1. The potential energy of the water at the top of a waterfall is transformed into kinetic energy in spectacular fashion.The Importance ofEnergy Changes andElectron Transfer inMetabolism
2. The synthesis of glucose and other sugars in plants, the production of ATP from ADP, and the elaboration ofproteins and other biological molecules are all processes in which the Gibbs free energy of the system mustincrease. They occur only through coupling to other processes in which the Gibbs free energy decreases by aneven 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 4. How are oxidation and reduction involved inmetabolism? Oxidation-reduction reactions: redox reactions; electronsare transferred from donor to acceptor. Oxidation : loss of electrons; reduction: the gain ofelectrons Substance that losses e- : the one that is oxidized (reducingagent/reductant) Substance that gains e- : the one that is reduced (oxidizingagent/oxidant)eg. Oxidation alcohol aldehyde Carboxylic acidCO2processalkane 5. The half reaction of oxidation ofethanol to acetaldehydeMany biologicallyimportant redoxreactions involvecoenzymes, such asNADH and FADH2.These coenzymesappear in manyreactions as one ofthe half-reactions thatcan be written for aredox 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 hydrolizedeasily and the reactionreleases energy The coupling of energy-producing reactionsand energy-requiringreactions is a centralfeature in metabolismof all organisms The phosphorylation ofADP to produce ATPrequires energy (can besupplied by oxidationof nutrients) The hydrolysis fromATP to ADP releasesenergyFIGURE 15.5 The phosphoric anhydride bonds in ATP arehighenergy bonds, referring to the fact that they require or releaseconvenient amounts of energy, depending on the direction of thereaction. 8. High energy bond High energy bond: termfor a reaction in whichhydrolysis for a specificbond releases a usefulamount of energy. Another way to indicatesuch a bond is ~P. The energy of hydrolysisof ATP is not storedenergy, just an electriccurrent ATP and electriccurrent must be producedwhen 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 takesplace when the organism needsthe energy that can be generatedby the hydrolysis of ATP Example: Lets 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 Pi2 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 stepfrequently encountered inmetabolism. A component ofmetabolic pathway (metabolite) isbonded to other molecule,coenzyme, and the free enrgychange for breaking this new bond isnegative.eg. A metabolite, B substanceA + coenzyme A-coenzymeA-coenzyme + B AB + coenzymeExample of coenzyme: coenzyme A(CoA) Fig. 15-10, p.428 13. Fig. 15-11, p.429 14. Fig. 15-12, p.430 15. In carbohydrate metabolism, glucose-6-phosphate reactsNADP+ to give 6-phosphoglucono--lactone. In this reaction, whichsubstance is oxidized and which is reduced? Which substance isoxidizing agent and which is reducing agent? 16. there is a reaction in which succinate reacts with FAD to givefumarate and FADH2. In this reaction, which substance is oxidizedand which is reduced? Which substance is oxidizing agent andwhich is reducing agent? 17. Electron transport andoxidative phosphorylation 18. Oxidative phosphorylation: the synthesis of ATP fromADP using energy from mitochondrial electron transferfrom NADH + H+ and FADH2 to O2. (ADP + Pi ATP) Give rise to most of the ATP production associated withthe complete oxidation of glucose. Substrate-level phosphorylation: the synthesis of ATPfrom ADP using energy from the direct metabolism of ahigh 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-subunitmembrane-bound complexes and two mobile e- carriers(CoQ and cytochrome c) The reaction that take place in three of these complexesgenerate enough energy to drive the phosphorylation ofADP to ATP. Complex I known as NAD-CoQ oxidoreductase catalyzes thefirst steps of e- transport chain. (NADH to CoQ) this complex includes several proteins that contain aniron-sulfur cluster and the flavoprotein that oxidizesNADH. proven to be a challenging task because of itscomplexity (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/Krebcycle), 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 + CoQH2 the overall reaction is exergonic, but theres not enoughenergy to drive ATP production + no hydrogen ionspumped 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 forevery 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+ + 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 Proteinsof Electron TransportFig. 20-9, p.551NADH, FMN and CoQ, the cytochromes are macromolecules and found in all typesof organisms and located in membrane. 28. p.551 29. Fig. 20-13, p.555 30. 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 inmammalian muscles and brain. Fig. 20-21, p.561 32. Malate-aspartate shuttle- Has been found inFig. 20-22, p.562 mammalian kidney, liverand heart. 33. Table 20-3, p.563 34. 4 different sources of energyavailable for working musclesafter rest: Creatine phosphate- reactsdirectly in substrate-levelphosphorylation to produceATP Glucose from glycogenmuscles stores; initiallyconsumed by anaerobicmetabolism Glucose from the liver(glycogen stores andgluconeogenesis) consumedby anaerobic metabolism Aerobic metabolism in themuscles mitochondria.