1. Metabolic Processes Enzymes, Energy and Chemical Reactions

2. Cellular Energy Processing Metabolism: the sum of all chemical reactions –Anabolism: assembly, polymerization, etc. requires energy –Catabolism: disassembly, depolymerization releases energy –some reactions couple anabolism with catabolism –catabolism drives all anabolism –all reactions depend on enzyme catalysts

3. Energy can be stored or used for work Figure 6.1

4. Cellular Energy Processing cellular processes change chemical structures & transport materials –change and movement require energy exchanges –energy exchanges have to follow the law(s)

5. Cellular Energy Processing First Law of Thermodynamics –during any event, Initial Energy = Final Energy

6. …neither created nor destroyed Figure 6.2

7. Cellular Energy Processing First Law of Thermodynamics –during any event, Initial Energy = Final Energy Second Law of Thermodynamics –during any event, some energy is unavailable to do work

8. …some is unusable; disorder increases Figure 6.2

9. Cellular Energy Processing cells obtain energy from outside sources

10. …an external source is required Figure 6.2

11. Total energy = Figure 6.2

12. Cellular Energy Processing  total energy = usable energy + unusable energy, or  enthalpy = free energy + (entropy · absolute temperature)  H=G +TS, so, G=H-TS (three unmeasurable variables)   G=  H-T  S (change in free energy at constant temperature)

13.  G > 0; energy required Figure 6.3

14. Cellular Energy Processing   G=  H-T  S describes energy changes in chemical reactions  positive  G describes an energy-requiring reaction; anabolism; decrease in entropy  negative  G describes an energy-yielding reaction; catabolism; increase in entropy

15.  G < 0; energy released Figure 6.3

16. Cellular Energy Processing  spontaneity (≠ rate)  a spontaneous reaction goes more than half way to completion without an energy input; it is exergonic;  G < 0  a nonspontaneous reaction goes less than half way to completion without an energy input; it is endergonic;  G > 0  if A=>B is exergonic, B=>A is endergonic

17. Cellular Energy Processing  reactions are reversible  A B  add more A, increase => rate  add more B, increase <= rate  equilibrium occurs when rates are equal  the closer to completion equilibrium occurs, the more free energy is released

18. reversible reaction at equilibrium Figure 6.4

19. ATP: the cell’s chief energy currency Figure 6.5

20. cellular respiration supplies ATP for anabolism Figure 6.6

21. ATP hydrolysis coupled to glutamine synthesis Figure 6.7

22. cellular energy transfer  Adenosine TriPhosphate (ATP) is the predominant energy currency in the cell  ATP hydrolysis is exergonic (  G = -7.3 kcal/mol)  ATP + H 2 O => ADP + P i  ATP synthesis is endergonic  ATP shuttles energy from exergonic reactions to endergonic reactions  each ATP is recycled ~10,000 times/day  ~1,000,000 ATPs are used by a cell/second

23. Enzymes: Biological Catalysts  a catalyst: increases the reaction rate; is unchanged by the reaction  most biological catalysts are proteins  some (few) biological catalysts are ribozymes (RNA)

24. E a determines the likelihood that a reaction will occur Figure 6.8

25. Enzymes: Biological Catalysts  each chemical reaction must overcome an energy barrier - activation energy (E a )  spontaneous reactions will go - eventually  the direction is predictable  neither likelihood, nor rate is predictable

26. heat may supply E a Figure 6.9supply

27. E + S => E-S complex => E + P Figure 6.10

28. position substrates Figure 6.12 induce strain alter surface charge

29. Enzymes: Biological Catalysts  how to overcome the energy barrier?  increase kinetic energy of reactant molecules, or  decrease E a  an enzyme binds a specific substrate molecule(s) at its active site  E + S => E-S complex => E + P  the active site > positions reactants, strains bonds, etc. to destabilize the reactants…  …lowering E a

30. enzyme: lowers E a, doesn’t change  G Figure 6.11

31. Enzymes: Biological Catalysts  enzymes…  efficiency experts of the metabolic world  lower activation energy  do not alter equilibrium  increase the rates of forward and reverse reactions

32. Enzymes: Biological Catalysts  substrate concentration affects reaction rate  as increased [reactant] increases reaction rate  so increased [substrate] increases reaction rate  until…  all active sites are occupied  the reaction is saturated

33. enzymatic reactions may be saturated Figure 6.16

34. induced fit in hexokinase Figure 6.14

35. Enzymes: Biological Catalysts  enzyme structure determines enzyme function  the active site fits the substrate  “lock & key”  “induced fit”  the rest of the enzyme  stabilizes the active site  provides flexibility

36. Figure 6.15

37. Enzymes: Biological Catalysts  enzyme structure determines enzyme function  some enzymes require non-protein groups  cofators: reversibly-bound ions  coenzymes: reversibly bound organic molecules  prosthetic groups: permanently bound groups

38. Table 6.1

39. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  sequential reactions form pathways  product of 1 st reaction is substrate for 2 nd E 1 E 2 E 3 E 4 A=> B=> C=> D=> product of pathway  regulation of enzymes in the pathway regulates the entire pathway

40. related to Sarin gas and malathion irreversible inhibition by DIPF Figure 6.17

41. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  enzyme inhibitors provide negative control  artificial inhibitors can be pesticides  irreversible inhibition - covalent modification of active site  natural metabolic regulation is often reversible  competitive inhibition

42. cartoon version Figure 6.18

43. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  enzyme inhibitors provide negative control  artificial inhibitors can be pesticides  irreversible inhibition - covalent modification of active site  natural metabolic regulation is often reversible  competitive inhibition  noncompetitive inhibition

44. cartoon version Figure 6.18

45. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  allosteric enzymes have catalytic and regulatory subunits  active and inactive enzyme conformations are in equilibrium

46. Figure 6.19

47. Figure 6.20

48. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  allosteric enzymes regulate many metabolic pathways  catalyze first committed step  respond sensitively to inhibition  often inhibited by pathway end product - “end-product inhibition”

49. end-product inhibition by isoleucine Figure 6.21

50. Enzymes & Metabolism  metabolic regulation coordinates the many potential enzymatic reactions  allosteric enzymes regulate many metabolic pathways  catalyze first committed step  respond sensitively to inhibition  often inhibited by pathway end product - “end-product inhibition”  saves resources when end product is sufficient

51. secondary & tertiary structures depend onare disrupted by H-bondsheat ionic interactionspH changes hydrophobic interactionsdetergents disulfide bondsred/ox changes

52. pH optima for three enzymes Figure 6.22

53. temperature optimum Figure 6.23

54. Enzymes & Metabolism  enzyme activity relies on proper environmental conditions  some enzymes have isozymes suited to different environmental conditions