Introduction to Metabolism: The Energy of Life

1. Chapter 8 An Introduction to Metabolism

2. Figure 8.1 Overview: The Energy of Life • The living cell • Is a miniature factory where thousands of reactions occur • Converts energy in many ways

3. 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

4. Metabolic Pathways • Catabolic pathways • Break down complex molecules into simpler compounds • Release energy • Anabolic pathways • Build complicated molecules from simpler ones • Consume energy

5. 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 Forms Of Energy • Energy can be converted • From one form to another

6. 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  First Law Of Thermodynamics • An example of energy conversion

7. 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 • According to the second law of thermodynamics • Spontaneous changes that do not require outside energy increase the entropy, or disorder, of the universe

8. 50µm Figure 8.4 Biological Order and Disorder • Living systems • Increase the entropy of the universe • Use energy to maintain order

9. Free-Energy Change, G • A living system’s free energy • Is energy that can do work under cellular conditions • 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

10. More free energy (higher G) • Less stable • Greater work capacity • In a spontaneously 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 . • Less free energy (lower G) • More stable • Less work capacity (a) Gravitational motion. Objects move spontaneously from a higher altitude to a lower one. (c) (b) Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed. Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. Figure 8.5  • At maximum stability • The system is at equilibrium

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

12. Products Amount of energy released (∆G>0) Free energy Energy Reactants Progress of the reaction Figure 8.6 (b) Endergonic reaction: energy required Endergonic Reaction in Metabolism • An endergonic reaction • Is one that absorbs free energy from its surroundings and is nonspontaneous

13. ∆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

14. (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 • Experience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibrium

15. ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucoce is brocken 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

16. 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

17. 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

18. 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 by ATP • ATP hydrolysis • Can be coupled to other reactions

19. P i P Motor protein Protein moved (a) Mechanical work: ATP phosphorylates motor proteins Membrane protein ADP + ATP P i P P i Solute Solute transported (b) Transport work: ATP phosphorylates transport proteins P NH2 + + NH3 P i Glu Glu Reactants: Glutamic acid and ammonia Product (glutamine) made Figure 8.11 (c) Chemical work: ATP phosphorylates key reactants Type Of ATP Energy Coupled Reaction • The three types of cellular work • Are powered by the hydrolysis of ATP

20. 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

21. 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 Functions Of Enzymes • The hydrolysis • Is an example of a chemical reaction

22. A B D C Transition state B A EA D C Free energy Reactants B A ∆G < O C D Products Progress of the reaction Figure 8.14 Activation Energy • The energy profile for an exergonic reaction

23. 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 Role Of An Enzyme • The effect of enzymes on reaction rate

24. Substrate Specificity of Enzymes • The substrate • Is the reactant an enzyme acts on • The enzyme • Binds to its substrate, forming an enzyme-substrate complex

25. Substate Active site Enzyme- substrate complex (b) Enzyme Figure 8.16 (a) Figure 8.16 Substrate Specificity of Enzymes • Induced fit of a substrate • Brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction

26. 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA 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 Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. 4 Substrates are Converted into Products. Figure 8.17 Products The catalytic cycle of an enzyme

27. Mechanisms For Lowering Activation Energy • The active site can lower an EA barrier by • Orienting substrates correctly • Straining substrate bonds • Providing a favorable microenvironment • Covalently bonding to the substrate

28. 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 • Each enzyme • Has an optimal temperature in which it can function

29. 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 Effects of pH • Has an optimal pH in which it can function

30. 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

31. 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 • Bind to another part of an enzyme, changing the function

32. Allosteric activaterstabilizes active from Allosteric enyzmewith four subunits Active site(one of four) Regulatorysite (oneof four) Activator Active form Stabilized active form Allosteric activaterstabilizes active form Oscillation Non-functionalactivesite Inhibitor Stabilized inactiveform Inactive form (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Figure 8.20 Enzyme Regulation • They change shape when regulatory molecules bind to specific sites, affecting function

33. Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation. Substrate Inactive form Stabilized active form (b)Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate. Figure 8.20 • Cooperativity • Is a form of allosteric regulation that can amplify enzyme activity

34. 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 • Feedback inhibition

35. Mitochondria, sites of cellular respiraion Figure 8.22 1 µm Specific Localization of Enzymes Within the Cell • Within the cell, enzymes may be • Grouped into complexes • Incorporated into membranes