Bioenergetics and Thermodynamics: Energy Transformations in Living Organisms

1. CHAPTER 3 Bioenergetics, Enzymes, and Metabolism

2. 3.1 Bioenergetics • The study of the various types of energy transformations that occur in living organisms.

3. The Laws of Thermodynamics and the Concept of Entropy • Energy – capacity to do work, or the capacity to change or move something. • Thermodynamics – the study of the changes in energy that accompany events in the universe.

4. The First Law of Thermodynamics (1) • The first law of thermodynamics – the law of conservation of energy. • Energy can neither be created nor destroyed. • Transduction – conversion of energy from one form to another. • Electric energy can be transduced to mechanical energy when we plug in a clock.

5. The First Law of Thermodynamics (2) • Cells are capable of energy transduction. • Chemical energy is stored in certain biological molecules, such as ATP. • Chemical energy is converted to mechanical energy when heat is released during muscle contraction.

6. The First Law of Thermodynamics (3) • Energy transduction in the biological world: conversion is the conversion of sunlight into chemical energy – photosynthesis. • Animals, such as fireflies and luminous fish, are able to convert chemical energy back to light.

7. The First Law of Thermodynamics (4) • The universe can be divided into system and surroundings. • The system is a subset of the universe under study. • The surroundings are everything that is not part of the system. • The energy of the system is called the internal energy (E), and its change during a transformation is called ΔE.

8. The First Law of Thermodynamics (5) • The first law of thermodynamics: ΔE = Q – W, where Q is the heat energy and W is the work energy. • When there is energy transduction (ΔE) in a system, heat content may increase or decrease. • Reactions that lose heat are exothermic. • Reactions that gain heat are endothermic. • The first law does not predict whether an energy change will be positive or negative.

9. The First Law of Thermodynamics (6)

10. The Second Law of Thermodynamics (1) • The second law of thermodynamics: events in the universe tend to proceed from a state of higher energy to a state of lower energy. • Such events are called spontaneous, they can occur without the input of external energy. • Loss of available energy during a process is the result of a tendency for randomness to increase whenever there is a transfer of energy.

11. The Second Law of Thermodynamics (2) • Entropy is a measure of randomness or disorder. • It is energy not available to do additional work. • Loss of available energy equal TΔS, where ΔS is the change in entropy.

12. The Second Law of Thermodynamics (3) • Every event is accompanied by an increase in the entropy of the universe. • Entropy associated with random movements of particles or matter. • Living systems maintain a state of order, or low entropy

13. Free Energy (1) • The first and second laws of thermodynamics can be combined and expressed mathematically. • Equation: ΔH = ΔG + TΔS • Free energy, ΔG, is the energy available to do work. • Spontaneity of the reaction is ΔG, if <0 the reaction is exergonic, if >0 it is endergonic. • Spontaneity depends on both enthalpy and entropy.

14. Free Energy (2)

15. Free-Energy Changes in Chemical Reactions (1) • All chemical reactions are theoretically reversible. • All chemical reactions spontaneously proceed toward equilibrium (Keq = [C][D]/[A][B]). • The rates of chemical reactions are proportional to the concentration of reactants. • At equilibrium, the free energies of the products and reactants are equal (ΔG = 0).

16. Free-Energy Changes in Chemical Reactions (2) • Free energy changes of reactions are compared under standard conditions. • The standard free energy changes, ΔG°’, are described for each reaction under specific conditions. • Standard conditions are not representative of cellular conditions, but are useful to make comparisons. • Standard free energy changes are related to equilibrium: ΔG°’ = -RT ln K’eq

17. Calculation of free energy changes (1) • Non-standard conditions are corrected for prevailing conditions. • Equation: ΔG = ΔG°’ + RT ln Keq. • Prevailing conditions may cause ΔG to be negative, even when G°’ is positive. • Making ΔG negative may involve coupling endergonic and exergonic reactions in a sequence. • Simultaneously coupled reactions have a common intermediate. • ATP hydrolysis is often coupled to endergonic reactions in cells.

18. Calculation of free energy changes (1)

19. Coupling Endergonic and Exergonic Reactions

20. Coupling Endergonic and Exergonic Reactions

21. Equilibrium versus Steady-State Metabolism • Cellular metabolism is nonequilibrium metabolism. • Cells are open thermodynamic systems. • Cellular metabolism exists in a steady state. • Concentrations of reactants and products remain constant, but not at equilibrium. • New substrates enter and products are removed. • Maintaining a steady state requires a constant input of energy, whereas maintaining equilibrium does not.

22. Steady State versus Equilibrium

23. 3.2 Enzymes as Biological Catalysts • Enzymes are catalysts that speed up chemical reactions. • Enzymes are almost always proteins. • Enzymes may be conjugated with nonprotein components. • Cofactors are inorganic enzyme conjugates. • Coenzymes are organic enzyme conjugates.

24. Properties of Enzymes (1) • Are present in cells in small amounts. • Are not permanently altered during the course of a reaction. • Cannot affect the thermodynamics of reactions, only the rates. • Are highly specific for their particular reactants called substrates. • Produce only appropriate metabolic products. • Can be regulated to meet the needs of a cell.

25. Properties of Enzymes (2)

26. Overcoming the Activation Energy Barrier • A small energy input, the activation energy (EA) is required for any chemical transformation. • The EA barrier slows the progress of thermodynamically unstable reactants. • Reactant molecules that reach the peak of the EA barrier are in the transition state.

27. Enzymes lower the activation energy • Without an enzyme, only a few substrate molecules reach the transition state. • With a catalyst, a large proportion of substrate molecules can reach the transition state.

28. The Active Site • An enzyme interacts with its substrate to form an enzyme-substrate (ES) complex. • The substrate binds to a portion of the enzyme called the active site. • The active site and the substrate have complementary shapes that allow substrate specificity.

29. The Active Site

30. Mechanisms of Enzyme Catalysis (1) • Substrate orientation means enzymes hold substrates in the optimal position of the reaction.

31. Mechanisms of Enzyme Catalysis (2) • Changes in the reactivity of the substrate temporarily stabilize the transition state. • Acidic or basic R groups on the enzyme may change the charge of the substrate. • Charged R groups may attract the substrate. • Cofactors of the enzyme increase the reactivity of the substrate by removing or donating electrons.

32. Mechanisms of Enzyme Catalysis (3) • Inducing strain in the substrate. • Shifts in the conformation after binding cause an induced fit between enzyme and the substrate. • Covalent bonds of the substrate are strained.

33. Mechanisms of Enzyme Catalysis (4) • Conformational changes and catalytic intermediates. • Various changes in atomic and electronic structure occur in both the enzyme and substrate during a reaction. • Using time-resolved crystallography, researchers have determined the three-dimensional structure of an enzyme at successive stages during a reaction

34. Mechanisms of Enzyme Catalysis (4) • Conformational changes and catalytic intermediates. • Various changes in atomic and electronic structure occur in both the enzyme and substrate during a reaction. • Using time-resolved crystallography, researchers have determined the three-dimensional structure of an enzyme at successive stages during a reaction

35. Enzyme Kinetics (1) • Kinetics is the study of rates of enzymatic reactions under various experimental conditions. • Rates of enzymatic reactions increase with increasing substrate concentrations until the enzyme is saturated. • At saturation every enzyme s working at maximum capacity. • The velocity at saturation is called maximal velocity, Vmax. • The turnover number is the number of substrate molecules converted to product per minute per enzyme molecule at Vmax.

36. Enzyme Kinetics (2) • The Michaelis constant (KM) is the substrate concentration at one-half of Vmax. • Units of KM are concentration units. • The KM may reflect the affinity of the enzyme for the substrate.

37. Enzyme Kinetics (3) • Plots of the inverses of velocity versus substrate concentrations, such as the Lineweaver-Burk plot, facilitate estimating Vmax and KM. • Temperature and pH can affect enzymatic reaction rates.

38. Enzyme Kinetics (4)

39. Enzyme Kinetics (4)

40. Enzyme Inhibitors (1) • Enzyme inhibitors slow the rates for enzymatic reactions. • Irreversible inhibitors bind tightly to the enzyme. • Reversible inhibitors bind loosely to the enzyme. • Competitive inhibitors compete with the enzyme for active sites • Usually resemble the substrate in structure. • Can be overcome with high substrate/inhibitor ratios.

41. Enzyme Inhibitors (2)

42. Enzyme Inhibitors (3) • Noncompetitive inhibitors • Bind to sites other than active sites and inactivate the enzyme. • The maximum velocity of enzyme molecules cannot be reached. • Cannot be overcome with high substrate/inhibitor ratios.

43. The Human Perspective: The Growing Problem of Antibiotic Resistance (1) • Antibiotics target human metabolism without harming the human host. • Enzymes involved in the synthesis of the bacterial cell wall. • Components of the system by which bacteria duplicate, transcribe, and translate their genetic information. • Enzymes that catalyze metabolic reactions specific to bacteria.

44. The Human Perspective: The Growing Problem of Antibiotic Resistance (2) • Antibiotics have been misused with dire consequences. • Susceptible cells are destroyed, leaving rare and resistant cells to survive and replicate. • Bacteria become resistant to antibiotics by acquiring genes from other bacteria by various mechanisms.

45. 3.3 Metabolism • Metabolism is the collection of bio-chemical reactions that occur within a cell. • Metabolic pathways are sequences of chemical reactions. • Each reaction in the sequence is catalyzed by a specific enzyme. • Pathways are usually confined to specific locations. • Pathways convert substrates into end products via a series of metabolic intermediates.

46. Catabolicpathways break down complex substrates into simple end products. Provide raw materials for the cell. Provide chemical energy for the cell. Anabolic pathways synthesize complex end products from simple substrates. Require energy. Use ATP and NADPH from catabolic pathways. An Overview of Metabolism (1)

47. An Overview of Metabolism (2) • Anabolic and catabolic pathways are interconnected. • In stage I, macromolecules are hydrolyzed into their building blocks. • In stage II, building blocks are further degraded into a few common metabolites. • In stage III, small molecular weight metabolites like acetyl-CoA are degraded yielding ATP.

48. Oxidation and Reduction: A Matter of Electrons (1) • Oxidation-reduction (redox) reactions involve a change in the electronic state of reactants. • When a substrate gains electrons, it is reduced. • When a substrate loses electrons, it is oxidized. • When one substrate gains or loses electrons, another substance must donate or accept those electrons. • In a redox pair, the substrate that donates electrons is a reducing agent. • The substrate that gains electrons is an oxidizing agent.

49. Oxidation and Reduction: A Matter of Electrons (1)

50. The Capture and Utilization of Energy • Reduced atoms can be oxidized, releasing energy to do work. • The more a substance is reduced, the more energy that can be released. • Glycolysis is the first stage in the catabolism of glucose, and occurs in the soluble portion of the cytoplasm. • The tricarboxylic (TCA) cycle is the second stage and it occurs in the mitochondria of eukaryotic cells.