The potential energy of the water at the top of a waterfall is transformed into kinetic energy in spectacular fashion.
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 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.
FIGURE 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).
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.
FIGURE 15.9 The role of ATP as energy currency in processes that release energy and processes that use energy.
FIGURE 15.10 (a) The structure of coenzyme A. (b) Space-filling model of coenzyme A.
FIGURE 15.11 The hydrolysis of acetyl-CoA. The products are stabilized by resonance and by dissociation.
FIGURE 15.12 The role of electron transfer and ATP production in metabolism. NAD+, FAD, and ATP are constantly recycled.
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.
FIGURE 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 m ono n ucleotide, which differs from FAD in not having an adenine nucleotide. CoQ is coenzyme Q (see Figure 20.4). Cyt b , cyt c 1, cyt c , and cyt aa 3 are the hemecontaining proteins cytochrome b , cytochrome c 1, cytochrome c , and cytochrome aa 3, respectively.
FIGURE 20.4 The oxidized and reduced forms of coenzyme Q. Coenzyme Q is also called ubiquinone.
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.
FIGURE 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.
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.
FIGURE 20.13 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.
FIGURE 20.21 The glycerol–phosphate shuttle.
FIGURE 20.22 The malate–aspartate shuttle.
Cancer survivor and champion cyclist Lance Armstrong on his way to a third Tour de France victory.
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
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)
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
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).
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
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.
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.
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.