Introduction to Metabolism

1. Introduction to Metabolism

2. Metabolism(The Acquisition and Utilization of Free Energy) Catabolism: exergonic oxidation Anabolism: endergonic processes

3. Endergonic Processes • Mechanical Work • Active Transport • Biosynthesis

4. Anabolism and Catabolism exergonic endergonic

5. Roles of ATP and NADP+ in Metabolism

6. ATP Kinetic StabilityofPhosphoanhydride Bonds

7. ATP Triphosphate Adenosine Ribose

8. Hydrolysis of ATP

9. Phosphate Compounds

10. Roles of ATP(Coupled Reactions) ∆Go’ (kJ/mol) ---------- Fructose-6-P + Pi ——> Fructose-1,6-bisP + H2O +13.3 ATP + H2O ——> ADP + Pi -30.5 ------------------------------------------------------------------------------- Fructose-6-P + ATP ——> Fructose-1,6-bisP + ADP -17.2

11. Roles of ATP • Early stages of nutrient breakdown Glucose + ATP ——> Glucose-6-P + ADP • Interconverson of nucleoside triphosphtes NDP + ATP ——> NTP + ADP Nucleoside Diphosphate Kinase • Physiological processes • Muscle contraction • Active transport

12. Roles of ATP • Additional phosphoanhydride cleavages in highly endergonic reactons (NMP)n + NTP ——> (NMP)n+1 + PPi PPi + H2O ——> 2 Pi Pyrophosphatase

13. Sources of ATP Phototrophs: photosynthesis Chemotrophs: oxidation of organic compounds (e.g. carbohydrates, lipids, and proteins)

14. Formation of ATP • Adenylate Kinase reaction2 ADP ——> AMP + ATP • Substrate-level phosphorylationX–P + ADP ——> X–H + ATP • Oxidative phosphorylation • Photophosphorylation

15. Substrate-Level Phosphorylation

16. Oxidative Phosphorylation

17. Photophosphorylation

18. Source of NAD(P)+, and other cofactors

19. Source of NAD(P)+, and other cofactors

20. NADP+Nicotinamide Adenine Dinucleotide (Phosphate)

21. Niacin Figure 14-1

22. Reduction of NAD+ or NADP+ to NADH or NADPH Figure 14-11

23. Metabolic Pathways A ——> B ——> C ——> D ——> E Metabolites Enzymes

24. Metabolic Map

26. Overview of Catabolism Figure 14-3

27. Properties of Metabolic Pathways • Separate Anabolic and Catabolic Pathways • Steady-State • Irreversible (overall): reversibility of individual steps • First Committed (Exergonic) Step: others close to equilibrium • Compartmentation (organelles & tissues): isoenzymes and transport • Regulation (usually first committed step): often rate-limiting

28. Potential Futile Cycles(Regulation)

29. Steady State

30. Thermodynamics of individual steps A  B Go’ = -RTlnKeq Not standard conditions or at equilibrium: G = Go’+RTln([B]/[A]) Three Physiological Conditions: Go’<<<<<<0 : G always negative Example: ATP hydrolysis Go’>0 : near equilibrium, reversible, direction depends on actual [B]/[A] Example: Most reactions Go’>>>>>>0 : G always positive, must be coupled Example: Phosphorylation of Glucose

31. Go’>0 Go’>0 Go’>0 Go’>0 Go’>0 Go’>0

32. Go’>0 Go’>0 Go’>0 Go’>0 Go’>0 Go’>0

33. Regulation of Metabolic Pathways Specific Controls General Controls

34. Specific Controls • Control of Enzyme Amount • Constitutive Enzymes • Inducible Enzymes • Repressible Enzymes • Control of Enzyme Activity • Regulatory Enzymes • Effectors (Ligands)

35. General Controls(Integration of Cellular or Organism Functions) • Internal Effectors • Catabolite Repression • Energy Charge • Reduction Potential • External Effectors (e.g. hormones) Significance: Efficiency and Flexibility!

36. Types of Reactions

37. Group Transfer Reactions

38. Phosphoryl Group Transfer

39. Elimination Reactions

40. Isomerization Reactions(Intramolecular Hydrogen Shifts)

41. Making C-C Bonds Note: thioester

42. Breaking C-C Bonds

43. Oxidation-Reduction Reactions SH2 + NAD+ + H2O ——> S + NADH + H3O+ SH2: Reduced Substrate S: Oxidized Product NAD+: Electron Acceptor FAD: Electron Acceptor

44. Reduction of NAD+ to NADH Figure 14-11

45. Flavin Adenine Dinucleotide (FAD) Figure 14-12

46. Reduction of FAD to FADH2 Figure 14-13 part 1

47. Reduction of FAD to FADH2 Figure 14-13 part 2

48. One Electron Oxidation-Reduction Reactions

49. Half-Reactions Oxidation Involves (e- of H:-) Loss Reduction Involves (e- of H:-) Gain

50. Alcohol Dehydrogenase(Oxidation-Reduction Reaction)