1. Figure 8-01

2. This new material we begin today will be on exam #2 Material for exam #1 (March 4) will include these textbook chapters: Chapter 3-water Chapter 4-Carbon and the Molecular Diversity of Life (especially functional groups) Chapter 6-Cell Structure and Function Chapter 7-Cell Membranes

3. An Introduction to Metabolism I. Metabolism, Energy and Life The chemistry of life is organized into metabolic pathways Organisms transform energy The energy transformations of life are subject to two laws of thermodynamics Organisms live at the expense of free energy ATP powers cellular work by coupling exergonic to endergonic reactions II. Enzymes Enzymes speed up metabolic reactions by lowering energy barriers Enzymes are substrate-specific The active site is an enzyme’s catalytic center III. The Control of Metabolism Metabolic control often demands allosteric regulation The location of enzymes within a cell helps to order metabolism

4. Cell Energetics Energy definition-capacity to do work. In terms of cell, what are some types of work that have to be done to stay alive?

5. Figure 6.2x1 Kinetic and potential energy: dam

6. Important forms of kinetic and potential energy for living organisms Kinetic-sunlight; heat Potential-chemical bond energy (glucose, ATP, etc.)

7. Cell Energetics are Governed by the Laws of Thermodynamics First Law of Thermodynamics (law of Conservation of Energy) Energy cannot be created or destroyed but it can be changed in form. Energy transformation is permissible (life depends on this happening)- sunlight  chemical

8. LE 8-2 On the platform, the diver has more potential energy. Diving converts potential energy to kinetic energy. Climbing up converts kinetic energy of muscle movement to potential energy. In the water, the diver has less potential energy.

9. Second Law of Thermodynamics All matter tends to spontaneously move to the greatest possible state of stability (bonding) All matter tends to spontaneously move from areas of higher concentration to lower concentration (diffusion) All matter tends to spontaneously move from states of higher free energy (less stable, more concentrated) to states of lower free energy (more stable, less concentrated)

10. Entropy-Another way to look at the 2 nd law of Thermodynamics We’ve defined the 2nd law previously in terms of stability and free energy. Another way is to understand the 2 nd Law is to use the concept of entropy. Entropy is the measure of the disorganization of a system All systems spontaneously assume the state of greatest entropy.

11. Cells, entropy, and the 2 nd Law of Thermodynamics Cells are very organized (low entropy) How can a cell exist in the face of the 2nd Law (maintain organization)? Expend energy. It’s work to stay alive! The key is that the cell decreases its entropy at the expense of increasing the entropy of its surroundings. Cells take ordered (high energy molecules from the environment and return unordered waste products). The cell is an open system (can exchange energy with its environment). Can a closed system maintain a state of low entropy?

12. LE 8-3 Chemical energy Heat CO 2 First law of thermodynamicsSecond law of thermodynamics H2OH2O

13. What does the 2nd Law of Thermodynamics say about Life?

14. Life is improbable. Life cannot violate the principle that entropy increases. Living things live at the expense of their environment (living things are able to maintain a state of decreased entropy because the entropy of the entire universe (system + surroundings) is increasing Life can only exist if energy is constantly being expended.

15. What form of energy does the cell use to maintain its organization? ATP ATP cycle

16. LE 8-8 Phosphate groups Ribose Adenine

17. LE 8-9 Adenosine triphosphate (ATP) Energy PP P PP P i Adenosine diphosphate (ADP) Inorganic phosphate H2OH2O + +

18. ATP hydrolysis “releases” energy so that cellular work can be done bond breaking versus bond formation

19. Why does ATP hydrolysis “release” energy?

20. ATP and cellular work How does ATP hydrolysis power cellular work? Phosphorylation and dephosphorylation of proteins

21. LE 8-11 NH 2 Glu P i P i P i P i NH 3 P P P ATP ADP Motor protein Mechanical work: ATP phosphorylates motor proteins Protein moved Membrane protein Solute Transport work: ATP phosphorylates transport proteins Solute transported Chemical work: ATP phosphorylates key reactants Reactants: Glutamic acid and ammonia Product (glutamine) made + + +

22. How is ATP produced? Cellular respiration (cash versus check analogy) Difference in autotrophs and heterotrophs

23. LE 8-UN141 Enzyme 1 AB Reaction 1 Enzyme 2 C Reaction 2 Enzyme 3 D Reaction 3 Product Starting molecule

24. Metabolism and Spontaneous reactions Previously stated that catabolic reactions were spontaneous and anabolic were not spontaneous.

25. Metabolism Cell respiration is one example of a metabolic pathway. The chemistry of life is organized into metabolic pathways (complex and regulated by enzymes). (street analogy). 2 types of metabolic pathways a. catabolic-degradative, energy releasing (downhill), oxidative, spontaneous b. anabolic-synthetic, energy requiring (up hill), reduction, not spontaneous

26. Figure 6.1 The complexity of metabolism

27. Spontaneous reactions What are they? They happen on their own without an input of energy They are a result of the 2 nd law of Thermodynamics

28. LE 8-5 Gravitational motionDiffusionChemical reaction

29. What determines spontaneity of a chemical reaction? A +B  C+D (substrate  products) Spontaneous-decrease in free energy (downhill), not spontaneous-increase free energy (uphill) What is free energy? Energy available to do work. G=H-TS Maximum amount of free energy that can be harvested from a reaction is the free energy change of the reaction (  G).  G=  H-T  S  G-energy available to do work (keep cells alive)  H-total energy  S-energy unavailable to do work

30. How is  G determined for a reaction? FE of products –FE of reactants. a. If  G is negative (the free energy of the reactants is > fe of products), the reaction is spontaneous (downhill). b. If  G is positive (the fe of the reactants is < fe of products), the reaction is not spontaneous (uphill). c. If  G is 0-no free energy difference. The reaction is at equilibrium. No work can be done from that reaction.

31. Figure 6.5 The relationship of free energy to stability, work capacity, and spontaneous change

32. LE 8-6a Reactants Energy Products Progress of the reaction Amount of energy released (  G < 0) Free energy Exergonic reaction: energy released

33. LE 8-6b Reactants Energy Products Progress of the reaction Amount of energy required (  G > 0) Free energy Endergonic reaction: energy required

34. Exergonic and Endergonic reactions Reactions can also be classified based on free energy changes. Endergonic and exergonic reactions.

35. Differences in Exergonic and Endergonic Reactions

36. Metabolic reactions and equilibrium What would be the problem for a cell if its metabolic reactions (especially catabolic ones) were allowed to reach equilibrium? Cellular metabolism is normally not allowed to reach equilibrium. Metabolism generally involves multi-step pathways where the product of one reaction becomes the substrate of the next reaction. This strategy only works because cells are open systems

37. LE 8-7a  G = 0 A closed hydroelectric system  G < 0

38. LE 8-7b An open hydroelectric system  G < 0

39. LE 8-7c A multistep open hydroelectric system  G < 0

40. Relationship between catabolic and anabolic reactions Coupling endergonic and exergonic reactions example.

41. LE 8-12 P i ADP Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy- yielding processes) ATP +

42. LE 8-10 Endergonic reaction:  G is positive, reaction is not spontaneous Exergonic reaction:  G is negative, reaction is spontaneous  G = +3.4 kcal/mol  G = –7.3 kcal/mol  G = –3.9 kcal/mol NH 2 NH 3 Glu Glutamic acid Coupled reactions: Overall  G is negative; together, reactions are spontaneous AmmoniaGlutamine ATP H2OH2O ADP P i + + +

43. LE 8-13 Sucrose C 12 H 22 O 11 Glucose C 6 H 12 O 6 Fructose C 6 H 12 O 6

44. Enzymes Characteristics

45. LE 8-17 Enzyme-substrate complex Substrates Enzyme Products Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Active site (and R groups of its amino acids) can lower E A and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction. Substrates are converted into products. Products are released. Active site is available for two new substrate molecules.

46. LE 8-16 Substrate Active site Enzyme Enzyme-substrate complex

47. Catalysis Properties of a catalyst How do enzymes increase the rate of a chemical reaction Why don’t enzymes alter the  of a reaction?

48. LE 8-14 Transition state CD A B EAEA Products CD A B  G < O Progress of the reaction Reactants C D A B Free energy

49. LE 8-15 Course of reaction without enzyme E A without enzyme  G is unaffected by enzyme Progress of the reaction Free energy E A with enzyme is lower Course of reaction with enzyme Reactants Products

50. Factors influencing enzyme activity

51. Temperature pH

52. LE 8-18a Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant bacteria Temperature (°C) Optimal temperature for two enzymes 0 20 40 60 80100 Rate of reaction

53. LE 8-18b Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) pH Optimal pH for two enzymes 0 Rate of reaction 1 23 45 67 8 910

54. Factors influencing enzyme activity Inhibitors: A. nonreversible B. Reversible 1.Competitive inhibition 2.Noncompetitive inhibition

55. LE 8-19a Substrate Active site Enzyme Normal binding A substrate can bind normally to the active site of an enzyme.

56. LE 8-19b Competitive inhibitor Competitive inhibition A competitive inhibitor mimics the substrate, competing for the active site.

57. LE 8-19c Noncompetitive inhibitor Noncompetitive inhibition A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions.

58. A practical application of noncompetitive inhibition Feedback Inhibition Purpose of feedback inhibition

59. LE 8-UN159 O M L N S R Q P – – –

60. LE 8-21 Active site available Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Enzyme 2 Intermediate A Isoleucine used up by cell Feedback inhibition Active site of enzyme 1 can’t bind theonine pathway off Isoleucine binds to allosteric site Enzyme 3 Intermediate B Enzyme 4 Intermediate C Enzyme 5 Intermediate D End product (isoleucine)