Model of oxidative phosphorylation

1 Electron transport chain reactions The transport reaction of Complex I is 

In the Complex-Ill reaction, the reduced QH2 is re-oxidized to CoQ and cytochrome C is reduced  

In the Complex-IV reaction, the reduced cytochrome C is re-oxidized and oxygen is reduced to form water  

In this reaction a total of four charges are transported across the inner membrane. The apparent equilibrium constant for the reaction is computed 

In the ATP synthesis reaction, catalyzed by the transporter complex FoFi-ATPase, nA H+ ions are transported from the intermembrane space to the matrix  

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Question How could the Mitchell model of oxidative phosphorylation give an H+/e value of 1 in a situation when no protons traversed the membrane ... 

Describe the chemiosmotic model of oxidative phosphorylation and relate experimental evidence that only the proton-motive force links the respiratory chain and ATP synthesis. 

Which of the following experimental observations provide evidence supporting the chemiosmotic model of oxidative phosphorylation ... 

I realize that I will have to skip the chapter on the mitochondria and oxidative phosphorylation which has been developed to such a high degree by Packer and others. This chapter is well known to everybody. Its further interpretation may have been facilitated by the finding that the bacterial membrane (inner membrane) functions in many ways like the mitochondrial membrane and that it can perform active transport. Mitchell s electrochemical model of oxidative phosphorylation has been greatly strengthened by studies on active transport of nutrients in bacterial strains, some of which have defective membrane ATPases. Heppel and his coworkers have provided us with some important guidelines based on experiments carried out by themselves as well as by other laboratories. 

A typical Hansch analysis has been applied to the 50% inhibitory concentrations (ICjo) of oxidative phosphorylation of 11 doubly substituted salicylanilides (Table 37.1) as reported by Williamson and Metcalf [17]. Multiple linear regression leads to the following model ... 

As an illustration of PLS regression (PLSl) we reconsider the inhibitory potencies of oxidative phosphorylation of 11 doubly substituted salicylanilides [ 17] in Table 37.1. An extended Hansch model is defined by the linear free energy relation ... 

The chemi-osmotic theory of oxidative phosphorylation has been reviewed,74 a model for mitochondrial oxidative phosphorylation in which a membrane potential or proton gradient might transmit energy from an oxidation step to ATP synthesis has been proposed,76 and adenine nucleotide transport in mitochondria has been reviewed.76... 

Before the general acceptance of the chemiosmotic model for oxidative phosphorylation, the assumption was that the overall reaction equation would take the following form ... 

The problem of oxidative phosphorylation has been approached through model studies that utilize the phosphorylating potential of metaphosphate. In the mitrochondrial process inorganic phosphate and adenosine diphosphate are converted to adenosine triphosphate. Wieland, in a series of papers (e.g. ref. 31), has shown that a variety of thiolactones can activate inorganic phosphate in the presence of bromine for transfer to adenosine diphosphate (ADP). The intermediate may be an acyl phosphate or a sulfonium salt similar to that postulated by Higuchi and Gensch32 and by Lambeth and Lardy33, viz. 

Optimal flow ratios are also a characteristic of oxidative phosphorylation, and may provide additional information on the relationships between the respiratory response and energy demand stimulation by ADP. Most metabolic processes in living cells are dynamic systems, and the behavior of flows may better reflect complex system mechanisms than do the models dependent on end-point measurements. For example, the ratio of ADP/O describes the state of the end-point capacity of oxidative phosphorylation based on the input flow of ADP. 

The inconsistency between experiment and prediction must lead to the rejection of the model used to describe the system. In the case of oxidative phosphorylation this has led to a refined model, in which the chemiosmotic coupling is visualized as taking place within units of one (or a few) respiratory chain(s) plus ATP synthase, while the pumped protons have only limited access to the bulk phase inside and/or outside the mitochondrion [42]. This more refined model can again be tested by deriving from it flux-force relations according to the MNET approach. A discussion of the refined model can be found in Ref. 43. 

The cardioprotective effect of melatonin is demonstrated in several studies in in vivo and ex vivo experimental rat models or cardiomyocytes, as reviewed by Reiter.30 Melatonin administration in perfused rat hearts subjected to ischemia and reperfusion increased postischemic recovery of function, reduced the duration of ventricular tachycardia and ventricular fibrillation and this was associated with decreased lipid peroxidation products and OH radical formation, indicating an antioxidant effect of melatonin.31 Furthermore, in pinealectomized rats, occlusion of the left coronary artery followed by reperfusion resulted in significant increase in infarct size than in intact animals.32 Melatonin acts as scavenger of oxygen or nitrogen based reactants, stimulates antioxidant enzymes, stabilizes cellular membrane, increases the efficiency of oxidative phosphorylation, reduces leukocyte recruitment and adhesion molecule expression and reduces homocysteine induced damage (reviewed by Duncker33). 

Arsenite is known to have some effect on oxidative phosphorylation. However, as can be seen [Figure 5c] the use of an uncoupler of oxidative phosphorylation (2,l(-dinitrophenol) did not affect accumulation of ethyl acetate. From this it would appear that the main inhibitory effect of arsenite on ethyl acetate accumulation by C. utllls is at the level of acetyl-CoA formation. Thus acetyl-CoA is implicated as a key precursor for synthesis of ethyl acetate supporting a model presented earlier [Figure it]. 

The mosaic nonequilibrium thermodynamics formulation of oxidative phosphorylation uses the chemiosmotic model as a basis, besides assuming that the membrane has certain permeability to protons, and that the ATP synthase is a reversible pump coupled to the hydrolysis of ATP. It is assumed that the reversibility of the reactions allows the coupled transfer of electrons in the respiratory chain for the synthesis of ATP, and the proton gradient across the inner mitochondrial... 

A model for oxidative phosphorylation that illustrates the kind of rules and reaction sequence that could give such a coupled process is shown in (7) [9]. This... 

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