enzymes in the Catabolism of Compounds Enzymes control the rate of free energy release from substrates Enzyme names end with the suffix -ase

Energy for Cellular Metabolism Key Points We derive energy from food and store it as the high- energy compound ATP Carbohydrate (4.1 kcal/g) Fat (9.4 kcal/g) Protein (4.1 kcal/g) Carbohydrate is stored as glycogen in muscles and the liver and is more accessible than protein or fat Glucose, directly from food or broken down from glycogen, is the usable form of carbohydrate Fat is stored as triglycerides in adipose tissue and broken down to FFA

ATP Is Generated Through 3 Energy Systems ATP-PCr system Glycolytic system Oxidative system

ATP Is Generated Through 3 Energy Systems

ATP-PCr System Cells store small amounts of ATP, and phosphocreatine (PCr), which is broken down to regenerate ATP Release of ATP from PCr is facilitated by the enzyme creatine kinase This process does not require oxygen (anaerobic) ATP and PCr sustain the muscle’s energy needs for 3-15 sec during an all-out sprint 1 mole of ATP is produced per one mole of PCr

ATP-Phosphocreatine System

ATP-PCr Although ATP is being used at a very high rate, the energy from PCr is used to resynthesize ATP, preventing the ATP level from decreasing. At exhaustion, both ATP and PCr concentrations are low.

Glycogen Breakdown and Synthesis Glycolysis is the breakdown of glucose; it may be anaerobic or aerobic. Glycogenesis is the process by which glycogen is synthesized from glucose to be stored in the liver or muscle. Glycogenolysis is the process by which glycogen is broken down into glucose-1-phosphate to be used for energy production.

The Glycolytic System Requires 10-12 enzymatic reactions to break down glycogen to lactic acid, producing ATP Occurs in the cytoplasm Glycolysis does not require oxygen (anaerobic) Without oxygen present, pyruvic acid produced by glycolysis becomes lactic acid 1 mole of glycogen produces 3 moles of ATP; 1 mole of glucose produces 2 moles of ATP because 1 mole is used to convert glucose to glucose-6-phosphate ATP-PCr and glycolysis provide the energy for ~2 min of all-out activity

Glycolysis

ATP-PCr and Glycolytic Systems Key Points ATP-PCr system Pi is separated from PCr by creatine kinase Pi is combined with ADP to form ATP Energy yield: 1 mole of ATP per 1 mole of PCr Glycolytic system Glucose or glycogen is broken down to pyruvic acid Without oxygen, pyruvic acid is converted to lactic acid 1 mole of glucose yields 2 moles of ATP 1 mole of glycogen yields 3 moles of ATP

Energy Sources for the Early Minutes of Intense Exercise The combined actions of the ATP-PCr and glycolytic systems allow muscles to generate force in the absence of oxygen; thus these two energy systems are the major energy contributors during the early minutes of high-intensity exercise.

The Oxidative System The oxidative system uses oxygen to generate energy from metabolic fuels (aerobic) Oxidative production of ATP occurs in the mitochondria Can yield much more energy (ATP) than anaerobic systems The oxidative system is slow to turn on Primary method of energy production during endurance events

Aerobic Glycolysis and the Electron Transport Chain

Krebs Cycle

Oxidation of Carbohydrate In the presence of oxygen, pyruvic acid from glycolysis is converted to acetyl coenzyme A (acetyl CoA) Acetyl CoA enters the Krebs cycle and forms 2 ATP, carbon dioxide, and hydrogen Hydrogen ion created during glycolysis and through the Krebs cycle combines with two coenzymes (NAD and FAD) NAD and FAD carry hydrogen ions to the electron transport chain (NAD and FAD → NADH and FADH)

The Electron Transport Chain The electron transport chain splits NADH and FADH, producing hydrogen ions which are recombined with oxygen to produce water Electrons produced from the split of NADH and FADH provide the energy for the phosphorylation of ADP to ATP One molecule of glycogen can generate up to 37-39 molecules of ATP

Oxidative Phosphorylation: The Electron Transport Chain

Oxidation of Fat Lipolysis is the breakdown of triglycerides into glycerol and free fatty acids (FFAs) FFAs travel via blood to muscle fibers and are broken down by enzymes in the mitochondria into acetic acid, which is converted to acetyl CoA through β-oxidation Acetyl CoA enters the Krebs cycle and the electron transport chain Fat oxidation requires more oxygen compared with glucose because a FFA molecule contains more carbon

Oxidation of Protein Body uses little protein during rest and exercise (5-10% to sustain prolonged exercise) Some amino acids can be converted into glucose or intermediates of oxidative metabolism Energy yield from protein is difficult to determine The nitrogen in amino acids is converted into urea, which requires ATP

Common Pathways for the Metabolism of Fat, Carbohydrate, and Protein

Interaction of the Energy Systems

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 Succinate dehydrogenase Citrate synthase

Oxidative Capacity in Muscle

Oxidative Metabolism Key Points The oxidative system involves the breakdown of substrates in the presence of oxygen Oxidation of carbohydrate involves glycolysis, the Krebs cycle, and the electron transport chain, resulting in the formation of H2O, CO2, and 38-39 molecules of ATP Fat oxidation involves β-oxidation of free fatty acids, the Krebs cycle, and the electron transport chain to produce more ATP than carbohydrate The maximum rate of ATP formation from fat oxidation is too low to match the rate of ATP utilization during high intensity exercise (continued)

Oxidative Metabolism (continued) Key Points Protein contributes little to energy production, and its oxidation is complex because amino acids contain nitrogen, which cannot be oxidized The oxidative capacity of muscle fibers depends on their oxidative enzyme levels, fiber-type composition, and oxygen availability

Hormonal Control Hormones significantly affect metabolism Hormones are secreted directly into the blood and act as chemical signals to their target cells Hormones travel away from the cells that secrete them and specifically affect the activities of other cells and organs 2 types of hormones: steroid and nonsteroid Hormone secretion is regulated by negative feedback Hormone receptors can increase (upregulation) or decrease (downregulation)

Locations of the Major Endocrine Organs

Steroid Hormones Formed from cholesterol Lipid soluble Capable of direct gene activation Receptors are in the cytoplasm or in the nucleus mRNA activation promotes protein synthesis Examples Adrenal cortex (cortisol and aldosterone) Ovaries (estrogen and progesterone) Testes (testosterone) Placenta (estrogen and progesterone)

The Mechanism of Action of a Steroid Hormone

Nonsteroid Hormones Protein or peptide and amino acid-derived Not lipid soluble Triggers a series of intracellular events through second messenger systems, cAMP Activates cellular enzymes Changes membrane permeability Promotes protein synthesis Changes cellular metabolism Stimulates cellular secretions Examples Thyroid gland (thyroxine and triiodothyronine) Adrenal medulla (epinephrine and norepinephrine)

The Mechanism of Action of a Nonsteroid Hormone

Hormonal Control Key Points Hormones are secreted into the blood and then circulate to target cells where they bind to receptors on the target tissue Steroid hormones pass through the cell membrane to bind with receptors in the cell to directly activate genes causing protein synthesis Nonsteroid hormones bind to receptors in the cell membrane and activate second messenger systems which trigger numerous cellular processes (continued)

Hormonal Control (continued) Key Points A negative feedback system regulates secretion of most hormones The number of hormone receptors can be altered Upregulation—increase in the number of available receptors Downregulation—decrease in the number of available receptors

Regulation of Glucose Metabolism During Exercise Glucose concentration during exercise is a balance between glucose uptake by the exercising muscles and its release by the liver ↑ Glucagon: promotes liver glycogen breakdown and glucose formation from amino acids ↑ Epinephrine: promotes glycogenolysis ↑ Norephinephrine: promotes glycogenolysis ↑ Cortisol: promotes protein catabolism

Changes in Plasma Concentrations of Epinephrine, Norepinephrine, Glucagon, Cortisol and Glucose During 3 h of Cycling at 65% of VO2max .

Glucose Uptake by Muscle Plasma insulin concentrations decrease during prolonged submaximal exercise Exercise may enhance insulin’s binding to receptors on the muscle fiber, reducing the need for high concentrations of plasma insulin to transport glucose

Changes in Plasma Concentrations During Cycling at 65% to 70% of VO2max .

Regulation of Fat Metabolism During Exercise Lipolysis is hormonally controlled during exercise by: Decreased insulin Epinephrine Norepinephrine Cortisol Growth hormone

Hormonal Control of Metabolism During Exercise Key Points Plasma glucose is increased by the combined actions of glucagon, epinephrine, norepinephrine, and cortisol Insulin helps glucose enter the cell, but declines during prolonged exercise When carbohydrate reserves are low, the body turns to more fat oxidation, and lipolysis is increased, which is facilitated by decreased insulin and increased epinephrine, norepinephrine, cortisol, and growth hormone

Hormonal Regulation of Fluid and Electrolyte Balance During Exercise Fluid balance during exercise is critical for optimal metabolic, cardiovascular, and thermoregulatory function The endocrine system plays a major role in monitoring fluid levels and correcting imbalances Regulates electrolyte balance (especially Na+) Antidiuretic hormone (ADH) Aldosterone

Antidiuretic Hormone Released from the posterior pituitary Hemoconcentration during exercise, increased plasma osmolality, and low plasma volume stimulate the release of ADH ADH promotes water retention in the kidney in an effort to dilute plasma electrolyte concentrations back to normal

Mechanism by which ADH Conserves Body Water

Aldosterone Mineralcorticoid hormone Secretion is stimulated by: ↓ plasma sodium ↓ blood volume ↓ pressure ↑ plasma potassium concentration Promotes renal reabsorption of sodium, causing the body to retain sodium

Changes in Plasma Volume and Aldosterone Concentrations During Cycling

Kidneys The kidneys strongly influence the maintenance of plasma volume and blood pressure regulation through the release of renin Renin initiates the renin-angiotensin-aldosterone mechanism

Exercise and Renal Function in the Regulation of Plasma Volume

Changes in Plasma Volume During Three Days of Repeated Exercise and Dehydration

Hormone Regulation of Fluid and Electrolyte Balance During Exercise Key Points The two primary hormones involved in the regulation of fluid balance are ADH and aldosterone ADH is released from the posterior pituitary in response to increased plasma osmolality and low blood volume ADH acts on the kidney, promoting water conservation When plasma volume or blood pressure decreases, the kidneys release renin, which converts angiotensinogen to angiotensin I, which later becomes angiotensin II (continued)

Hormone Regulation of Fluid and Electrolyte Balance During Exercise (continued) Key Points Angiotensin II increases peripheral resistance, increasing blood pressure Angiotensin II triggers the release of aldosterone from the adrenal cortex, which promotes sodium reabsorption in the kidney