Oxidative phosphorylation, coenzyme

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

All six carbons of glucose are liberated as CO2, and a total of four molecules of ATP are formed thus far in substrate-level phosphorylations. The 12 reduced coenzymes produced up to this point can eventually produce a maximum of 34 molecules of ATP in the electron transport and oxidative phosphorylation pathways. A stoichiometric relationship for these subsequent processes is 1... 

Whereas ATP made in glycolysis and the TCA cycle is the result of substrate-level phosphorylation, NADH-dependent ATP synthesis is the result of oxidative phosphorylation. Electrons stored in the form of the reduced coenzymes, NADH or [FADHa], are passed through an elaborate and highly orga-... 

The reduced coenzymes are oxidized by the respiratory chain linked to formation of ATP. Thus, the cycle is the major route for the generation of ATP and is located in the matrix of mitochondria adjacent to the enzymes of the respiratory chain and oxidative phosphorylation. 

ATP synthase reaction has been calculated as approximately 51.6 kJ. It follows that the total energy captured in ATP per mole of glucose oxidized is 1961 kJ, or approximately 68% of the energy of combustion. Most of the ATP is formed by oxidative phosphorylation resulting from the reoxidation of reduced coenzymes by the respiratory chain. The remainder is formed by substrate-level phosphorylation (Table 17—1). 

Thus, in one cycle, eight hydrogen atoms (H+ + e ) are transferred to hydrogen-transmitting coenzymes and later oxidized to water in the respiratory chain. This process is linked to oxidative phosphorylation, i.e., the synthesis of ATP from ADP and inorganic phosphate. 

Where two enzymes compete for the same substrate, we expect to see some form of metabolic control and in this case the concentrations of NADH and acetyl-CoA are the key controlling factors (Figure 6.44). When glucose is not available as a fuel, metabolism switches to 3- oxidation of fatty acids, which generates more than sufficient quantities of both NADH and acetyl-CoA to drive the TCA cycle and to maintain oxidative phosphorylation. Pyruvate dehydrogenase activity is suppressed and pyruvate carboxylase is stimulated by ATP, NADH and acetyl-CoA (strictly speaking by low mitochondrial ratios of ADP/ATP, NAD+/NADH and coenzyme A/acetyl-CoA), so... 

Once in the mitochondrial matrix, acyl-CoA (e.g. palmitoyl-CoA), is degraded by 13-oxidation generating acetyl-CoA for the TCA cycle and reduced coenzymes which supply hydrogen atoms and electrons for oxidative phosphorylation. 

Recall from Figure 3.14 in Section 3.3.2, that each turn of the TCA generates three NADH and an FAD so the total amount of reduced coenzyme made available for oxidative phosphorylation is considerable. 

In the presence of adequate O, the rate of oxidative phosphorylation is dependent on the availability of ADR. The concentrations of ADR and ATR are reciprocally related an accumulation of ADR is accompanied by a decrease in ATR and the amount of energy available to the celL Therefore, ADR accumulation signals the need for ATR synthesis. ADR aUosterically activates isocitrate dehydrogenase, thereby increasing the rate of the citric acid cycle and the production of NADH and FADH. The elevated levels of these reduced coenzymes, in turn, increase the rate of electron transport and ATR synthesis. 

In isocitrate, there is a CHOH group that is available for oxidation via the coenzyme NAD+ and the enzyme isocitrate dehydrogenase. NADH will then be reoxidized via oxidative phosphorylation, and lead to ATP synthesis. The oxidation product from isocitrate is oxalosuccinate, a -ketoacid that easily... 

This sequence of reactions, namely oxidation of CH2-CH2 to CH=CH, then hydration to CH2-CHOH, followed by oxidation to CH2-CO, is a sequence we shall meet again in the -oxidation of fatty acids (see Section 15.4.1). The first oxidation utilizes FAD as coenzyme, the second NAD+. In both cases, participation of the oxidative phosphorylation system allows regeneration of the oxidized coenzyme and the subsequent generation of energy in the form of ATP. 

While NADH exclusively supplies oxidative phosphorylation, NADPH+H" —a very similar coenzyme—is the reducing agent for anabolic pathways. NADPH + is mainly formed in the pentose phosphate pathway (PPP, 1 see p. 152). 

The net outcome is that each rotation of the tricarboxylic acid cycle converts one acetyl residue and two molecules of H2O into two molecules of CO2. At the same time, one GTP, three NADH+H"" and one reduced ubiquinone (QH2) are produced. By oxidative phosphorylation (see p. 122), the cell obtains around nine molecules of ATP from these reduced coenzymes (see p. 146). Together with the directly formed GTP, this yields a total of 10 ATP per acetyl group. 

The simple regulatory mechanism which ensures that ATP synthesis is automatically coordinated with ATP consumption is known as respiratory control. It is based on the fact that the different parts of the oxidative phosphorylation process are coupled via shared coenzymes and other factors (left). 

TABLE 16-1 Stoichiometry of Coenzyme Reduction and ATP Formation in the Aerobic Oxidation of Glucose via Glycolysis, the Pyruvate Dehydrogenase Complex Reaction, the Citric Acid Cycle, and Oxidative Phosphorylation... 

Oxidative phosphorylation produces most of the ATP made in aerobic cells. Complete oxidation of a molecule of glucose to C02 yields 30 or 32 ATP (Table 19-5). By comparison, glycolysis under anaerobic conditions (lactate fermentation) yields only 2 ATP per glucose. Clearly, the evolution of oxidative phosphorylation provided a tremendous increase in the energy efficiency of catabolism. Complete oxidation to C02 of the coenzyme A derivative of palmitate (16 0), which also occurs in the mitochondrial matrix, yields 108 ATP per palmitoyl-... 

Correct answer = D. Thirteen of the approximately 100 polypeptides required for oxidative phosphorylation are coded for by mitochondrial DNA, including the electron transport components cytochrome c and coenzyme Q. Oxygen directly oxidizes cytochrome oxidase. Succinate dehydrogenase directly reduces FAD. Cyanide inhibits electron flow, proton pumping, and ATP synthesis. 

Glyceraldehyde 3-phosphate dehydrogenase, a tetrameric enzyme of Mr 150 000 containing four identical chains, catalyzes the reversible oxidative phosphorylation of glyceraldehyde 3-phosphate to 1,3-diphosphoglycerate, using NAD+ as a coenzyme (equation 16.11). 

Under aerobic conditions, the glycolytic pathway becomes the initial phase of glucose catabolism (fig. 13.2). The other three components of respiratory metabolism are the tricarboxylic acid (TCA) cycle, which is responsible for further oxidation of pyruvate, the electron-transport chain, which is required for the reoxidation of coenzyme molecules at the expense of molecular oxygen, and the oxidative phosphorylation of ADP to ATP, which is driven by a proton gradient generated in the process of electron transport. Overall, this leads to the potential formation of approximately 30 molecules of ATP per molecule of glucose in the typical eukaryotic cell. 

In this chapter, discussion focuses on the TCA cycle and its central role in the aerobic catabolism of carbohydrates. Chapter 14 explains how the free energy present in the reduced coenzymes that are generated by glycolysis and the TCA cycle is conserved as ATP during the companion process of electron transport and oxidative phosphorylation. 

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