Bioenergetics

Objectives Discuss the functions of the cell membrane, nucleus, and mitochondria. Define the following terms: (1) endergonic reactions, (2) exergonic reactions, (3) coupled reactions, and (4) bioenergetics. Describe the role of enzymes as catalysts in cellular chemical reactions. List and discuss the nutrients that are used as fuels during exercise. Identify the high-energy phosphates.

Objectives Discuss the biochemical pathways involved in anaerobic ATP production. Discuss the aerobic production of ATP. Describe the general scheme used to regulate metabolic pathways involved in bioenergetics. Discuss the interaction between aerobic and anaerobic ATP production during exercise. Identify the enzymes that are considered rate limiting in glycolysis and the Krebs cycle.

Introduction Metabolism Sum of all chemical reactions that occur in the body Anabolic reactions Synthesis of molecules Catabolic reactions Breakdown of molecules Bioenergetics Converting foodstuffs (fats, proteins, carbohydrates) into energy

Cell Structure Cell membrane Semipermeable membrane that separates the cell from the extracellular environment Nucleus Contains genes that regulate protein synthesis Molecular biology Cytoplasm Fluid portion of cell Contains organelles Mitochondria

A Typical Cell and Its Major Organelles Cell Structure A Typical Cell and Its Major Organelles Figure 3.1

Cell Structure In Summary Metabolism is defined as the total of all cellular reactions that occur in the body; this includes both the synthesis of molecules and the breakdown of molecules. Cell structure includes the following three major parts: (1) cell membrane, (2) nucleus, and (3) cytoplasm (called sarcoplasm in muscle). The cell membrane provides a protective barrier between the interior of the cell and the extracellular fluid. Genes (located within the nucleus) regulate protein synthesis within the cell. The cytoplasm is the fluid portion of the cell and contains numerous organelles

A Closer Look 3.1 Molecular Biology and Exercise Science Cell Structure A Closer Look 3.1 Molecular Biology and Exercise Science Study of molecular structures and events underlying biological processes Relationship between genes and cellular characteristics they control Genes code for specific cellular proteins Process of protein synthesis Exercise training results in modifications in protein synthesis Strength training results in increased synthesis of muscle contractile protein Molecular biology provides “tools” for understanding the cellular response to exercise

Steps Leading to Protein Synthesis Biological Energy Transformation Steps Leading to Protein Synthesis DNA contains information to produce proteins. Transcription produces mRNA. mRNA leaves nucleus and binds to ribosome. Amino acids are carried to the ribosome by tRNA. In translation, mRNA is used to determine the arrangement of amino acids in the polypeptide chain. Figure 3.2

Cellular Chemical Reactions Biological Energy Transformation Cellular Chemical Reactions Endergonic reactions Require energy to be added Endothermic Exergonic reactions Release energy Exothermic Coupled reactions Liberation of energy in an exergonic reaction drives an endergonic reaction

The Breakdown of Glucose: An Exergonic Reaction Biological Energy Transformation The Breakdown of Glucose: An Exergonic Reaction Figure 3.3

Coupled Reactions Biological Energy Transformation The energy given off by the exergonic reaction powers the endergonic reaction Figure 3.4

Oxidation-Reduction Reactions Biological Energy Transformation Oxidation-Reduction Reactions Oxidation Removing an electron Reduction Addition of an electron Oxidation and reduction are always coupled reactions Often involves the transfer of hydrogen atoms rather than free electrons Hydrogen atom contains one electron A molecule that loses a hydrogen also loses an electron and therefore is oxidized Importance of NAD and FAD Creating ATP

Oxidation-Reduction Reaction Involving NAD and NADH Biological Energy Transformation Oxidation-Reduction Reaction Involving NAD and NADH Figure 3.5

Enzymes Catalysts that regulate the speed of reactions Biological Energy Transformation Enzymes Catalysts that regulate the speed of reactions Lower the energy of activation Factors that regulate enzyme activity Temperature pH Interact with specific substrates Lock and key model

Enzymes Catalyze Reactions Biological Energy Transformation Enzymes Catalyze Reactions Enzymes lower the energy of activation Figure 3.6

The Lock-and-Key Model of Enzyme Action Biological Energy Transformation The Lock-and-Key Model of Enzyme Action Substrate (sucrose) approaches the active site on the enzyme. Substrate fits into the active site, forming enzyme-substrate complex. The enzyme releases the products (glucose and fructose). Figure 3.7

Damaged cells release enzymes into the blood Biological Energy Transformation Clinical Applications 3.1 Diagnostic Value of Measuring Enzyme Activity in the Blood Damaged cells release enzymes into the blood Enzyme levels in blood indicate disease or tissue damage Diagnostic application Elevated lactate dehydogenase or creatine kinase in the blood may indicate a myocardial infarction

Examples of the Diagnostic Value of Enzymes in Blood Biological Energy Transformation Examples of the Diagnostic Value of Enzymes in Blood

Classification of Enzymes Biological Energy Transformation Classification of Enzymes Oxidoreductases Catalyze oxidation-reduction reactions Transferases Transfer elements of one molecule to another Hydrolases Cleave bonds by adding water Lyases Groups of elements are removed to form a double bond or added to a double bond Isomerases Rearrangement of the structure of molecules Ligases Catalyze bond formation between substrate molecules

Example of the Major Classes of Enzymes Biological Energy Transformation Example of the Major Classes of Enzymes

Factors That Alter Enzyme Activity Biological Energy Transformation Factors That Alter Enzyme Activity Temperature Small rise in body temperature increases enzyme activity Exercise results in increased body temperature pH Changes in pH reduces enzyme activity Lactic acid produced during exercise

The Effect of Body Temperature on Enzyme Activity Biological Energy Transformation The Effect of Body Temperature on Enzyme Activity Figure 3.8

The Effect of pH on Enzyme Activity Biological Energy Transformation The Effect of pH on Enzyme Activity Figure 3.9

Carbohydrates Glucose Glycogen Blood sugar Fuels for Exercise Carbohydrates Glucose Blood sugar Glycogen Storage form of glucose in liver and muscle Synthesized by enzyme glycogen synthase Glycogenolysis Breakdown of glycogen to glucose

Fats Fatty acids Primary type of fat used by the muscle Triglycerides Fuels for Exercise Fats Fatty acids Primary type of fat used by the muscle Triglycerides Storage form of fat in muscle and adipose tissue Breaks down into glycerol and fatty acids Phospholipids Not used as an energy source Steroids Derived from cholesterol Needed to synthesize sex hormones

Protein Composed of amino acids Fuels for Exercise Protein Composed of amino acids Some can be converted to glucose in the liver Gluconeogenesis Others can be converted to metabolic intermediates Contribute as a fuel in muscle Overall, protein is not a primary energy source during exercise

Fuels for Exercise In Summary The body uses carbohydrate, fat, and protein nutrients consumed daily to provide the necessary energy to maintain cellular activities both at rest and during exercise. During exercise, the primary nutrients used for energy are fats and carbohydrates, with protein contributing a relatively small amount of the total energy used. Glucose is stored in animal cells as a polysaccharide called glycogen. Fatty acids are the primary form of fat used as an energy source in cells. Fatty acids are stored as triglycerides in muscle and fat cells.

High-Energy Phosphates Adenosine triphosphate (ATP) Consists of adenine, ribose, and three linked phosphates Synthesis Breakdown ADP + Pi  ATP ADP + Pi + Energy ATP ATPase

High-Energy Phosphates Structure of ATP Figure 3.10

Model of ATP as the Universal Energy Donor High-Energy Phosphates Model of ATP as the Universal Energy Donor Figure 3.11

Bioenergetics Formation of ATP Phosphocreatine (PC) breakdown Degradation of glucose and glycogen Glycolysis Oxidative formation of ATP Anaerobic pathways Do not involve O2 PC breakdown and glycolysis Aerobic pathways Require O2 Oxidative phosphorylation

Anaerobic ATP Production Bioenergetics Anaerobic ATP Production ATP-PC system Immediate source of ATP Glycolysis Glucose  2 pyruvic acid or 2 lactic acid Energy investment phase Requires 2 ATP Energy generation phase Produces 4 ATP, 2 NADH, and 2 pyruvate or 2 lactate ATP + C PC + ADP Creatine kinase

Bioenergetics The Winning Edge 3.1 Does Creatine Supplementation Improve Exercise Performance? Depletion of PC may limit short-term, high-intensity exercise Creatine monohydrate supplementation Increased muscle PC stores Some studies show improved performance in short-term, high-intensity exercise Inconsistent results may be due to water retention and weight gain Increased strength and fat-free mass with resistance training Creatine supplementation does not appear to pose health risks

A Closer Look 3.2 Lactic Acid or Lactate? Bioenergetics A Closer Look 3.2 Lactic Acid or Lactate? Terms lactic acid and lactate used interchangeably Lactate is the conjugate base of lactic acid Lactic acid is produced in glycolysis Rapidly disassociates to lactate and H+ The ionization of lactic acid forms the conjugate base called lactate Figure 3.12

The Two Phases of Glycolysis Bioenergetics The Two Phases of Glycolysis Figure 3.13

Interaction Between Blood Glucose and Muscle Glycogen in Glycolysis Bioenergetics Interaction Between Blood Glucose and Muscle Glycogen in Glycolysis Figure 3.14

Glycolysis: Energy Investment Phase Bioenergetics Glycolysis: Energy Investment Phase Figure 3.15

Glycolysis: Energy Generation Phase Bioenergetics Figure 3.15

Hydrogen and Electron Carrier Molecules Bioenergetics Hydrogen and Electron Carrier Molecules Transport hydrogens and associated electrons To mitochondria for ATP generation (aerobic) To convert pyruvic acid to lactic acid (anaerobic) Nicotinamide adenine dinucleotide (NAD) Flavin adenine dinucleotide (FAD) NAD + 2H+  NADH + H+ FAD + 2H+  FADH2

NADH is “Shuttled” into Mitochondria Bioenergetics NADH is “Shuttled” into Mitochondria NADH produced in glycolysis must be converted back to NAD By converting pyruvic acid to lactic acid By “shuttling” H+ into the mitochondria A specific transport system shuttles H+ across the mitochondrial membrane Located in the mitochondrial membrane

Conversion of Pyruvic Acid to Lactic Acid Bioenergetics The addition of two H+ to pyruvic acid forms NAD and lactic acid Figure 3.16

In Summary ADP + Pi + Energy ATP Bioenergetics In Summary The immediate source of energy for muscular contraction is the high-energy phosphate ATP. ATP is degraded via the enzyme ATPase as follows: Formation of ATP without the use of O2 is termed anaerobic metabolism. In contrast, the production of ATP using O2 as the final electron acceptor is referred to as aerobic metabolism. ADP + Pi + Energy ATP ATPase

Bioenergetics In Summary Exercising skeletal muscles produce lactic acid. However, once produced in the body, lactic acid is rapidly converted to its conjugate base, lactate. Muscle cells can produce ATP by any one or a combination of three metabolic pathways: (1) ATP-PC system, (2) glycolysis, (3) oxidative ATP production. The ATP-PC system and glycolysis are two anaerobic metabolic pathways that are capable of producing ATP without O2.

Aerobic ATP Production Bioenergetics Aerobic ATP Production Krebs cycle (citric acid cycle) Pyruvic acid (3 C) is converted to acetyl-CoA (2 C) CO2 is given off Acetyl-CoA combines with oxaloacetate (4 C) to form citrate (6 C) Citrate is metabolized to oxaloacetate Two CO2 molecules given off Produces three molecules of NADH and one FADH Also forms one molecule of GTP Produces one ATP

The Three Stages of Oxidative Phosphorylation Bioenergetics The Three Stages of Oxidative Phosphorylation Figure 3.17

Bioenergetics The Krebs Cycle Figure 3.18

Fats and Proteins in Aerobic Metabolism Bioenergetics Fats and Proteins in Aerobic Metabolism Fats Triglycerides  glycerol and fatty acids Fatty acids  acetyl-CoA Beta-oxidation Glycerol is not an important muscle fuel during exercise Protein Broken down into amino acids Converted to glucose, pyruvic acid, acetyl-CoA, and Krebs cycle intermediates

Bioenergetics Relationship Between the Metabolism of Proteins, Carbohydrates, and Fats Figure 3.19

Aerobic ATP Production Bioenergetics Aerobic ATP Production Electron transport chain Oxidative phosphorylation occurs in the mitochondria Electrons removed from NADH and FADH are passed along a series of carriers (cytochromes) to produce ATP Each NADH produces 2.5 ATP Each FADH produces 1.5 ATP Called the chemiosmotic hypothesis H+ from NADH and FADH are accepted by O2 to form water

The Chemiosmotic Hypothesis of ATP Formation Bioenergetics The Chemiosmotic Hypothesis of ATP Formation Electron transport chain results in pumping of H+ ions across inner mitochondrial membrane Results in H+ gradient across membrane Energy released to form ATP as H+ ions diffuse back across the membrane

The Electron Transport Chain Bioenergetics The Electron Transport Chain Figure 3.20

Beta Oxidation is the Process of Converting Fatty Acids to Acetyl-CoA Bioenergetics Beta Oxidation is the Process of Converting Fatty Acids to Acetyl-CoA Breakdown of triglycerides releases fatty acids Fatty acids must be converted to acetyl-CoA to be used as a fuel Activated fatty acid (fatty acyl-CoA) into mitochondrion Fatty acid “chopped” into 2 carbon fragments forming acetyl-CoA Acetyl-CoA enters Krebs cycle and is used for energy

Bioenergetics Beta Oxidation Figure 3.21

Bioenergetics In Summary Oxidative phosphorylation or aerobic ATP production occurs in the mitochondria as a result of a complex interaction between the Krebs cycle and the electron transport chain. The primary role of the Krebs cycle is to complete the oxidation of substrates and form NADH and FADH to enter the electron transport chain. The end result of the electron transport chain is the formation of ATP and water. Water is formed by oxygen-accepting electrons; hence, the reason we breathe oxygen is to use it as the final acceptor of electrons in aerobic metabolism.

A Closer Look 3.5 A New Look at the ATP Balance Sheet Aerobic ATP Tally A Closer Look 3.5 A New Look at the ATP Balance Sheet Historically, 1 glucose produced 38 ATP Recent research indicates that 1 glucose produces 32 ATP Energy provided by NADH and FADH also used to transport ATP out of mitochondria. 3 H+ must pass through H+ channels to produce 1 ATP Another H+ needed to move the ATP across the mitochondrial membrane

Aerobic ATP Tally Per Glucose Molecule

Efficiency of Oxidative Phosphorylation One mole of ATP has energy yield of 7.3 kcal 32 moles of ATP are formed from one mole of glucose Potential energy released from one mole of glucose is 686 kcal/mole Overall efficiency of aerobic respiration is 34% 66% of energy released as heat 32 moles ATP/mole glucose x 7.3 kcal/mole ATP 686 kcal/mole glucose x 100 = 34%

Efficiency of Oxidative Phosphorylation In Summary The aerobic metabolism of one molecule of glucose results in the production of 32 ATP molecules, whereas the aerobic yield for glycogen breakdown is 33 ATP. The overall efficiency of aerobic of aerobic respiration is approximately 34%, with the remaining 66% of energy being released as heat.

Control of Bioenergetics Rate-limiting enzymes An enzyme that regulates the rate of a metabolic pathway Modulators of rate-limiting enzymes Levels of ATP and ADP+Pi High levels of ATP inhibit ATP production Low levels of ATP and high levels of ADP+Pi stimulate ATP production Calcium may stimulate aerobic ATP production

Example of a Rate-Limiting Enzyme Control of Bioenergetics Example of a Rate-Limiting Enzyme Figure 3.22

Factors Known to Affect Rate-Limiting Enzymes Control of Bioenergetics Factors Known to Affect Rate-Limiting Enzymes

Control of Bioenergetics In Summary Metabolism is regulated by enzymatic activity. An enzyme that regulates a metabolic pathway is termed a “rate-limiting” enzyme. The rate-limiting enzyme for glycolysis is phosphofructokinase, while the rate-limiting enzymes for the Krebs cycle and electron transport chain are isocitrate dehydrogenase and cytochrome oxidase, respectively. In general, cellular levels of ATP and ADP+Pi regulate the rate of metabolic pathways involved in the production of ATP. High levels of ATP inhibit further ATP production, while low levels of ATP and high levels of ADP+Pi stimulate ATP production. Evidence also exists that calcium may stimulate aerobic energy metabolism.

Interaction Between Aerobic/Anaerobic ATP Production Energy to perform exercise comes from an interaction between aerobic and anaerobic pathways Effect of duration and intensity Short-term, high-intensity activities Greater contribution of anaerobic energy systems Long-term, low to moderate-intensity exercise Majority of ATP produced from aerobic sources

Interaction Between Aerobic/Anaerobic ATP Production Contribution of Aerobic/Anaerobic ATP Production During Sporting Events Figure 3.23

Interaction Between Aerobic/Anaerobic ATP Production In Summary Energy to perform exercise comes from an interaction of anaerobic and aerobic pathways. In general, the shorter the activity (high intensity), the greater the contribution of anaerobic energy production. In contrast, long-term activities (low to moderate intensity) utilize ATP produced from aerobic sources.