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
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
Ilya Prigogine (1977)won Nobel Prize
How are oxidation and reduction involved inmetabolism? 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 alcohol aldehyde Carboxylic acid CO2process alkane
The half reaction of oxidation ofethanol 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
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
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.
“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)
Table 15-1, p.425
Fig. 15-8, p.425
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
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
Fig. 15-11, p.429
Fig. 15-12, p.430
In carbohydrate metabolism, glucose-6-phosphate reactsNADP+ to give 6-phosphoglucono-δ-lactone. In this reaction, whichsubstance is oxidized and which is reduced? Which substance isoxidizing agent and which is reducing agent?
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?
Electron transport andoxidative 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).
Fig. 20-1, p.541
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
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
NADH + H+ + CoQ → NAD+ + CoQH2 Fig. 20-5, p.546
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.
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
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.
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
Cytochromes and other Iron-Containing Proteins of Electron Transport Fig. 20-9, p.551NADH, FMN and CoQ, the cytochromes are macromolecules and found in all typesof organisms and located in membrane.
Fig. 20-13, p.555
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.
Glycerol-phosphate shuttle- This mechanism observed inmammalian muscles and brain. Fig. 20-21, p.561
Malate-aspartate shuttle - Has been found inFig. 20-22, p.562 mammalian kidney, liver and heart.
Table 20-3, p.563
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.