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Citric Acid/TCA Cycle

CHAPTER 15: Basic Concepts and Design in Metabolism. Glycolysis Coupled with Cellular Respiration Maximizes Energy Generation. Citric Acid/TCA Cycle. Why are these coupled pathways so important?. Transit and Metabolic Maps: Complex and Functional.

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Citric Acid/TCA Cycle

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  1. CHAPTER 15: Basic Concepts and Design in Metabolism Glycolysis Coupled with Cellular Respiration Maximizes Energy Generation Citric Acid/TCA Cycle Why are these coupled pathways so important?

  2. Transit and Metabolic Maps: Complex and Functional

  3. Carbon Oxidation is Coupled with Energy Rich Reduction Which molecule is more energy rich on a per carbon basis?

  4. Free-Energy Universal-Currency: ATP ATP hydrolysis is exergonic ATP + H2O ADP + Pi ∆G°ʹ = - 30 kJ/mol ATP hydrolysis drives metabolism in heterotrophs Light energy is trapped as ATP in phototrophs Why is ATP an excellent energy currency?

  5. ATP: High Phosphoryl-Transfer Potential • ATP and hydrolysis products differences: • Electrostatic repulsion • Resonance stabilization • Hydration stabilization How can an energetically unfavorable reaction be made spontaneous?

  6. Substrate-Level ATP Phosphoryation Requires High Phosphoryl-Transfer Potential Standard Free Energy of Hydrolysis

  7. ATP: Phosphoryl-Transfer Hub

  8. Duration of Alternative Energy Sources Anaerobic SystemsAerobic Systems ATP: tennis serve Oxidative phosphorylation: Creatine phosphate: sprint race > 500 m Glycolysis: 200 m dash

  9. ATP: A Multifunctional Metabolite High turnover (ca. 90 lbs/24 hrs)

  10. Additional Activated Carriers Nicotinamide Adenine Dinucleotide (NAD+) Electron carriers in oxidation-reduction reactions NADH functions in catabolism NADPH functions in anabolism Nicotinamide Adenine Dinucleotide Phosphate (NADP+)

  11. Additional Activated Carriers Electron carriers in oxidation-reduction reactions FADH functions in both catabolism and anabolism Flavin adenine dinucleotide (FAD)

  12. Substrate Specificity for Dinucleotide Oxidation-Reduction Reactions

  13. Fatty Acid Biosynthesis via Keto Reduction to a Methylene Unit What is the reducing agent for this reaction?

  14. Coenzyme A: an Activated Carrier of Two Carbon Fragments Coenzyme A structure Acetyl CoA + H2O ↔ Acetate + CoA + H+ ∆G°ʹ = -31 kJ/mol Is acetyl coenzyme A adinucleotide?

  15. Activated Carries Utilized in Metabolism

  16. Coenzymes Derived from Vitamins What coenzymes are derived from these vitamins?

  17. Metabolic Regulation • Substrate accessibility (compartmentalization) • Enzyme amount (transcriptional and translation control) • Catalytic activity • (allosteric control, • covalent modifications, • hormone signaling, and • cell energy status) Energy charge = [ATP] + ½[ADP]/([ATP] + [ADP] + [AMP])

  18. Test Your Knowledge… Does this phosphoarginine metabolite rich in the muscles of certain Invertebrates have a high phosphoryl-transfer potential? What function might this metabolite have?

  19. ∆G of ATP Hydrolysis with Varying [Mg2+] How does decreasing [Mg+2] affect ∆G of ATP hydrolysis? Can this trend be justified?

  20. Chapter 15 Problems: 1-8, 10-16 and 18-20 Workbook Problems: page 84 all questions and Page 85-87 questions 1-7 Please note question 2 page 85 has a typo; the two ΔGs should read ΔG and ΔG◦′

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