Oxidative phosphorylation of ADP to ATP

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. 

The components of respiratory metabolism include glycolysis, the tricarboxylic acid (TCA) cycle, the electron-transport chain, and the oxidative phosphorylation of ADP to ATP. Glycolysis converts glucose to pyruvate the TCA cycle fully oxidizes the pyruvate (by means of acetyl-CoA) to C02 by transferring electrons stepwise to... 

The coenzyme complex is then broken down in a series of reactions known as P oxidation (11.96). The acetyl coenzyme A produced in the last reaction in Equation 11.96 then enters the Krebs cycle and the long-chain co-enzyme A re-enters the P-oxidation series of reactions, two carbon atoms shorter than when it started. By recycling in this way, the hydrocarbon chain is repeatedly broken down, two atoms at a time, and acetyl coenzyme A units are continually fed into the Krebs cycle where complete oxidation takes place. The coenzyme from stearic acid undergoes the sequence 8 times, yielding nine molecules of acetyl-CoA, each of which leads to regeneration of ATP in the Krebs cycle. The reduced NADH from Equation 11.96 can also effect oxidative phosphorylation of ADP to ATP as described in Equation 11.67. 

Figure 16-2. The citric acid cycle the major catabolic pathway for acetyl-CoA in aerobic organisms. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with HjO, and oxidized to CO2 with the release of reducing equivalents (2H). Subsequent oxidation of 2H in the respiratory chain leads to coupled phosphorylation of ADP to ATP. For one turn of the cycle, 11 are generated via oxidative phosphorylation and one arises at substrate level from the conversion of succinyl-CoA to succinate.

Several enzymes, known collectively as fatty acid oxidase, are found in the mitochondrial matrix or inner membrane adjacent to the respiratory chain. These catalyze the oxidation of acyl-CoA to acetyl-CoA, the system being coupled with the phosphorylation of ADP to ATP (Figure 22-3). 

Phosphorylation of ADP to ATP by mitochondria is driven by an electrochemical proton gradient established across the inner mitochondrial membrane as a consequence of vectoral transport of protons from NADH and succinate during oxidation by the respiratory chain (see Chapter 17). Hence, lipophilic weak acids or bases (such as 2,4-dinitrophenol) that can shuttle protons across membranes will dissipate the proton gradient and uncouple oxidation from ADP phosphorylation. Intrami-tochondrial ADP can be rate-limiting as demonstrated by inhibition of the mitochondrial adenosine nucleotide carrier by atractyloside. Inhibition of ATP synthesis... 

The anaerobic phosphorylation of ADP to ATP in mitochondria offers an excellent site for chemotherapeutic attack. The uncoupling of oxidative phosphorylation would lead to inhibition of ATP synthesis and subsequent starvation of the worms. A number of uncouplers of oxidative phosphorylation are now known, the first being 2,4-dinitrophenol (9) described by Loomis and Lipmann in 1948 [44]. Niclosamide (10) and other salicylanilide anthelmintics have been found to inhibit an-... 

The answer is d. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) Oligomycin inhibits mitochondrial ATPase and thus prevents phosphorylation of ADP to ATP It prevents utilization of energy derived from electron transport for the synthesis of ATP Oligomycin has no effect on coupling but blocks mitochondrial phosphorylation so that both oxidation and phosphorylation cease in its presence. 

The electron transport chain (ETC) or electron transport system (ETS) shown in Figure 16-1 is located on the inner membrane of the mitochondrion and is responsible for the harnessing of free energy released as electrons travel from more reduced (more negative reduction potential, E to more oxidized (more positive carriers to drive the phosphorylation of ADP to ATP. Complex 1 accepts a pair of electrons from NADH ( = -0.32 V)... 

Energy is released as electrons travel from more reduced (more negative reduction potential, E ) to more oxidized (more positive E carriers to drive the phosphorylation of ADP to ATP. 

This reaction illustrates the use of chemical energy originally produced by the oxidation of nutrients and ultimately trapped by phosphorylation of ADP to ATP. Recall from Section 15.10 that ATP does not represent stored energy, just as an electric current does not represent stored energy. The chemical energy of nutrients is released by oxidation and is made available for immediate use on demand by being trapped as ATP. 

In the light reactions of photosynthesis, water is converted to oxygen hy oxidation and NADP+ is reduced to NADPH. The series of redox reactions is coupled to the phosphorylation of ADP to ATP in a process called photophosphorylation. 

Mitochondria produce most of the energy in cells by oxidative phosphorylation. This process combines two distinct but tightly coupled parts Electron transport and phosphorylation of ADP to ATP - as discussed in detail in Chapter 13.1. Most modem insecticides and acaricides that dismpt mitochondrial ATP synthesis [1] interfere with the electron transport (mainly at complex 1, less frequently at complex III) (see Chapter 28.3). 

Oxidative phosphorylation (1) Process in which the energy of electrons is captured in high-energy bonds as phosphate groups combine with ADP to form ATP. (2) The phosphorylation of ADP to ATP that occurs in conjunction with the transit of electrons down the electron transport chain in the inner mitochondrial membrane. 

Thus, by combining the NADH-ubiquinone reductase complex with a heterogeneous fraction solubilized from bovine heart submitochondrial fractions (referred to as hydrophobic protein ) and phospholipids (phosphatidylethanolamine, phosphatidylcholine, cardiolipid), Ragan and Racker and his associates [146] were able to reconstitute vesicles. These vesicles, which can be isolated on sucrose gradients, carry on the phosphorylation of ADP to ATP, and the oxidative phosphorylation is sensitive to uncouplers. 

The stepwise oxidation of NADH and reduction of oxygen to water is obligatorily linked to the phosphorylation of ADP to ATP. Approximately 3 mol of ATP is formed for each mole of NADH that is oxidized. Flavoproteins reduce ubiquinone, which is an intermediate coenzyme in the chain, and approximately 2 mol of ADP is phosphorylated to ATP for each mole of reduced flavoprotein that is oxidized. 

The membrane of the cristae contains the coenzymes associated with electron transport, the oxidation of reduced coenzymes, and the reduction of oxygen to water (section 3.3.1.2). The primary particles on the matrix surface of the cristae contain the enzyme that catalyses the phosphorylation of ADP to ATP (section 3.3.1.3). 

The overall process of oxidation of reduced coenzymes, reduction of oxygen to water, and phosphorylation of ADP to ATP requires intact mitochondria, or intact sealed vesicles of mitochondrial inner membrane prepared by disruption of mitochondria it will not occur with solubilized preparations from mitochondria, or with open fragments of mitochondrial inner membrane. Under normal conditions, these three processes are linked, and none can occur without the others. 

Complex II catalyses the oxidation of reduced flavins and the reduction of ubiquinone. This complex is not associated with phosphorylation of ADP to ATP... 

The processes of oxidation of reduced coenzymes and the phosphorylation of ADP to ATP are normally tightly coupled ... 

Metabolic fuels can only be oxidized when NAD and oxidized flavoproteins are available. Therefore, if there is little or no ADP available in the mitochondria (i.e. it has all been phosphorylated to ATP), there will be an accumulation of reduced coenzymes, and hence a slowing of the rate of oxidation of metabolic fuels. This means that substrates are only oxidized when there is a need for the phosphorylation of ADP to ATP and ADP is available. The availability of ADP is dependent on the utilization of ATP in performing physical and chemical work, as shown in Figure 3.2. 

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