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Introduction to Metabolism

Introduction to Metabolism. Metabolism (The Acquisition and Utilization of Free Energy). Catabolism: exergonic oxidation Anabolism: endergonic processes. Endergonic Processes. Mechanical Work Active Transport Biosynthesis. Anabolism and Catabolism. ATP. NADP +. Niacin. Figure 14-1.

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Introduction to Metabolism

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  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

  5. ATP

  6. NADP+

  7. Niacin Figure 14-1

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

  9. Roles of ATP and NADP+ in Metabolism

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

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

  12. Metabolic Map

  13. Overview of Catabolism Figure 14-3

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

  15. Steady State

  16. Metabolic Functions of Eukaryotic Organelles Table 14-3

  17. Isoenzymes(e.g. lactate dehydrogenase) M-type (muscle) H-type (heart) Use in medical diagnosis – heart attacks release LDH(M) into blood

  18. Potential Futile Cycles(Regulation)

  19. Regulation of Metabolic Pathways Specific Controls General Controls

  20. Specific Controls • Control of Enzyme Amount (153B) • Constitutive Enzymes • Inducible Enzymes • Repressible Enzymes • Control of Enzyme Activity (153A) • Regulatory Enzymes • Effectors (Ligands)

  21. 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!

  22. Types of Reactions

  23. Group Transfer Reactions

  24. Phosphoryl Group Transfer

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

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

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

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

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

  30. One Electron Oxidation-Reduction Reactions

  31. Half-Reactions

  32. Alcohol Dehydrogenase(Oxidation-Reduction Reaction)

  33. Elimination Reactions

  34. Isomerization Reactions(Intramolecular Hydrogen Shifts)

  35. Racemization and Epimerization Racemization: change stereochemistry of only chiral center Epimerization: change stereochemistry of one chiral center of molecule with more than one chiral centers

  36. Rearrangements(altered carbon skeletons)

  37. Making C-C Bonds Note: thioester

  38. Breaking C-C Bonds

  39. Experimental Approachesto Metabolism

  40. Features of Metabolic Pathways A ——> B ——> C ——> D ——> E Sequences and Energetics Enzymes and Mechanisms Control Mechanisms (Regulation) Compartmentation

  41. Elucidation of Metabolic Pathways A ——> B ——> C ——> D ——> E Metabolic Inhibitors: accumulation of intermediates Biochemical Genetics: mutants Pathway Labeling: isotopes

  42. Metabolic Inhibitors(Accumulation of Intermediates)(e.g. Glycolysis) Iodoacetate: fructose-1,6-bisphosphate Fluoride: 3-phosphoglycerate and 2–phosphoglycerate

  43. Biochemical Genetics(Mutants) Natural Genetic Defects Manipulation of Microorganisms A ——> B ——> C ——> D ——> E Accumulation of Intermediates Growth Requirements (auxotrophic mutants)

  44. Pathway Labeling A* ——> B* ——> C* Stable Isotopes Radioisotopes

  45. Detection of Isotopes • Stable Isotopes • Mass Spectrometry • NMR • Radioisotopes • Proportional Counting (Geiger Counter) • Liquid Scintillation Counting • Autoradiography

  46. Enzymes and Mechanisms Biochemistry

  47. Control Mechanisms (Regulation) Molecular Biology Biochemistry

  48. Compartmentation(Isolated Organs/Tissues, Cells and Subcellular Organelles) Cell Biology Biochemistry

  49. ATP Kinetic StabilityofPhosphoanhydride Bonds

  50. ATP Phosphoester Bonds: acid and alcohol Phosphoanhydride Bonds: two acids

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