1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 8 An Introduction to Metabolism

2. Overview: The Energy of Life Living cells use thousands of chemical reactions Cells extract energy & apply it to perform work Some organisms even convert energy to light, as in bioluminescence Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Figure 8.1 What causes the bioluminescence in these fungi?

3. Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics Metabolism- all of an organism’s chemical reactions Metabolism is an emergent property of life due to interactions between molecules within the cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. Organization of the Chemistry of Life into Metabolic Pathways Metabolic pathways begin with a specific molecule and end with a product Each step is catalyzed by a specific enzyme Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-UN1 Enzyme 1Enzyme 2Enzyme 3 D CB A Reaction 1Reaction 3Reaction 2 Starting molecule Product

5. Catabolic pathways break down complex molecules & release energy Cellular respiration, the breakdown of glucose in the presence of oxygen, catabolic a pathway Anabolic pathways use energy to build complex molecules from simple ones The synthesis of protein is a form of anabolism Bioenergetics is the study of how organisms manage their energy resources Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

6. Forms of Energy Energy- the capacity to cause change – It exists in various forms, some of which can perform work Kinetic energy-energy associated with motion Heat (thermal energy)- kinetic energy from the movement of atoms or molecules Potential energy-energy due to the location or structure of matter Chemical energy- potential energy waiting to be released in a reaction Energy can be converted from one form to another Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Animation: Energy Concepts Animation: Energy Concepts

7. Fig. 8-2 Climbing up converts the kinetic energy of muscle movement to potential energy. A diver has less potential energy in the water than on the platform. Diving converts potential energy to kinetic energy. A diver has more potential energy on the platform than in the water. Figure 8.2 Transformations between potential and kinetic energy

8. The Laws of Energy Transformation Thermodynamics- study of energy transformations A closed system, such as liquid in a thermos, is isolated from its surroundings An open system transfers energy and matter between the system and its surroundings Organisms are open systems Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9. The First Law of Thermodynamics First Law of Thermodynamics- the energy of the universe is constant: – Energy can be transferred and transformed, but not created or destroyed The 1 st law is also called the Principle of Conservation of Energy Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

10. The Second Law of Thermodynamics The second law of thermodynamics states: – Every energy transfer or transformation increases entropy (disorder) in the universe During every energy transfer or transformation, some energy is unusable, and is lost as heat H2OH2O Fig. 8-3 (a) First law of thermodynamics (b) Second law of thermodynamics Chemical energy Heat + H2OH2O CO 2

11. Living cells convert organized forms of energy to heat Spontaneous processes don’t need energy but can happen quickly or slowly If a process occurs without energy, it must increase the entropy of the universe Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

12. Biological Order and Disorder Organisms replace ordered forms of matter and energy with less ordered forms (breaking down food to molecules, atoms, & energy) Cells make ordered structures from less ordered materials (using the atoms, molecules & energy extracted from the food) Energy flows into an ecosystem as light and exits as heat Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

13. Concept 8.2: The free-energy change of a reaction tells us if the reaction occurs spontaneously Biologists want to know which reactions are spontaneous and which need energy They must determine energy changes that occur in chemical reactions Free-Energy Change,  G The free energy in a living system can do work if the temperature & pressure are uniform, – ex. cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

14. The change in free energy (∆G) during a process relates to the change in enthalpy, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T): ∆G = ∆H – T∆S Only processes with a negative ∆G are spontaneous and can be harnessed to do work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

15. Free Energy, Stability, and Equilibrium Free energy measures a system’s instability, or tendency to change to a more stable state In spontaneous changes, free energy decreases and system stability increases Equilibrium is a state of maximum stability A process is spontaneous and can perform work only when it is moving toward equilibrium Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. Fig. 8-5a Less free energy (lower G) More stable Less work capacity More free energy (higher G) Less stable Greater work capacity In a spontaneous change The free energy of the system decreases (∆G < 0) The system becomes more stable The released free energy can be harnessed to do work Fig. 8.5 The relationship of free energy to stability, work capacity, and spontaneous change

17. Fig. 8-5b Spontaneous change Spontaneous change Spontaneous change (b) Diffusion(c) Chemical reaction(a) Gravitational motion Fig 8.5 continued 2. They tend to change spontaneously to a more stable state 1. Unstable systems have a lot of free energy. 3. The energy released can be harnessed to perform work Objects at high positions move lower Molecules in dye disperse Sugar is broken down

18. Free Energy and Metabolism Exergonic and Endergonic Reactions in Metabolism The concept of free energy can be applied to the chemistry of life’s processes Exergonic reactions show a net release of free energy and are spontaneous Endergonic reactions absorb free energy and are not spontaneous Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19. Fig. 8-6a Energy (a) Exergonic reaction: energy released Progress of the reaction Free energy Products Amount of energy released (∆G < 0) Reactants Figure 8.6a Free energy changes (ΔG) in exergonic reactions

20. Fig. 8-6b Energy (b) Endergonic reaction: energy required Progress of the reaction Free energy Products Amount of energy required (∆G > 0) Reactants Figure 8.6b Free energy changes (ΔG) endergonic reactions

21. Equilibrium and Metabolism Reactions in a closed system finally reach equilibrium. No work can be done after that Cells are not in equilibrium; they are open systems experiencing a constant flow of materials & energy A defining feature of life is that metabolism is never at equilibrium A catabolic pathway in a cell releases free energy in a series of reactions Closed and open hydroelectric systems can serve as analogies Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. (a) An isolated hydroelectric system ∆G < 0 ∆G = 0 (b) An open hydro- electric system ∆ G < 0 (c) A multistep open hydroelectric system Fig. 8-7 Figure 8.7 Equilibrium and work in isolated and open systems

23. Concept 8.3: ATP powers cellular work by coupling exergonic 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

24. The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) is the cell’s energy shuttle ATP- made of ribose (sugar), adenine (nitrogen base), and three phosphate groups Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-8 Phosphate groups Ribose Adenine Figure 8.8 The structure of adenosine triphosphate (ATP)

25. Bonds between the phosphate groups of ATP are broken by hydrolysis Energy is released when the terminal phosphate bond is broken This release is due to a chemical change to a lower free energy state, not from the phosphate bonds themselves Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. Fig. 8-9 Inorganic phosphate Energy Adenosine triphosphate (ATP) Adenosine diphosphate (ADP) P P P PP P + + H2OH2O i Figure 8.9 The hydrolysis of ATP The chemical bond between the second & third phosphate groups is broken by the addition of water. The H+ ion is added to one phosphate and the OH- to the other. Energy is released.

27. How ATP Performs Work All three types of cellular work (mechanical, transport, and chemical) are powered by ATP hydrolysis In cells, energy from the exergonic reactions of ATP hydrolysis can be used to drive endergonic reactions Overall, the coupled reactions are exergonic Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

28. Fig. 8-10 (b) Coupled with ATP hydrolysis, an exergonic reaction Ammonia displaces the phosphate group, forming glutamine. (a) Endergonic reaction (c) Overall free-energy change P P Glu NH 3 NH 2 Glu i ADP + P ATP + + Glu ATP phosphorylates glutamic acid, making the amino acid less stable. Glu NH 3 NH 2 Glu + Glutamic acid Glutamine Ammonia ∆G = +3.4 kcal/mol + 2 1 Figure 8.10 How ATP drives chemical work: Energy coupling using ATP hydrolysis

29. ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to another molecule, like a reactant The recipient molecule is now phosphorylated Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

30. Fig. 8-11 (b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed Membrane protein P i ADP + P Solute Solute transported P i VesicleCytoskeletal track Motor protein Protein moved (a) Transport work: ATP phosphorylates transport proteins ATP Figure 8.11 How ATP drives transport and mechanical work

31. The Regeneration of ATP ATP is renewable & is regenerated by adding a phosphate group to adenosine diphosphate (ADP) Energy to phosphorylate ADP comes from catabolic reactions in the cell Chemical potential energy (CPE) stored in ATP drives most cellular work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

32. Fig. 8-12 P i ADP + 1. Energy comes in from the catabolism of food (exergonic, energy-releasing reaction) ATP + H2OH2O Figure 8.12 The ATP cycle (especially in animal cells) 2. The energy released is used in anabolism to add inorganic phosphate (Pi) to ADP making ATP (endergonic, energy using reaction) 3. Water is used to break Pi off of ATP releasing energy in a catabolic, exergonic reaction 4. This energy is now available for cellular work (endergonic, energy-consuming processes)

33. Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers Catalyst- chemical agent that speeds up a reaction without being consumed by it Enzyme- a catalytic protein – Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

34. Fig. 8-13 Sucrose (C 12 H 22 O 11 ) Glucose (C 6 H 12 O 6 ) Fructose (C 6 H 12 O 6 ) Sucrase Figure 8.13 Example of an enzyme- catalyzed reaction: hydrolysis of sucrose by sucrase Sucrase adds water to sucrose in a hydrolysis reaction (catabolic rxn)

35. The Activation Energy Barrier Chemical reactions between molecules require bond breaking & bond forming The energy needed to start a reaction is the free energy of activation, or activation energy (E A ) Activation energy is often supplied as heat from the surroundings Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

36. Fig. 8-14 Progress of the reaction Products Reactants ∆G < O Transition state Free energy EAEA DC BA D D C C B B A A Figure 8.14 Energy profile of an exergonic reaction

37. How Enzymes Lower the E A Barrier Enzymes don’t change the free energy (∆G); instead, they speed up reactions that would occur eventually Enzymes catalyze reactions by lowering the E A barrier Enzymes are never “used up,” they continue to cycle through the reaction until there is no more substrate Animation: How Enzymes Work Animation: How Enzymes Work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

38. Figure 8.15 The effect of an enzyme on activation energy Fig. 8-15 Progress of the reaction Products Reactants ∆G is unaffected by enzyme Course of reaction without enzyme Free energy E A without enzyme E A with enzyme is lower Course of reaction with enzyme

39. Substrate Specificity of Enzymes Substrate- reactant an enzyme binds to Enzyme-substrate complex- forms when an enzyme binds to its substrate Active site- the region on an enzyme where the substrate binds Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

40. Fig. 8-16 Substrate Active site Enzyme Enzyme-substrate complex (b)(a) Figure 8.16 Induced fit between an enzyme and its substrate (demonstrates substrate specificity)

41. Catalysis in the Enzyme’s Active Site In an enzymatic reaction, the substrate binds to the active site of the enzyme The active site can lower an E A barrier by – Orienting substrates correctly – Straining substrate bonds – Providing a favorable microenvironment – Covalently bonding to the substrate Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

42. Fig. 8-17 Substrates Enzyme Products are released. Products Substrates are converted to products. Active site can lower E A and speed up a reaction. Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit). Active site is available for two new substrate molecule s. Enzyme-substrate complex 5 3 2 1 6 4 Figure 8.17 The active site and catalytic cycle of an enzyme

43. Effects of Local Conditions on Enzyme Activity Enzyme activity is affected by – General environmental factors, like temperature and pH – Chemicals that specifically influence the enzyme Effects of Temperature and pH Each enzyme has an – optimal temperature, AND an – optimal pH in which it can function Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

44. Fig. 8-18 Rate of reaction Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Optimal temperature for typical human enzyme (a) Optimal temperature for two enzymes (b) Optimal pH for two enzymes Rate of reaction Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Temperature (ºC) pH 54 3210 678910 0 20 40 80 60100 Figure 8.18 Environmental factors affecting enzyme activity

45. Effect of Cofactors & Enzyme Inhibitors Cofactors- nonprotein enzyme helpers may be – inorganic (such as a metal in ionic form) or – organic Coenzymes are organic cofactors – Vitamins are coenzymes Competitive inhibitors bind to the active site & compete with the substrate Noncompetitive inhibitors bind to another area, making the enzyme change shape; makes the active site less effective Inhibitors include toxins, poisons, pesticides, and antibiotics Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

46. Fig. 8-19 (a) Normal binding (c) Noncompetitive inhibition (b) Competitive inhibition Noncompetitive inhibitor Active site Competitive inhibitor Substrate Enzyme Figure 8.19 Inhibition of enzyme activity

47. Concept 8.5: Regulation of enzyme activity helps control metabolism Cells prevent chemical chaos by regulating all metabolic pathways. Two methods of control: – switching on or off genes coding for specific enzymes – regulating the activity of enzymes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

48. Allosteric Regulation of Enzymes Allosteric regulation inhibits or stimulates enzyme activity Allosteric regulation- regulatory molecule binds to a protein at one site to affect protein function at another (ex. noncompetitive inhibition) Most allosterically regulated enzymes – are made from polypeptide subunits – have active and inactive forms An activator stabilizes the enzyme’s active form An inhibitor stabilizes the enzyme’s inactive form Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

49. Fig. 8-20a (a) Allosteric activators and inhibitors Inhibitor Non- functional active site Stabilized inactive form Inactive form Oscillation Activator Active formStabilized active form Regulatory site (one of four) Allosteric enzyme with four subunits Active site (one of four) Figure 8.20a Allosteric regulation of enzyme activity

50. Cooperativity is an allosteric regulation that amplifies enzyme activity In cooperativity, binding a substrate to an active site stabilizes useful conformational changes to all other subunits Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-20b (b) Cooperativity: another type of allosteric activation Stabilized active form Substrate Inactive form Figure 8.20b Allosteric regulation of enzyme activity

51. Identification of Allosteric Regulators Allosteric regulators are attractive drug candidates for enzyme regulation Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52. Fig. 8-21a SH Substrate Hypothesis: allosteric inhibitor locks enzyme in inactive form Active form can bind substrate S–S SH Active site Caspase 1 Known active form Known inactive form Allosteric binding site Allosteric inhibitor EXPERIMENT Figure 8.21 Are there allosteric inhibitors of caspase enzymes?

53. Fig. 8-21b Caspase 1 RESULTS Active form Inhibitor Allosterically inhibited form Inactive form Figure 8.21 Are there allosteric inhibitors of caspase enzymes?

54. 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

55. Fig. 8-22 Intermediate C Feedback inhibition Isoleucine used up by cell Enzyme 1 (threonine deaminase ) End product (isoleucine) Enzyme 5 Intermediate D Intermediate B Intermediate A Enzyme 4 Enzyme 2 Enzyme 3 Initial substrate (threonine) Threonine in active site Active site available Active site Of enzyme 1 no longer binds threonine; pathway Is switched off. Isoleucine binds to allosteric site Figure 8.22 Feedback inhibition in isoleucine synthesis

56. Specific Localization of Enzymes Within the Cell Structures within the cell help bring order to metabolic pathways Some enzymes act as structural components of membranes In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings