Chapter 8: An Introduction to Metabolism

1. Chapter 8:An Introductionto Metabolism

2. Important Point: If you are having trouble understanding lecture material: Try reading your text before attending lectures. And take the time to read it well!

3. Metabolism = Catabolism + Anabolism • Catabolic reactions are energy yielding • They are involved in the breakdown of more-complex molecules into simpler ones • Anabolic reactions are energy requiring • They are involved in the building up of simpler molecules into more-complex ones • We can consider these bioenergetics in terms of the physical laws of thermodynamics Metabolism (Overview)

4. 1st & 2nd Laws of Thermodynamics “Every energy transfer or transformation increases the disorder (entropy) of the universe.” p. 143, Campbell & Reece (2005) Note especially the waste heat “Energy can be transferred or transformed but neither created nor destroyed.” p. 143, Campbell & Reece (2005)

5. Organisms take in energy & transduce it to new forms (1st law) • As energy transducers, organisms are less than 100% efficient (2nd law) • Organisms employ this energy to: • Grow • Protect Themselves • Repair Themselves • Compete with other Organisms • Make new Organisms (I.e., babies) • In the process, organisms generate waste chemicals & heat • Organisms create local regions of order at the expense of the total energy found in the Universe!!! We are Energy Parasites! Organisms are Energy Transducers

6. Water “Fall” Analogy Get it?

7. First Law of Thermodynamics: • Energy can be neither created nor destroyed • Therefore, energy “generated” in any system is energy that has been transformed from one state to another (e.g., chemically stored energy transformed to heat) • Second Law of Thermodynamics: • Efficiencies of energy transformation never equal 100% • Therefore, all processes loseenergy, typically as heat, and are not reversible unless the system is open & the lost energy is resupplied from the environment • Conversion to heat is the ultimate fate of chemical energy Laws of Thermodynamics

8. Increase stability Downhill Movements Toward Equilibrium G < 0 Greater entropy

9. Entropy!

10. Free Energy & Spontaneity What is the name of this molecule?

11. Movement Toward Equilibrium Work Equilibrium Potential energy Spontaneous Forward reaction

12. Movement Toward Equilibrium Viable organisms exist in a chemical disequilibrium that is maintained via the harnessing of energy obtained from the organism’s environment (e.g., you eat to live)

13. Gravity (center Earth) Potential Energy Waterfall Analogy Really… Kinetic Energy Stayring of a turbine generator, Priest Rapids Dam, 1958 Waste Heat (once reaches Bottom)

14. “Food” Spontaneous Movement Toward Equilibrium Potential energy Waste heat Forward reaction Work

15. Movement Toward Equilibrium in Steps Note that “Spontaneity” is not a measure of speed of a process, only its direction

16. Exergonic Reactions “Food” Energy released Movement toward equilibrium

17. Endergonic Reactions “Work” Energy required

18. Exergonic Reaction (Spontaneous) • Decrease inGibbs free energy (-G) • Increase in stability • Spontaneous (gives off net energy upon going forward) • Downhill (toward center of gravity well, e.g., of Earth) • Movement towards equilibrium • Coupled to ATP production (ADP phosphorylation) • Catabolism Endergonic Rxn (Non-Spontaneous) • Increase inGibbs free energy (+G) • Decrease in stability • Not Spontaneous (requires net input of energy to go forward) • Uphill (away from center of gravity well, e.g., of Earth) • Movement away from equilibrium • Coupled to ATP utilization (ATP dephosphorylation) • Anabolism

19. Minus the cut for the 2nd law Coupling Reactions Exergonic reactions can supply energy for endergonic reactions

20. Catabolic reactions provide the energy that drives anabolic reactions forward Energy Coupling in Metabolism Catabolic reaction Anabolic reaction

21. Adenosine Triphosphate (ATP) Call this “A”

22. Energy Coupling via ATP

23. Hydrolysis of ATP Movement toward equilibrium

24. Coupled Reactions

25. How that reaction really works…

26. Various Pi Transfers

27. Summary of Metabolic Coupling Exergonic reaction Endergonic reaction Exergonic reaction Endergonic reaction Get it? Exergonic processes drive Endergonic processes

28. “Food” Endergonic Movement Toward Equilibrium Exergonic

29. Coupling the Biosphere Anabolic process Catabolic process Chemically stored energy

30. Enzyme Catalyzed Reaction Question: Is this reaction endergonic or is it exergonic? Enzyme

31. Anything that doesn’t require an input of energy to get started has already happened! Activation Energy (EA)

32. Why don't energy-rich molecules, e.g., glucose, spontaneously degrade into CO2 and Water? • To be unstable, something must have the potential to change into something else, typically something that possesses less free energy (e.g., rocks) • To be unstable, releasing something’s ability to change into something else must also be relatively easy (i.e., little input energy) • Therefore, stability = already low free energy • Alternatively, stability = high activation energy • Things, therefore, can be high in free energy but still quite stable, e.g., glucose Low- (i.e., body-) Temp. Stability

33. Catalysis Lowering of activation energy

34. Catalysis This is instead of adding heat; heat is an inefficient means of speeding up reactions since it simply is a means of increasing the random jostlings of molecules At a given temperature, catalyzed reactions can run faster because less energy is required to achieve the transition state

35. Enzyme-mediated Catalysis = Subtle application of energy

36. Active sites can hold two or more substrates in proper orientations so that new bonds between substrates can form • Active sites can stress the substrate into the transition state • Active sites can maintain conducive physical environments (e.g., pH) • Active sites can participate directly in the reaction (e.g., forming transient covalent bonds with substrates) • Active sites can carry out a sequence of manipulations in a defined temporal order (e.g., step A  step B  step C) Mechanisms of Catalysis

37. Catalysis as Viewed in 3D The rest of an enzyme is involved in supporting active site, controlling reaction rates, attaching to other things, etc. Active site is site of catalysis

38. Induced Fit (Active Site) Induced fit not only allows the enzyme to bind the substrate(s), but also provides a subtle application of energy (e.g., “bending” chemical bonds) that causes the substrate(s) to destabilize into the transition state

39. Product Substrate Enzyme Saturation Enzyme Activity at Saturation is a Function of Enzyme Turnover Rate

40. Enzyme Saturation Turnover rate

41. Non-Specific Inhibition of Enzyme Activity Reduced rate of chemical reaction Instability & shape change (too fluid) Reduced enzyme fluidity Denatured? Turnover rate Change in R group ionization Change in R group ionization Even at saturation, rates of enzymatic reactions can be modified

42. Metal Ion or = Organic Molecule = Organic Cofactor Polypeptide Activators of Catalysis Don’t worry about “apoenzyme” and “holoenzyme”

43. Competitive inhibitors can be competed off by supplying sufficient substrate densities Specific Inhibition Non-competitive inhibitors cannot be competed off by substrate

44. Reversible interactions, sometimes on, sometimes off, dependent on binding constant and density of effector Allosteric Interactions

45. Cooperativity Cooperativity is when the activity of other subunits are increased by substrate binding to one subunit’s active site

46. Feedback Inhibition

47. Energy-Metabolism Regulation

48. Organization of Electron Transport Chain of Cellular Respiration: Substrate  Enzyme  Product  Enzyme chains are co-localized Enzyme Localization Enzymes in single pathway may be co-localized so that the product of one enzyme increases the local concentration of the substrate for another

49. The End