Chapter 8

1. Chapter 8 An Introduction to Metabolism

2. Overview: The Energy of Life • The living cell • Is a miniature factory where thousands of reactions occur • Converts energy in many ways

3. Figure 8.1 • Some organisms • Convert energy to light, as in bioluminescence

4. Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics

5. Metabolism • Is the totality of an organism’s chemical reactions • Arises from interactions between molecules • Catabolic pathways • Break down complex molecules into simpler compounds • Release energy • Anabolic pathways • Build complicated molecules from simpler ones • Consume energy

6. Enzyme 1 Enzyme 2 Enzyme 3 A D C B Reaction 1 Reaction 2 Reaction 3 Startingmolecule Product Organization of the Chemistry of Life into Metabolic Pathways • A metabolic pathway has many steps • That begin with a specific molecule and end with a product • That are each catalyzed by a specific enzyme

7. Forms of Energy • Energy • Is the capacity to cause change • Exists in various forms, of which some can perform work Radiant/light Thermal/Heat Electrical Mechanical (kinetic) Chemical Nuclear

8. Kinetic energy • Is the energy associated with motion • Potential energy • Is stored in the location of matter • Includes chemical energy stored in molecular structure

9. On the platform, a 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, a diver has less potential energy. Figure 8.2 • Energy can be converted • From one form to another

10. The Laws of Energy Transformation • Thermodynamics • Is the study of energy transformations

11. Chemical energy (a) First law of thermodynamics: Energy can be transferred or transformed but Neither created nor destroyed. For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement in (b). Figure 8.3  The First Law of Thermodynamics • According to the first law of thermodynamics, • Energy can be changed from one form to another, but it cannot be created or destroyed. Implication: The total amount of energy and matter in the Universe remains constant, merely changing from one form to another.

12. The Second Law of Thermodynamics • In all energy exchanges, if no energy enters or leaves the system, the potential energy of the state will always be less than that of the initial state." • This is also commonly referred to as entropy. • Examples: • A watchspring-driven watch will run until the potential energy in the spring is converted, and not again until energy is reapplied to the spring to rewind it. • A car that has run out of gas will not run again until you walk 10 miles to a gas station and refuel the car. • Once the potential energy locked in carbohydrates is converted into kinetic energy (energy in use or motion), the organism will get no more until energy is input again.

13. Biological Order and Disorder • Living systems increase the entropy (S) of the universe • Energy must be input to maintain order

14. Heat co2 + H2O Second law of thermodynamics: Every energy transfer or transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings in the form of heat and the small molecules that are the by-products of metabolism. (b) Figure 8.3  The Second Law of Thermodynamics • Energy IN = Energy OUT + dissipates • In the process of energy transfer, some energy will dissipate as heat. Term: dissipates = “lost” energy (ex: body heat). No longer ‘available’ to do work

15. Entropy • Entropy is a measure of disorder: cells are NOT disordered and so have low entropy. • The flow of energy maintains order and life. • Entropy wins when organisms cease to take in energy and die.

16. Free-Energy Change, G • A living system’s free energy • Is energy that can do work under cellular conditions • The free-energy change of a reaction tells us whether the reaction occurs spontaneously

17. The change in free energy, ∆Gduring a biological process • Is related directly to the enthalpy change (∆H) and the change in entropy • ∆G = ∆H – T∆S In chemical reactions, the total enthalpy (H) is the amount of energy stored in all of the bonds; that is, the amount of energy it would require to break all of the bonds. Generally this is expressed as heat-releasing (exothermic) or heat-absorbing (endothermic)

18. Free Energy, Stability, and Equilibrium • Organisms live at the expense of free energy • During a spontaneous change • Free energy decreases and the stability of a system increases If the amount of energy released from breaking bonds is more than the energy required to make bonds, then overall, the reaction will release energy. = negative free energy change (exergonic) - ∆G

19. Reactants Amount of energy released (∆G <0) Free energy Energy Products Progress of the reaction Figure 8.6 (a) Exergonic reaction: energy released Exergonic Reactions in Metabolism • An exergonic reaction (- ∆G ) • Proceeds with a net release of free energy and is spontaneous

20. Products Amount of energy released (∆G>0) Free energy Energy Reactants Progress of the reaction Figure 8.6 (b) Endergonic reaction: energy required Endergonic Reactions in Metabolism • An endergonic reaction (+ ∆G ) • Is one that absorbs free energy from its surroundings and is non spontaneous (requires energy input)

21. ∆G < 0 ∆G = 0 (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. Figure 8.7 A Equilibrium and Metabolism • Reactions in a closed system • Eventually reach equilibrium

22. (b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium. ∆G < 0 Figure 8.7 • Cells in our body exist in an OPEN system • Experience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibrium • A cell does three main kinds of work: • Mechanical • Transport • Chemical

23. Coupling reactions • Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions In other words, in a series of linked reactions, the steps that have -∆G (exergonic) can “pull” along those steps that require energy (endergonic, +∆G )

24. ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucose is broken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium. Figure 8.7 • An analogy for cellular respiration, a biochemical pathway of linked chemical reactions

25. Energy coupling Is a key feature in the way cells manage their energy resources to do this work In other words, in a series of linked reactions, the steps that have -∆G (exergonic) can “pull” along those steps that require energy (endergonic, +∆G )

26. Adenine NH2 C N C N HC O O O CH C N - N O O O O CH2 O - - - O O O H H Phosphate groups H H Ribose Figure 8.8 OH OH The Structure and Hydrolysis of ATP • ATP (adenosine triphosphate) • Is the cell’s energy shuttle • Provides energy for cellular functions

27. P P P Adenosine triphosphate (ATP) H2O Energy + P i P P Adenosine diphosphate (ADP) Inorganic phosphate Figure 8.9 • Energy is released from ATP • When the terminal phosphate bond is broken

28. Endergonic reaction: ∆G is positive, reaction is not spontaneous NH2 NH3 + ∆G = +3.4 kcal/mol Glu Glu Glutamine Glutamic acid Ammonia Exergonic reaction: ∆ G is negative, reaction is spontaneous ∆G = - 7.3 kcal/mol + P ADP H2O ATP + Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol Figure 8.10 Energy coupling • Can be coupled to other reactions

29. How ATP Performs Work • ATP drives endergonic reactions • By phosphorylation, transferring a phosphate to other molecules

30. ATP hydrolysis to ADP + P i yields energy ATP synthesis from ADP + P i requires energy ATP Energy from catabolism (exergonic, energy yielding processes) Energy for cellular work (endergonic, energy- consuming processes) ADP + P i Figure 8.12 The Regeneration of ATP • Catabolic pathways • Drive the regeneration of ATP from ADP and phosphate

31. The Role of Enzymes in Energetics • Enzymes speed up metabolic reactions by lowering energy barriers • A catalyst • Is a chemical agent that speeds up a reaction without being consumed by the reaction • An enzyme • Is a catalytic protein

32. CH2OH CH2OH CH2OH CH2OH O O O O H H H H H H H Sucrase H OH H HO OH H HO H2O O + H H OH O HO CH2OH CH2OH OH H H H OH H OH OH Fructose Glucose Sucrose Figure 8.13 C12H22O11 C6H12O6 C6H12O6 The Activation Barrier • Every chemical reaction between molecules • Involves both bond breaking and forming bonds. • The hydrolysis of a disaccharide is an example:

33. Chemical Reactions • The activation energy, EA • Is the initial amount of energy needed to start a chemical reaction • Is often supplied in the form of heat from the surroundings in a system

34. Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants Free energy ∆G is unaffected by enzyme Course of reaction with enzyme Products Progress of the reaction Figure 8.15 The effect of enzymes on reaction rate • An enzyme catalyzes reactions • By lowering the EA barrier

35. Substrate Specificity of Enzymes • The substrate (A) • Is the reactant an enzyme acts on • The enzyme • Binds to its substrate, forming an enzyme-substrate complex (C)

36. The active site • Is the region on the enzyme where the substrate binds • Their shape (conformation) makes each enzyme substrate-specific • “Lock-and-key” fit enables reaction

37. The active site can lower an EA barrier by • Orienting substrates correctly • Straining substrate bonds • Providing a favorable microenvironment • Covalently bonding to the substrate

38. Effects of Local Conditions on Enzyme Activity • The activity of an enzyme • Is affected by general environmental factors • temperature • pH • salinity • enzyme concentration • substrate concentration • presence of any inhibitors or activators.

39. Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent (e.g., alcohol or chloroform), or heat. • If proteins in a living cell are denatured, this results in disruption of cell activity and possibly cell death.

40. Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Rate of reaction 80 0 20 100 40 Temperature (Cº) (a) Optimal temperature for two enzymes Figure 8.18 Effects of Temperature and pH • Each enzyme • Has an optimal temperature in which it can function

41. Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Rate of reaction 5 6 7 8 9 3 4 0 2 1 (b) Optimal pH for two enzymes Figure 8.18 • Has an optimal pH in which it can function

42. Cofactors & Coenzymes • Cofactors • Are nonprotein enzyme helpers • Most often minerals (metal ions) • Zn 2+, Mg2+ • Coenzymes • Are organic cofactors • Usually vitamins • B2, B6, B12, etc

43. Enzyme 1 Enzyme 2 Enzyme 3 A D C B Reaction 1 Reaction 2 Reaction 3 Startingmolecule Product Enzymes Regulate reactions • Concept 8.5: Regulation of enzyme activity helps control metabolism • A cell’s metabolic pathways • Must be tightly regulated

44. Allosteric Activation and Inhibition • Many enzymes are allosterically regulated • Allosteric regulation • Is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site • Enzymes can be “turned on” or “turned off” this way

45. A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor Figure 8.19 (b) Competitive inhibition Enzyme Inhibitors • Competitive inhibitors • Bind to the active site of an enzyme, competing with the substrate

46. 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. Noncompetitive inhibitor (c) Noncompetitive inhibition Figure 8.19 Noncompetitive inhibitors • Noncompetitive inhibitors • Bind to another part of an enzyme, changing the function

47. Initial substrate(threonine) Active siteavailable Threoninein active site Enzyme 1(threoninedeaminase) Isoleucineused up bycell Intermediate A Feedbackinhibition Active site of enzyme 1 no longer binds threonine;pathway is switched off Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site Enzyme 4 Intermediate D Enzyme 5 Figure 8.21 End product(isoleucine) Feedback inhibition • In feedback inhibition • The end product of a metabolic pathway shuts down the pathway

48. Mitochondria, sites of cellular respiraion Figure 8.22 1 µm • Eukaryotic cells improve effectiveness by “compartmentalizing” their enzymatic processes • Contained inside organelles