The Importance of Energy Changes and Electron Transfer in Metabolism

1. The potential energy of the water at the top of a waterfall is transformed into kinetic energy in spectacular fashion. The Importance of Energy Changes and Electron Transfer in Metabolism

2. The synthesis of glucose and other sugars in plants, the production of ATP from ADP, and the elaboration of proteins and other biological molecules are all processes in which the Gibbs free energy of the system must increase. They occur only through coupling to other processes in which the Gibbs free energy decreases by an even larger amount. There is a local decrease in entropy at the expense of higher entropy of the universe. p.416

3. Ilya Prigogine (1977) won Nobel Prize Surroundings? System?

4. How are oxidation and reduction involved in metabolism? • Oxidation-reduction reactions: redox reactions; electrons are transferred from donor to acceptor. • Oxidation : loss of electrons; reduction: the gain of electrons • Substance that losses e- : the one that is oxidized (reducing agent/reductant) • Substance that gains e- : the one that is reduced (oxidizing agent/oxidant) eg. Oxidation process alcohol aldehyde Carboxylic acid CO2 alkane

5. The half reaction of oxidation of ethanol to acetaldehyde Many biologically important redox reactions involve coenzymes, such as NADH and FADH2. These coenzymes appear in many reactions as one of the half-reactions that can be written for a redox reaction. p.420

6. Another important electron acceptor is the oxidized form of FADH2. Other several coenzymes contain flavin group; derived from the vitamin riboflavin (vit B2) p.421

7. ATP can be hydrolized easily and the reaction releases energy • The coupling of energy-producing reactions and energy-requiring reactions is a central feature in metabolism of all organisms • The phosphorylation of ADP to produce ATP requires energy (can be supplied by oxidation of nutrients) • The hydrolysis from ATP to ADP releases energy FIGURE 15.5 The phosphoric anhydride bonds in ATP are “highenergy” bonds, referring to the fact that they require or release convenient amounts of energy, depending on the direction of the reaction.

8. “High energy bond” • High energy bond: term for a reaction in which hydrolysis for a specific bond releases a useful amount of energy. • Another way to indicate such a bond is ~P. • The energy of hydrolysis of ATP is not stored energy, just an electric current – ATP and electric current must be produced when they are needed. FIGURE 15.7 Hydrolysis of ATP to ADP (and/or hydrolysis of ADP to AMP)

9. Table 15-1, p.425

10. Fig. 15-8, p.425

11. The oxidation processes takes place when the organism needs the energy that can be generated by the hydrolysis of ATP Example: Let’s examine biological reaction that release energy. Glucose 2 Lactate ions ∆G°’= -184.5 kJmol-1= -44.1 kcal mol-1 2 ADP + 2 Pi 2 ATP ∆G°’= 61.0 kJ m mol-1= 14.6 kcal mol-1 The overall reaction: Glucose + 2 ADP + 2 Pi 2 Lactate ions + 2 ATP The hydrolysis of ATP produced by breakdown of glucose can be coupled by endergonic processes. eg. muscle contraction in exercise (jogger/long distance-swimmer) Fig. 15-9, p.426

12. Activation process is where a step frequently encountered in metabolism. A component of metabolic pathway (metabolite) is bonded to other molecule, coenzyme, and the free enrgy change for breaking this new bond is negative. eg. A – metabolite, B – substance A + coenzyme A-coenzyme A-coenzyme + B AB + coenzyme Example of coenzyme: coenzyme A (CoA) Fig. 15-10, p.428

13. Fig. 15-11, p.429

14. Fig. 15-12, p.430

15. Question review • In carbohydrate metabolism, glucose-6-phosphate reacts NADP+ to give 6-phosphoglucono-δ-lactone. In this reaction, which substance is oxidized and which is reduced? Which substance is oxidizing agent and which is reducing agent?

16. there is a reaction in which succinate reacts with FAD to give fumarate and FADH2. In this reaction, which substance is oxidized and which is reduced? Which substance is oxidizing agent and which is reducing agent?

17. Electron transport and oxidative phosphorylation

18. Oxidative phosphorylation • Oxidative phosphorylation: the synthesis of ATP from ADP using energy from mitochondrial electron transfer from NADH + H+ and FADH2 to O2. (ADP + Pi ATP) • Give rise to most of the ATP production associated with the complete oxidation of glucose. • Substrate-level phosphorylation: the synthesis of ATP from ADP using energy from the direct metabolism of a high energy reactant. (A-P + ADP B + ATP). This reaction occur in glycolysis and Kreb cycle (carbohydrate metabolism).

19. Fig. 20-1, p.541

20. C6H12O6 + 6O2 6CO2 + 6H2O + 36 ATP Note: on average, 2.5 moles of ATP are generated for each mole of NADH and 1.5 moles of ATP are produced for each mole of FADH2. Fig. 20-2, p.541

21. Essential information • The e- transport chain consists of four multi-subunit membrane-bound complexes and two mobile e- carriers (CoQ and cytochrome c) • The reaction that take place in three of these complexes generate enough energy to drive the phosphorylation of ADP to ATP. • Complex I • known as NAD-CoQ oxidoreductase – catalyzes the first steps of e- transport chain. (NADH to CoQ) • this complex includes several proteins that contain an iron-sulfur cluster and the flavoprotein that oxidizes NADH. • proven to be a challenging task because of its complexity (iron-sulfur clusters). • CoQ is mobile - it is free to move in the membrane and pass the e- to complex III for further transport to O2

22. NADH + H+ + CoQ → NAD+ + CoQH2 Fig. 20-5, p.546

23. Complex II • catalyzes the transfer of e- to CoQ, known as succinate-CoQ oxidoreductase. • its source of e- is differs from oxidizable substrate (NADH) – the substrate is succinate (from TCA/Kreb cycle), which is oxidized to fumarate by a flavin enzyme. Succinate + E-FAD → Fumarate + E-FADH2 E-FADH2 + Fe-Soxidized → E-FAD + Fe-Sreduced Fe-Sreduced + CoQ + 2H+ → Fe-Soxidized + CoQH2 • the overall reaction is exergonic, but there’s not enough energy to drive ATP production + no hydrogen ions pumped out of the matrix during this step.

24. Complex III • CoQH2-cytochrome c oxidoreductase (cyt reductase) catalyzes the oxidation of reduced coenzyme Q (CoQH2) – the e- are passed along to cyt c. CoQH2 + 2 Cyt c [Fe (III)] → CoQ + 2 Cyt c [Fe (II)] + 2 H+ note: the oxidation of CoQ involves two e-, whereas the reduction of Fe (III) to Fe (II) requires only one e- → two molecules of cyt c are required for every molecule of CoQ

25. Complex IV • The 4th complex, cytochrome c oxidase, catalyzes the final steps of e- transport → transfer the e- from cyt c to oxygen. • cytochrome c oxidase is an integral part of the inner mitochondrial membrane and contains cyt a and a3 and two Cu2+ (is an intermediate e- acceptors that lie between two a-type cyt). • The overall reaction: 2 Cyt c [Fe(II)] + 2 H+ + ½ O2 → 2 Cyt c [Fe(III)] + H2O Cyt c → Cyt a → Cu2+ → Cyt a3 → O2 • Both cyt a form the complex known as cytochrome oxidase. The reduced cytochrome oxidase is then oxidized by O2, which reduced to water.

26. So, from all four complexes, there are 3 places where e- transport is coupled to ATP production by proton pumping: • NADH dehydrogenase reaction • Oxidation of cyt b • Reaction of cytochrome oxidase with O2

27. Cytochromes and other Iron-Containing Proteins of Electron Transport Fig. 20-9, p.551 NADH, FMN and CoQ, the cytochromes are macromolecules and found in all types of organisms and located in membrane.

28. p.551

29. Fig. 20-13, p.555

30. What are shuttle mechanism? • In glycolysis (carbohydrate metabolism), the NADH produced in cytosol, but NADH in the cytosol cannot cross the inner mitochondrial membrane to enter the e- transport chain. • The e- can be transferred to a carrier that can cross the membrane. • The number of ATP generated depends on the nature of the carrier.

31. Glycerol-phosphate shuttle - This mechanism observed in mammalian muscles and brain. Fig. 20-21, p.561

32. Malate-aspartate shuttle - Has been found in mammalian kidney, liver and heart. Fig. 20-22, p.562

33. Table 20-3, p.563

34. 4 different sources of energy available for working muscles after rest: • Creatine phosphate- reacts directly in substrate-level phosphorylation to produce ATP • Glucose from glycogen muscles stores; initially consumed by anaerobic metabolism • Glucose from the liver (glycogen stores and gluconeogenesis) – consumed by anaerobic metabolism • Aerobic metabolism in the muscles mitochondria. Sports and metabolism Trained athletes are more aware of the results of anaerobic and aerobic metabolism than nonathletes