1. CHAPTER 8 AN INTRODUCTION TO METABOLISM

2. Learning objectives  Understand why energy is necessary for sustaining life.  Understand how organisms transform matter and energy in accordance with the laws of thermodynamics.  Recognize that energy conversions are dependent on metabolic pathways.  Understand the role of enzyme inhibition in metabolic pathways and predict the effects of enzyme deficiency due to genetic disease.  Apply knowledge of converging metabolic pathways and enzyme inhibition to understand the treatment options for a metabolic disease.

3. The totality of an organism’s chemical reactions is called 1. 1.Metabolism 2. 2.Catabolism 3. 3.Anabolism 4. 4.Recreation 5. 5.Perspiration

4. Living Organisms and Order a)The laws of thermodynamics do not apply to living organisms. b)Living organisms create order by using energy from the sun. c)Living organisms create order locally, but the energy transformations generate waste heat that increases the entropy of the universe. How do living organisms create macromolecules, organelles, cells, tissues, and complex higher-order structures?

5. 1.Catabolic pathways  breaking down complex molecules into simpler compounds with a release of energy (downhill reactions)  degradative pathways that provide energy and raw materials for cell  EX: cellular respiration -- glucose is converted into carbon dioxide, water and energy Two types of metabolic pathways:

6. 2. Anabolic pathways  Building complex molecules from simpler ones with the input of energy  Uphill reactions because they consume energy  Biosynthetic pathways = total of all reactions involved in synthesis of macromolecules (proteins, lipids, etc.)

7. Energy, the capacity to cause change, released by catabolic pathways is used to drive anabolic pathways 1. 1.True 2. 2.False

8.  Kinetic energy = energy of motion, energy in process of doing work  Potential energy = energy that matter possesses because of its location or structure  Stored energy (EX: water behind a dam)  Chemical bond energy = form of potential energy stored in bonds that hold atoms together in molecules (due to arrangement of atoms) Forms of energy

9.  Thermodynamics = study of energy transformations in a collection of matter  System = collection of matter under study  Surroundings =everything outside the system  Two types of systems: 1.Isolated system = collection of matter under study that is isolated from its surroundings 2.Open system = one in which energy can be transferred between system and surroundings Energy transformations of life are subject to two laws of thermodynamics

10. Energy can neither be created nor can it be destroyed, but it can be transferred from one form to another 1. 1.True 2. 2.False

11. First law of thermodynamics  States:  Energy can be transferred and transformed  Energy cannot be created or destroyed  EX: Plants transform light to chemical energy; they do not create energy  Total amount of energy in the universe is constant…if something gains energy, something else must lose it

12. Every energy transfer or transformation increases the entropy of the universe. 1. 1.True 2. 2.False

13.  States that whenever energy is converted from one form to another, some energy is lost, usually as heat  Which means that the amount of disorder (randomness) in universe is always increasing…all systems tend toward maximum randomness Second law of thermodynamics

14. Free Energy, Enthalpy, and Entropy a)the change in enthalpy (  H) is negative. b)the change in enthalpy (  H) is positive, but the change in entropy is greater. c)the reaction is endergonic, because it absorbs heat. d)the reaction must be coupled to an exergonic reaction. e)the reaction cannot occur spontaneously. When sodium chloride (table salt) crystals dissolve in water, the temperature of the solution decreases. This means that, for dissociation of Na + and Cl – ions,

15.  A system at equilibrium is at maximum stability  Chemical equilibrium  rate of forward and backward reactions are equal and there is no change in the concentration of products or reactants  What is free energy at equilibrium?   G = 0 and system can do no work Figure 8.7 A A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium. ∆G < 0 ∆G = 0

16.  Cells maintain disequilibrium because they are open systems with a constant flow of material in and out of the cell Fig. 8.7b (b) An open hydroelectric system ∆G < 0

17.  Cells have mechanisms to ensure that equilibrium is never reached  product of one reaction becomes reactant in the next step of metabolic pathway  Cell respiration pathways release free energy in a series of reactions, not in a single step. A cell continues to do work throughout its life Fig. 8.7c (c) A multistep open hydroelectric system ∆G < 0

18. C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O  G = -636 kcal/mol, so this is an example of In this reaction, C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O  G = -636 kcal/mol, so this is an example of 1. 1.Photosynthesis 2. 2.Exergonic reaction 3. 3.Endergonic reaction

19. Rate of a Chemical Reaction a)The glucose molecules lack the activation energy at room temperature. b)There is too much CO 2 in the air. c)CO 2 has higher energy than glucose. d)The formation of six CO 2 molecules from one glucose molecule decreases entropy. e)The water molecules quench the reaction. The oxidation of glucose to CO 2 and H 2 O is highly exergonic:  G = –636 kcal/mole. Why doesn’t glucose spontaneously combust?

20. Metabolism: Exergonic and Endergonic Reactions

21. Free Energy a)The reaction could be coupled to power an endergonic reaction with a  G of  8.8 kcal/mol. b)The reaction would result in a decrease in entropy (S) and an increase in the energy content (H) of the system. c)The reaction would result in an increase in entropy (S) and a decrease in the energy content (H) of the system. d)The reaction would result in products with a greater free- energy content than in the initial reactants. A reaction has a ∆G of  5.6 kcal/mol. Which of the following would most likely be true?

22. Chemical Reactions: Activation Energy (EA)   Every chemical reaction involves bond breaking and bond forming   A chemical reaction generally involves the transformation of a molecule (reactant) into another (product) after the transition state has been overcome   Activation energy is the energy required for such transformation

23. Chemical Reactions: Enzymes Lower the Activation Energy Barrier

24. Enzyme-Catalyzed Reactions a)a b)b c)c d)d e)e In the energy diagram below, which of the lettered energy changes would be the same in both the enzyme-catalyzed and uncatalyzed reactions?

25. Enzymes: What Are They?   Enzymes are catalysts, molecules that lower the activation energy barrier required for a reaction to occur. Thus, catalysts speed up chemical reactions   Enzymes are proteins or nucleic acids (RNA). Enzymes made of RNA are called ribozymes   Enzymes carry the suffix ase   Enzymes are substrate specific Bacillus licheniformis a-amylase (1BLI)

26. Enzymes: Specificity of Substrate   The reactant an enzyme acts on is referred to as the enzyme’s substrate   The enzyme binds to the substrate, thus forming the enzyme-substrate complex   The reaction catalyzed by the enzyme produces end products Substrate + Enzyme → End Product(s) MovieMovie on how enzymes work - http://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2/animation__ho w_enzymes_work.html

27. In the following diagram, there are ___ enzymes 1. 1.0 2. 2.5 3. 3.7 4. 4.11 5. 5.Cannot be estimated

28. Specificity of substrate Sucrase catalyzes the hydrolysis of sucrose into glucose and fructose

29. Factors Influencing Enzyme Activity   Concentration: In general, the more concentration of substrate, the more frequently the enzyme’s active site interact. However, high concentrations of substrate can saturate the enzyme   Temperature and pH: Enzymes are very sensitive to slight changes of pH and temperature. Each enzyme has an optimal value of pH and temperature to which is most active   Enzyme regulation

30. (a) Normal binding(b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Enzyme Competitive inhibitor Noncompetitive inhibitor

31. Regulation of enzyme activity helps control metabolism  Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated  A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes

32. Allosteric Regulation of Enzymes  Allosteric regulation may either inhibit or stimulate an enzyme’s activity  Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site

33. Regulatory site (one of four) (a) Allosteric activators and inhibitors Allosteric enzyme with four subunits Active site (one of four) Active form Activator Stabilized active form Oscillation Nonfunctional active site Inactive form Inhibitor Stabilized inactive form

34. Inactive form Substrate Stabilized active form (b) Cooperativity: another type of allosteric activation

35.  Cooperativity is a form of allosteric regulation that can amplify enzyme activity  One substrate molecule primes an enzyme to act on additional substrate molecules more readily  Cooperativity is allosteric because binding by a substrate to one active site affects catalysis in a different active site

36. Enzyme Inhibitors a)competitive inhibitors. b)noncompetitive inhibitors. c)allosteric regulators. d)prosthetic groups. e)feedback inhibitors. Vioxx and other prescription nonsteroidal anti- inflammatory drugs (NSAIDs) are potent inhibitors of the cycloxygenase-2 (COX-2) enzyme. High substrate concentrations reduce the efficacy of inhibition by these drugs. These drugs are

37. Feedback Inhibition  In feedback inhibition, the end product of a metabolic pathway shuts down the pathway  Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed

38. Active site available Isoleucine used up by cell Feedback inhibition Active site of enzyme 1 is no longer able to catalyze the conversion of threonine to intermediate A; pathway is switched off. Isoleucine binds to allosteric site. Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Intermediate B Intermediate C Intermediate D Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 End product (isoleucine)

39. Competitive regulation involves 1. 1.Influence of a compound that binds to the active site of the enzyme. 2. 2.Influence of a compound that binds to a site different from the active site 3. 3.Such a term is not associated with enzyme regulation

40. Which of these is an incorrect connection? 1. 1.Competitive 2. 2.Non-competitive 3. 3.Substrate-Enzyme 4. 4.None of them 5. 5.All of them123

41. Allosteric inhibition is when the inhibitor binds to a site other than the active site on the enzyme 1. 1.True 2. 2.False

42. Feedback inhibition is not one of the following: 1. 1.A metabolic pathway is switched off by molecules that regulate the activity of the enzyme 2. 2.The regulatory molecules are the end product(s) 3. 3.End product(s) can perform competitive inhibition 4. 4.End product(s) can perform allosteric inhibition 5. 5.All the above statements are correct 6. 6.None of the above statements are correct

43. ATP powers cellular work by coupling exergonic reactions to endergonic reactions  A cell does three main kinds of work  Chemical  Transport  Mechanical  To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one  Most energy coupling in cells is mediated by ATP

44. The Structure and Hydrolysis of ATP  ATP (adenosine triphosphate) is the cell’s energy shuttle  ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups

45. (a) The structure of ATP Phosphate groups Adenine Ribose

46. Adenosine triphosphate (ATP) Energy Inorganic phosphate Adenosine diphosphate (ADP) (b) The hydrolysis of ATP

47.  The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis  Energy is released from ATP when the terminal phosphate bond is broken  This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves  Movie summarizing the energy transfer and ATP’s role - http://wps.prenhall.com/wps/media/objects/ 2688/2752944/Web_Tutorials/06_A01.swf Movie

48. The hydrolysis of ATP: ATP  H 2 O → ADP  Pi is exergonic, with a  G of  7.3 kcal/mol under standard conditions. What is the source of the 7.3 kcal/mol released in this reaction? a)breaking the terminal phosphate bond in ATP b)the increase in entropy from breaking apart ATP c)both the energy released from breaking the terminal phosphate bond and the increase in entropy d)the difference between the potential energy in the bonds of ATP and the water molecule, minus the potential energy in the bonds of ADP and Pi

49. How the Hydrolysis of ATP Performs Work  The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP  In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction  Overall, the coupled reactions are exergonic

50. Glutamic acid Ammonia Glutamine (b) Conversion reaction coupled with ATP hydrolysis Glutamic acid conversion to glutamine (a) (c) Free-energy change for coupled reaction Glutamic acid Glutamine Phosphorylated intermediate Glu NH 3 NH 2 Glu  G Glu = +3.4 kcal/mol ATP ADP NH 3 Glu P P i ADP Glu NH 2  G Glu = +3.4 kcal/mol Glu NH 3 NH 2 ATP  G ATP =  7.3 kcal/mol  G Glu = +3.4 kcal/mol +  G ATP =  7.3 kcal/mol Net  G =  3.9 kcal/mol 1 2

51.  ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant  The recipient molecule is now called a phosphorylated intermediate

52. Transport protein Solute ATP P P i ADP P i ADP ATP Solute transported Vesicle Cytoskeletal track Motor proteinProtein and vesicle moved (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed. (a) Transport work: ATP phosphorylates transport proteins.

53. Energy from catabolism (exergonic, energy-releasing processes) Energy for cellular work (endergonic, energy-consuming processes) ATP ADPP i H2OH2O

54. The Regeneration of ATP  ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)  The energy to phosphorylate ADP comes from catabolic reactions in the cell  The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways