1. Copyright © 2006 Lippincott Williams & Wilkins. Fundamentals of Human Energy Transfer Chapter 5

2. Copyright © 2006 Lippincott Williams & Wilkins. Fundamental Definitions Bioenergetics studies diverse means for energy transfer for biologic work within living organisms. Aerobic and anaerobic breakdown of food nutrients provides energy source for synthesizing the chemical fuel for all biologic work.

3. Copyright © 2006 Lippincott Williams & Wilkins. Energy: The Capacity for Work

4. Copyright © 2006 Lippincott Williams & Wilkins. First Law of Thermodynamics Conservation of energy Dictates that the body does not produce, consume, or use up energy; rather, energy transforms from one form into another as physiologic systems undergo continual change.

5. Copyright © 2006 Lippincott Williams & Wilkins. Definition of Energy Potential Energy: stored, inactive; ability to do work even if it is not doing work at the time. Kinetic Energy: energy at work, active.

6. Copyright © 2006 Lippincott Williams & Wilkins. Potential Energy as –Energy of position (gravitational) –Mechanical potential energy (elastic deformation) –Bound energy within internal structure Releasing potential energy transforms into kinetic energy of motion.

7. Copyright © 2006 Lippincott Williams & Wilkins. Energy-Releasing and Energy-Conserving Processes Exergonic reactions –Chemical processes that release energy to its surroundings –Downhill processes Endergonic reactions –Chemical processes that store or absorb energy –Uphill processes

8. Copyright © 2006 Lippincott Williams & Wilkins. Coupled Reactions

9. Copyright © 2006 Lippincott Williams & Wilkins. Second Law of Thermodynamics Tendency to degrade potential energy to kinetic energy with lower capacity for work (i.e., increase entropy). Food and other chemicals represent excellent sources of potential energy, yet energy decreases as compounds decompose via normal oxidation. Example: flashlight battery.

10. Copyright © 2006 Lippincott Williams & Wilkins. Forms of Energy During energy conversions, a loss of potential energy from one source often produces increase in potential energy of another source.

11. Copyright © 2006 Lippincott Williams & Wilkins. Biologic Work in Humans 1.Performance of mechanical work 2.Chemical work in biosynthesis of macromolecules 3.Active transport of molecules and ions concentrating various substances in & out of cells.

12. Copyright © 2006 Lippincott Williams & Wilkins. The limits of exercise intensity ultimately depend on the rate that cells, extract, conserve, and transfer chemical energy in the food nutrients to the contractile filaments of skeletal muscle Key Point

13. Copyright © 2006 Lippincott Williams & Wilkins. Factors Affecting Bioenergetics Enzymes –Reaction rates: operation rate of enzymes –Enzyme mode of action: how an enzyme reacts with its specific substrate Coenzymes

14. Copyright © 2006 Lippincott Williams & Wilkins. Enzymes Are highly specific protein catalysts Accelerate the forward and reverse reactions Are neither consumed nor changed in the reaction pH and temperature dramatically affect enzyme activity Named for functions they perform “-ase”

15. Copyright © 2006 Lippincott Williams & Wilkins. Enzymes Six major classes of enzymes. 1.Hydrolase: hydrolysis break chemical bonds by insertion of water molecule. 2.Isomerase: convert one isomer to another. 3.Ligase: bond two substrate molecules together 4.Lyase: catalyze the breakage of molecule 5.Transferase: transfer a specific group from one molecule to another. 6.Oxidoreductase: catalyze oxidation – reduction reactions.

16. Copyright © 2006 Lippincott Williams & Wilkins. Reaction Rates The rate of exergonic and endergonic reactions depends on: –Substrate availability –Enzyme availability –Metabolic state of the cell –Cellular conditions (temperature, pH) Energy charge is maintained.

17. Copyright © 2006 Lippincott Williams & Wilkins. Coenzymes Complex nonprotein organic substances facilitate enzyme action by binding the substrate with its specific enzyme Coenzymes are smaller molecules than enzymes Many vitamins serve as coenzymes, e.g. riboflavin ( flavin adenine dinucleotide ) and niacin ( nicotinamide adenine dinucleotide).

18. Copyright © 2006 Lippincott Williams & Wilkins. Phosphate-Bond Energy

19. Copyright © 2006 Lippincott Williams & Wilkins. ATP: The Energy Currency Adenosine triphosphate provides the required energy for all cellular functions Cell’s “energy currency” ATP + H 2 O ↔ ADP + P i + ∆ G (free energy) + heat ATP hydrolysis yields 7.3 kcal of free energy.

20. Copyright © 2006 Lippincott Williams & Wilkins. Structure of Adenosine Triphosphate (ATP)

21. Copyright © 2006 Lippincott Williams & Wilkins. ATP  ADP Cycle is the fundamental mode of energy release in biological systems. Anabolic: use extracted chemical energy from ATP to synthesize new compounds. Catabolic: release energy for biologic work.

22. Copyright © 2006 Lippincott Williams & Wilkins. Catabolism-Anabolism Interactions

23. Copyright © 2006 Lippincott Williams & Wilkins. Synthesized end products Carbohydrates, fats, proteins, and O 2 ADP + Pi ATP Building block precursors H 2 O + CO 2 Anabolism(endergonic) Catabolism (exergonic)

24. Copyright © 2006 Lippincott Williams & Wilkins. How much ATP can the body store? Why do cells store small quantity ?

25. Copyright © 2006 Lippincott Williams & Wilkins. Phosphocreatine Energy rich phosphate compound closely related to ATP. Contains an energy rich phosphoanhydride bond. Insert Figure 3.7

26. Copyright © 2006 Lippincott Williams & Wilkins. Released energy is coupled with energy requirement for re-synthesis of ATP. –For every mole of PCr broken down, 1 mole of ATP synthesized. –The coupled reaction is: Where is PCr stored?

27. Copyright © 2006 Lippincott Williams & Wilkins. Intramuscular High Energy Phosphates 1.How long can high energy phosphates sustain all-out activity? 2.Mobilization of ATP and PCr important in determining anaerobic power.

28. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Human energy dynamics involve transferring energy by chemical bonds. Energy for phosphorylation comes from oxidation of carbohydrate, lipid, and protein macronutrients.

29. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Oxidation reactionOxidation reaction: an element loses electrons (e - ); a compound loses electrons, often accompanied by hydrogen ions (H + ), or it gains oxygen. Reduction reactionReduction reaction: an element gains electrons (e - ); a compound gains electrons, or it loses oxygen.

30. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Oxidation-reduction reactions are coupled. Every oxidation coincides with a reduction. OILRIGOIL RIG: OIL Oxidation Involves Loss RIG Reduction Involves Gain LEOGERLEO the lion says GER: LEO Lose Electrons Oxidation GER Gain Electrons Reduction

31. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Oxidation-reduction reactions are coupled. Every reduction coincides with a oxidation (redox). Cellular oxidation-reduction constitutes mechanism for energy metabolism. Carbohydrate, fat, and protein provide hydrogen atoms for this process.

32. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Hydrogens released from food molecules picked up by coenzyme NAD + & sometimes FAD in cytosol. Substrate oxidizes & loses hydrogens (electrons), NAD + gains a hydrogen & 2 electrons and reduces to NADH, the other H + in fluid FAD also catalyzes dehydro- genations and accepts pairs of electrons.

33. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation NADH and FADH 2 formed in macronutrient breakdown in cytosol carry electrons to cytochromes in mitochondrial membrane. Animation: chemical rxns mitochondrion Cytochromes, a series of iron-protein electron carriers, pass pairs of electrons in bucket brigade fashion on the inner membranes of mitochondrion.

34. Copyright © 2006 Lippincott Williams & Wilkins. Transport of electrons by specific carriers constitutes the respiratory chain or electron transport chain. Cellular Oxidation

35. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation The final electron acceptor (oxidizer) in the respiratory chain is oxygen which forms water. Without oxygen as final oxidizer, respiratory chain cannot proceed and H remain in cellular cytosol. Animation: Electron Transport

36. Copyright © 2006 Lippincott Williams & Wilkins. Oxidative Phosphorylation Oxidative phosphorylation: refers to the phosphorylation of ADP during the electron transport from NADH and FADH 2 to oxygen. Electrochemical energy generated in the ETC is harnessed and transferred to ATP synthase which phosphorylates ADP to ATP.

37. Copyright © 2006 Lippincott Williams & Wilkins. Cellular Oxidation Phosphorylation Phosphorylation: the energy transfer through the phosphate bonds of ATP to other compounds to raise them to a higher activation level Oxidation Oxidation: biologic burning of macronutrients in the body for the energy needed for phosphorylation Occurs on inner lining of mitochondrial membranes Involves transferring electrons from NADH and FADH 2 to molecular oxygen, which release and transfer chemical energy to combine ATP from ADP plus a phosphate ion. During aerobic ATP resynthesis, oxygen combines with hydrogen to form water. More than 90% of ATP synthesis takes place in the respiratory chain by oxidative reactions coupled with phosphorylation.

38. Copyright © 2006 Lippincott Williams & Wilkins. Energy Release from Food

39. Copyright © 2006 Lippincott Williams & Wilkins. Energy Release from Carbohydrate What is the primary function of CHO? The only macronutrient whose potential energy generates ATP anaerobically During light & moderate intensity activity CHO supplies about ????? body’s needs. A continual breakdown of CHO is required so lipid can be used for energy. Carbohydrate

40. Copyright © 2006 Lippincott Williams & Wilkins. Energy Release from Carbohydrate Compare rate of aerobic breakdown of CHO to lipid. Net energy yield per molecule of glucose is ?? moles of ATP. Of 686 kCal from one mole of glucose, only 34% (233 kCals) of the energy is conserved within ATP bonds; the remainder is dissipated as heat Carbohydrate

41. Copyright © 2006 Lippincott Williams & Wilkins. Anaerobic vs Aerobic CHO Anaerobic versus Aerobic CHO Energy Stage 1. Anaerobic Glycolysis (rapid): glucose  2 pyruvate  2 lactate. No oxygen. Stage 2. Aerobic Glycolysis (slow): glucose  2 pyruvate  acetyl CoA  citric acid cycle & electron transport. Oxygen (final electron recipient).

42. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate Glycolysis Glycolysis: a series of 10 enzymatically controlled chemical reactions involving breakdown of glucose to two molecules of pyruvate. Anaerobic Glycolysis: breakdown of glucose to 2 lactates. Glycogenolysis: same reactions but begins with glycogen already within cell. Net energy from glycogen 3 ATP.

43. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate Glycolysis occurs in cell’s cytoplasm. What is energy yield in glycolysis? Energy from glycolysis is useful performing what exercise? How many pairs of hydrogen are released during glycolysis?

44. Copyright © 2006 Lippincott Williams & Wilkins. Anaerobic Glycolysis Carbohydrate Formation of lactic acid occurs when excess H from NADH temporarily combine with pyruvic acid.

45. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate Body disposes of lactic acid in two ways: 1.When sufficient O 2 available within muscles, lactate returns H to pyruvic acid for aerobic metabolism. 2.Cori cycle in liver: gluconeogenesis – make glucose from lactate. Animation: Biochemical Cori Cycle

46. Copyright © 2006 Lippincott Williams & Wilkins. Stage Two of energy release from carbohydrate takes place in the mitochondrion. Two coenzyme A’s pick up the 2 two-carbon acetyl group and transport into mitochondria, releasing carbon dioxide molecules. Coenzyme A then releases the acetyl to begin TCA cycle. Carbohydrate

47. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate

48. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate The citric acid cycle, or tricarboxylic acid cycle, or Kreb’s cycle is a series of 10 enzymatically controlled chemical reactions which begins with oxaloacetate and ends with oxaloacetate. Animation: citric acid cycle What is the most important function of the citric acid cycle? How many ATP are formed directly from substrates?

49. Copyright © 2006 Lippincott Williams & Wilkins. Carbohydrate What is the net energy transfer from the complete catabolism of glucose?

50. Copyright © 2006 Lippincott Williams & Wilkins. Energy Release from Fat Adipocytes –Site of fat storage and mobilization –95% of an adipocyte’s volume is occupied by triacylglycerol (TG) fat droplets –Lipolysis splits TG molecules into glycerol and three water-soluble free fatty acids (FFA) –Catalyzed by hormone-sensitive lipase Fat

51. Copyright © 2006 Lippincott Williams & Wilkins. Transport and Uptake of Free Fatty Acids After diffusing into the circulation, FFA are transported within the circulation bound to albumin FFA are then taken up by active skeletal muscle in proportion to their flow and concentration Fat

52. Copyright © 2006 Lippincott Williams & Wilkins. Breakdown of Glycerol and Fatty Acids Glycerol –Is converted to 3-phosphoglyceraldehyde, an intermediate glycolytic metabolite FFA –Are transformed into acetyl–CoA in the mitochondria during  -oxidation –A process that successively releases 2- carbon acetyl fragments split from long fatty acid chains Fat

53. Copyright © 2006 Lippincott Williams & Wilkins. Fat Fuel reserves from fat represents about 60,000 to 100,000 kcals in fat cells and 30,000 in intramuscular triglycerides. Carbohydrate reserves is <2,000 kcal. Before energy release from fat: lypolysis. FA diffuse from adipocyte into blood, bind to albumin & delivered to tissues.

54. Copyright © 2006 Lippincott Williams & Wilkins. Beta Oxidation Fat

55. Copyright © 2006 Lippincott Williams & Wilkins. Did You Know? As carbohydrate levels decrease, the availability of oxaloacetate may become inadequate, which impairs fat catabolism. Fats burn in a carbohydrate flame. Fat

56. Copyright © 2006 Lippincott Williams & Wilkins. Excess macronutrients convert to fat. Any excess carbohydrate, lipid, or protein readily converted to fatty acid.

57. Copyright © 2006 Lippincott Williams & Wilkins. Energy Release from Protein Protein can be used as energy substrate during endurance-type exercise. To provide energy a.a. must be converted to usable form.

58. Copyright © 2006 Lippincott Williams & Wilkins. Metabolic Mill Molecules degraded to few simple units, mostly acetyl CoA. Notice reversibility except pyruvic acid to acetyl CoA. Each pathway has rate- limiting enzyme. Cellular [ADP] is most important factor that affects enzymes controlling energy metabolism.

59. Copyright © 2006 Lippincott Williams & Wilkins. References Axen & Axen. 2001. Illustrated Principles of Exercise Physiology. Prentice Hall. Katch, McArdle, Katch. 2011. Essentials of Exercise Physiology, 4 th ed. Image Bank. Lippincott Williams & Wilkens.