ATP in oxidative phosphorylation

FIGURE 20.1 Pyruvate produced hi glycolysis is oxidized in the tricarboxylic acid (TCA) cycle. Electrons liberated in this oxidation flow through the electron transport chain and drive the synthesis of ATP in oxidative phosphorylation. In eukaryotic cells, this overall process occurs in mitochondria. 

The electron transport system is the place in the cell where electrons generated by oxidation are transferred. Passage of the electrons through the system generates potential energy that is used to make ATP in oxidative phosphorylation. 

Let us check the energy balance of the /3-oxidation. As we can deduce from the reaction sequence, 1 FADH2and 1 NADH -I- H+are formed per 2C fragment. 1 FADH2 furnishes 2 ATP and 1 NADH -4- H+ 3 ATP in oxidative phosphorylation. Thus, 5 ATP are derived from each 2 C unit. 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

Figure 12-14. The creatine phosphate shuttle of heart and skeletal muscle. The shuttle allows rapid transport of high-energy phosphate from the mitochondrial matrix into the cytosol. CKg, creatine kinase concerned with large requirements for ATP, eg, muscular contraction CIC, creatine kinase for maintaining equilibrium between creatine and creatine phosphate and ATP/ADP CKg, creatine kinase coupling glycolysis to creatine phosphate synthesis CK, , mitochondrial creatine kinase mediating creatine phosphate production from ATP formed in oxidative phosphorylation P, pore protein in outer mitochondrial membrane.

Because there are no mitochondria in RBCs, there is no production of ATP by oxidative phosphorylation. 

A dynamic model has been proposed for the synthesis of ATP during oxidative phosphorylation in which ADP and inorganic phosphate combine directly to give a quinquecovalent intermediate. While such a model may be valuable in drawing attention to the possible participation of quinquecovalent intermediates in ATP synthesis, no mention is made of the role of oxidation in this reaction. 

This can be used in several ways. H+-ATPase plays a key role in oxidative phosphorylation (ATP synthesis) as it transfers protons back into the matrix space with simultaneous synthesis of ATP (with temporary enzyme phosphorylation, cf. page 451). 

Figure 22.17 Summary of mechanisms to maintain the ATP/ADP concentration ratio in hypoxic myocardium. A decrease in the ATP/ADP concentration ratio increases the concentrations of AMP and phosphate, which stimulate conversion of glycogen/ glucose to lactic acid and hence ATP generation from glycolysis. The changes also increase the activity of AMP deaminase, which increases the formation and hence the concentration of adenosine. The latter has two major effects, (i) It relaxes smooth muscle in the arterioles, which results in vasodilation that provides more oxygen for aerobic ATP generation (oxidative phosphorylation). (ii) It results in decreased work by the heart (i.e. decrease in contractile activity), (mechanisms given in the text) which decreases ATP utilisation.

The respiratory chain is one of the pathways involved in oxidative phosphorylation (see p. 122). It catalyzes the steps by which electrons are transported from NADH+H or reduced ubiquinone (QH2) to molecular oxygen. Due to the wide difference between the redox potentials of the donor (NADH+H or QH2) and the acceptor (O2), this reaction is strongly exergonic (see p. 18). Most of the energy released is used to establish a proton gradient across the inner mitochondrial membrane (see p. 126), which is then ultimately used to synthesize ATP with the help of ATP synthase. 

The inner membrane itself plays an important part in oxidative phosphorylation. As it is impermeable to protons, the respiratory chain—which pumps protons from the matrix into the intermembrane space via complexes 1, 111, and IV—establishes a proton gradient across the inner membrane, in which the chemical energy released during NADH oxidation is conserved (see p. 126). ATP synthase then uses the energy stored in the gradient to form ATP from ADP and inorganic phosphate. Several of the transport systems are also dependent on the H"" gradient. 

Certain foreign compounds can cause changes in body temperature, which may become a toxic response if they are extreme. Substances such as 2,4-dinitrophenol and salicylic acid will raise body temperature, as they uncouple mitochondrial oxidative phosphorylation. Thus, the energy normally directed into ATP during oxidative phosphorylation is released as heat. Substances that cause vasodilation may cause a decrease in body temperature. 

We saw in Chapter 14 that the energy yield from the production of two molecules of pyruvate from one molecule of glucose in glycolysis is 2 ATP and 2 NADH. In oxidative phosphorylation (Chapter 19), passage of two electrons from NADH to 02 drives the formation of about 2.5 ATP, and passage of two electrons from FADH2 to 02 yields about 1.5 ATP. This stoichiometry allows us to calculate the overall yield of ATP from the complete... 

In the second stage of fatty acid oxidation, the acetyl-CoA is oxidized to C02 in the citric acid cycle. A large fraction of the theoretical yield of free energy from fatty acid oxidation is recovered as ATP by oxidative phosphorylation, the final stage of the oxidative pathway. 

We have now seen how the 20 common amino acids, after losing their nitrogen atoms, are degraded by dehydrogenation, decarboxylation, and other reactions to yield portions of their carbon backbones in the form of six central metabolites that can enter the citric acid cycle. Those portions degraded to acetyl-CoA are completely oxidized to carbon dioxide and water, with generation of ATP by oxidative phosphorylation. 

Cyanobacteria can synthesize ATP by oxidative phosphorylation or by photophosphorylation, although they have neither mitochondria nor chloroplasts. The enzymatic machinery for both processes is in a highly convoluted plasma membrane (see Fig. 1-6). Two protein components function in both processes (Fig. 19-55). The proton-pumping cytochrome b6f complex carries electrons from plastoquinone to cytochrome c6 in photosynthesis, and also carries electrons from ubiquinone to cytochrome c6 in oxidative phosphorylation—the role played by cytochrome bct in mitochondria. Cytochrome c6, homologous to mitochondrial cytochrome c, carries electrons from Complex III to Complex IV in cyanobacteria it can also carry electrons from the cytochrome b f complex to PSI—a role performed in plants by plastocyanin. We therefore see the functional homology between the cyanobacterial cytochrome b f complex and the mitochondrial cytochrome bc1 complex, and between cyanobacterial cytochrome c6 and plant plastocyanin. 

Anotiier characteristic of die inner mitochondrial membrane is the presence of projections on the inside surface, which faces the mitochondrial matrix. See Fig. 18-14. These spherical 85-kDa particles, discovered by Fernandez Moran in 1962 and attached to die membrane tiirough a "stalk", display ATP-hydrolyzing (ATPase) activity. The latter was a clue that the knobs might participate in the synthesis of ATP during oxidative phosphorylation. In fact, tiiey are now recognized as a complex of proteins called coupling factor 1 (F ) or ATP synthase. 

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