Presentation on theme: "The Importance of Energy Changes and Electron Transfer in Metabolism"— Presentation transcript:
1 The Importance of Energy Changes and Electron Transfer in Metabolism The potential energy of the water at the top of a waterfall is transformed into kinetic energy in spectacular fashion.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.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 Surroundings? System? Ilya Prigogine (1977) won Nobel Prize The characteristics of isolated, closed, and open systems. Isolated systems exchange neither matter nor energy with their surroundings. Closed systems may exchange energy, but not matter, with their surroundings. Open systems may exchange either matter or energy with the surroundings.
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 electronsSubstance 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 processFIGURE 15.2 Comparison of the state of reduction of carbon atoms in biomolecules: -CH2O- (fats) >-CHOH- (carbohydrates) >- C=O (carbonyls) >-COOH (carboxyls) > CO2 (carbon dioxide, the final product of catabolism).alcoholaldehydeCarboxylic acidCO2alkane
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 organismsThe phosphorylation of ADP to produce ATP requires energy (can be supplied by oxidation of nutrients)The hydrolysis from ATP to ADP releases energyFIGURE 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 Another way to indicate such a bond is ~P. “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)
10 FIGURE 15.8 When phosphoenolpyruvate is hydrolyzed to pyruvate and phosphate, it results in an increase in entropy. Both the formation of the keto form of pyruvate and the resonance structures of phosphate lead to the increase in entropy.Fig. 15-8, p.425
11 Let’s examine biological reaction that release energy. The oxidation processes takes place when the organism needs the energy that can be generated by the hydrolysis of ATPExample:Let’s examine biological reaction that release energy.Glucose Lactate ions∆G°’= kJmol-1= kcal mol-12 ADP + 2 Pi ATP∆G°’= 61.0 kJ m mol-1= 14.6 kcal mol-1The overall reaction:Glucose + 2 ADP + 2 Pi Lactate ions + 2 ATPFIGURE 15.9 The role of ATP as energy currency in processes that release energy and processes that use energy.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 eg. A – metabolite, B – substance A + coenzyme A-coenzyme 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 – substanceA + coenzyme A-coenzymeA-coenzyme + B AB + coenzymeExample of coenzyme: coenzyme A (CoA)FIGURE (a) The structure of coenzyme A. (b) Space-filling model of coenzyme A.Fig , p.428
13 FIGURE 15. 11 The hydrolysis of acetyl-CoA FIGURE The hydrolysis of acetyl-CoA. The products are stabilized by resonance and by dissociation.Fig , p.429
14 FIGURE The role of electron transfer and ATP production in metabolism. NAD+, FAD, and ATP are constantly recycled.Fig , p.430
15 Question reviewIn 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 FIGURE 20.1 A proton gradient is established across the inner mitochondrial membrane as a result of electron transport. Transfer of electrons through the electron transport chain leads to the pumping of protons from the matrix to the intermembrane space. The proton gradient (also called the pH gradient), together with the membrane potential (a voltage across the membrane), provides the basis of the coupling mechanism that drives ATP synthesis.Fig. 20-1, p.541
20 C6H12O6 + 6O CO2 + 6H2O + 36 ATPFIGURE 20.2 Schematic representation of the electron transport chain, showing sites of proton pumping coupled to oxidative phosphorylation. FMN is the flavin coenzyme f lavin mononucleotide, which differs from FAD in not having an adenine nucleotide. CoQ is coenzyme Q (see Figure 20.4). Cyt b, cyt c1, cyt c, and cyt aa3 are the hemecontaining proteins cytochrome b, cytochrome c1, cytochrome c, and cytochrome aa3, respectively.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 Iknown 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 O2FIGURE 20.4 The oxidized and reduced forms of coenzyme Q. Coenzyme Q is also called ubiquinone.
22 NADH + H+ + CoQ → NAD+ + CoQH2 FIGURE 20.5 The electron transport chain, showing the respiratory complexes. In the reduced cytochromes, the iron is in the Fe(II) oxidation state; in the oxidized cytochromes, the oxygen is in the Fe(III) oxidation state.Fig. 20-5, p.546
23 Complex IIcatalyzes 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-FADH2E-FADH2 + Fe-Soxidized → E-FAD + Fe-SreducedFe-Sreduced + CoQ + 2H+ → Fe-Soxidized + CoQH2the 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 IIICoQH2-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 CoQFIGURE 20.7 The compositions and locations of respiratory complexes in the inner mitochondrial membrane, showing the flow of electrons from NADH to O2. Complex II is not involved and not shown. NADH has accepted electrons from substrates such as pyruvate, isocitrate, -ketoglutarate, and malate. Note that the binding site for NADH is on the matrix side of the membrane. Coenzyme Q is soluble in the lipid bilayer. Complex III contains two b-type cytochromes, which are involved in the Q cycle. Cytochrome c is loosely bound to the membrane, facing the intermembrane space. In Complex IV, the binding site for oxygen lies on the side toward the matrix.
25 Complex IVThe 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)] + H2OCyt c → Cyt a → Cu2+ → Cyt a3 → O2Both 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 reactionOxidation of cyt bReaction of cytochrome oxidase with O2
27 Cytochromes and other Iron-Containing Proteins of Electron Transport FIGURE 20.9 The heme group of cytochromes. (a) Structures of the heme of all b cytochromes and of hemoglobin and myoglobin. The wedge bonds show the fifth and sixth coordination sites of the iron atom. (b) A comparison of the side chains of a and c cytochromes to those of b cytochromes.Fig. 20-9, p.551NADH, FMN and CoQ, the cytochromes are macromolecules and found in all types of organisms and located in membrane.
29 FIGURE The creation of a proton gradient in chemiosmotic coupling. The overall effect of the electron transport reaction series is to move protons (H+) out of the matrix into the intermembrane space, creating a difference in pH across the membrane.Fig , 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 FIGURE The glycerol–phosphate shuttle.Glycerol-phosphate shuttle- This mechanism observed in mammalian muscles and brain.Fig , p.561
32 Malate-aspartate shuttle FIGURE The malate–aspartate shuttle.Malate-aspartate shuttle- Has been found in mammalian kidney, liver and heart.Fig , p.562
34 Aerobic metabolism in the muscles mitochondria. Sports and metabolism 4 different sources of energy available for working muscles after rest:Creatine phosphate- reacts directly in substrate-level phosphorylation to produce ATPGlucose from glycogen muscles stores; initially consumed by anaerobic metabolismGlucose from the liver (glycogen stores and gluconeogenesis) – consumed by anaerobic metabolismAerobic metabolism in the muscles mitochondria.Sports and metabolismTrained athletes are more aware of the results of anaerobic and aerobic metabolism than nonathletesCancer survivor and champion cyclist Lance Armstrong on his way to a third Tour de France victory.