Aerobic phosphorylation

It was demonstrated that the rate of aerobic phosphorylation in rat liver mitochondria is depressed by dicoumarol [274]. Antibacterial activity of dicoumarol has been suggested to be related to its uncoupling characteristic [10]. This compound was reported to be a powerful uncoupler of oxidative phosphoiylation, which inhibits phosphorylation at every step in the electron transport chain [275]. 

RK Crane, F Lipmann. The effect of arsenate on aerobic phosphorylation. J Biol Chem 201 235-243, 1953. 

One line of attack on the problem of aerobic phosphorylation relates to the efficiency with which the energy released during the oxidative reactions can bring about the formation of high-energy phosphate linkages. It is of course only the maximum attainable values which are of any real theoretical interest. The direct measurement of ATP formed in the enzyme... 

There is reason to believe that the phosphorylation coupled to this anaerobic dismutation reaction is similar in mechanism to that observed in the first stage of the aerobic phosphorylation scheme. Loomis and Lipmann found that the metabolic poison 2,4-dinitrophenol has an uncoupling ... 

Engelhardt had encountered aerobic phosphorylation in mammalian and avian intact erythrocytes in the presence of redox dyes, with glucose as a metabolite. 

Transfer of Phosphate from Phosphocreatine to Glucose—Here phosphocreatine is the donor of phosphate to adenylic acid forming adenosine triphosphate which passes its acid-labile phosphate over to the sugar. The adenylic acid system acts in a catalytic manner as a carrier of phosphate between phosphocreatine and glucose just as it acts catalytically in aerobic phosphorylation as a carrier of inorganic phosphate to the phosphate acceptor. If sufficiently active, adenosinetriphosphatase will interfere with the phosphorylation of the acceptor to a similar extent in both cases. 

Ochoa, S. (1943) EfiSciency of aerobic phosphorylation in cell-free heart extracts. J. Biol. Chem. 151, 498. 

Some months later, Kalckar, on a visit to St. Louis, brought us the ti ngs that Marianne Grunberg-Manago and Ochoa had penetrated RNA synthesis in depth. While studying aerobic phosphorylation in extracts of Azotobacter they were astute enough to observe the conversion of added ADP to an RNA-like polymer. They purified the responsible enzyme and observed its capacity to polymerize ADP and other ribonucleoside diphosphates, and in the reverse direction, to phosphorolyze the polynucleotide product ... 

Glutamic acid is oxidized to completion by the kidney and liver cyclo-phorase suspensions of Green and co-workers (P). The oxidation is associated with aerobic phosphorylation, and requires the presence of adenosine 5 -phosphate (AMP), Mg++, and P. Since aged preparations are stimulated by DPN+ it appears highly probable that cyclophorase preparations contain L-glutamate dehydrogenase and enzymes of the TCA cycle. 

The question may be raised whether the value for a single step is necessarily an integer. As long as the mechanism of aerobic phosphorylation is unknown, this question cannot be answered. 

Earlier workers in this field thought that the first step in phosphorylation was the formation of a phosphorylated substrate molectde. This concept was derived from studies of anaerobic glycolysis (where it holds true), but it has gradually become clear that phosphorylation of the substrates does not occur in aerobic phosphorylation. One reason against this concept is the occurrence of values above one for the phosphorylation quotient. A phosphorylation of the substrate analogous to that occurring in fermentation could not account for values above one. 

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative phosphorylation to produce COg and HgO represents stage 3 of catabolism. The end products of the citric acid cycle, COg and HgO, are the ultimate waste products of aerobic catabolism. As we shall see in Chapter 20, the oxidation of acetyl-CoA during stage 3 metabolism generates most of the energy produced by the cell. 

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. 

Oxidative phosphorylation The greatest quantitative source of in aerobic organisms. Free energy... 

Glucose is metabolized to pyruvate by the pathway of glycolysis, which can occur anaerobically (in the absence of oxygen), when the end product is lactate. Aerobic tissues metabolize pyruvate to acetyl-CoA, which can enter the citric acid cycle for complete oxidation to CO2 and HjO, linked to the formation of ATP in the process of oxidative phosphorylation (Figure 16-2). Glucose is the major fuel of most tissues. 

The citric acid cycle is an integral part of the process by which much of the free energy liberated during the oxidation of fuels is made available. During oxidation of acetyl-CoA, coenzymes are reduced and subsequendy reoxidized in the respiratory chain, hnked to the formation of ATP (oxicktive phosphorylation see Figure 16-2 and also Chapter 12). This process is aerobic, requiring oxygen as the final oxidant of the reduced coenzymes. The enzymes of the citric acid cycle are lo-... 

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.

Under Aerobic Conditions, Muscle Generates ATP Mainly by Oxidative Phosphorylation... 

The major biochemical features of neutrophils are summarized in Table 52-8. Prominent feamres are active aerobic glycolysis, active pentose phosphate pathway, moderately active oxidative phosphorylation (because mitochondria are relatively sparse), and a high content of lysosomal enzymes. Many of the enzymes listed in Table 52-4 are also of importance in the oxidative metabolism of neutrophils (see below). Table 52-9 summarizes the functions of some proteins that are relatively unique to neutrophils. 

Huang, YJ., Walker, D., Chen, W., Klingbeil, M. and Komuniecki, R. (1998b) Expression of pyruvate dehydrogenase isoforms during the aerobic/anaerobic transition in the development of the parasitic nematode, Ascaris suum altered stoichiometry of phosphorylation/inactivation. Archives of Biochemistry and Biophysics 352, 263-270. 

The electron transport chain gets its substrates from the NADH and FADH2 supplied by the TCA cycle. Since the TCA cycle and electron transport are both mitochondrial, the NADH generated by the TCA cycle can feed directly into oxidative phosphorylation. NADH that is generated outside the mitochondria (for example, in aerobic glycolysis) is not transported directly into the mitochondria and oxidized—that would be too easy. 

Mitochondria are the centers for oxidative phosphorylation and the respiratory centers of all cells. While usually aerobic, some mitochondria (e.g. in some bacteria), are known that function anaerobically. These organelles occur ubiquitously in the neuron and its processes (Figs 1-4, 1-6). Their overall shape may change from one type of neuron to another but their basic morphology is identical to that in other cell types. Mitochondria consist morphologically of double-membraned sacs surrounded by protuberances, or cristae, extending from the inner membrane into the matrix space [7]. 

This process of creating ATP, known as electron transport phosphorylation, then, involves two half-cell reactions, one at the electron donation site and the other where the electrons are accepted from the transport chain. Taking aerobic sulfide oxidation as an example, the donating species H2S(aq) gives up electrons, two at a time, to a series of redox complexes. With the loss of each pair of electrons, the sulfide oxidizes first to S°, then thiosulfate, sulfite, and finally sulfate. 

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