Oxidative phosphorylation respiratory control

See also Chemiosmotic Coupling, Oxidative Phosphorylation, Uncoupling ETS and Oxidative Phosphorylation, Respiratory Control... 

Integrity of Mitochondrial Membranes Uncoupling ETS and Oxidative Phosphorylation Respiratory Control Oxidases and Oxygenases... 

In most tissues, where the primary role of the citric acid cycle is in energy-yielding metabohsm, respiratory control via the respiratory chain and oxidative phosphorylation regulates citric acid cycle activity (Chapter 14). Thus, activity is immediately dependent on the supply of NAD, which in turn, because of the tight couphng between oxidation and phosphorylation, is dependent on the availabihty of ADP and hence, ulti-... 

The rates of oxidative phosphorylation and the citric acid cycle are closely coordinated, and are dependent mainly on the availability of and ADR If is limited, the rate of oxidative phosphorylation decreases, and the concentrations of NADH and FADH increase. The accumulation of NADH, in turn, inhibits the citric acid cycle. The coordinated regulation of these pathways is known as respiratory control. ... 

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). 

Active fish have a better developed capillary system in the red muscle to supply oxygen to the mitochondria, and a higher haematocrit (Blaxter et al., 1971). The red muscle tissue also contains more cytochromes (respiratory proteins), and exhibits more cytochrome oxidase activity, which is responsible for transferring electrons in die respiratory chain, more efficient respiration control (oxidative phosphorylation and P/O coefficient) and a greater Atkinson charge, which characterizes energy reserve accumulated in adenyl nucleotides ... 

Now that it is established that cestodes possess all the components of a electron transport system, is the latter functional Weinbach von Brand (952) failed to demonstrate either respiratory control or oxidative phosphorylation in T. taeniaeformis, although they regarded this as a technical rather than a physiological problem. However, there is good evidence that isolated mitochondria from M. expansa (124-127) and H. diminuta (663, 978) are capable of oxidative phosphorylation and respiratory control. The demonstration that a preparation of H. diminuta mitochondria will oxidise a range of substrates, exhibiting respiratory control, is shown in Table 5.14. Similarly, mitochondria from Diphyllo-bothrium latum can oxidise NADH (728) and succinate (729). It is likely that the classical mammalian-type part of the cytochrome chain in cestodes is capable of oxidative phosphorylation, but there is no evidence for ATP synthesis occurring on the alternative branch from the quinone or vitamin K/cytochrome b complex to cytochrome o. 

ADP phosphorylation is tightly coupled to electron transport. Shutting down one shuts down the other. It is well known that if ADP phosphorylation is inhibited by such compounds as oligomycin, electron transport also ceases. If the proton gradient is broken by a proton ionophore, however, such as 2,4-dinitrophenol, electron transport resumes at a rapid pace and no phosphorylation takes place. Such proton ionophores are also termed "uncouplers" of electron transport and ADP phosphorylation. Under normal conditions, the factors limiting ATP production are the pH gradient across the inner mitochondrial membrane and the cellular ADP/ATP ratio. An increase in the proton gradient shuts down phosphorylation and electron transport, whereas an increase in the ADP/ATP ratio stimulates both. Stimulation of oxidative phosphorylation by increases in cellular ADP concentration is termed respiratory control. 

The regulation of the rate of oxidative phosphorylation by the ADP level is called respiratory control or acceptor control. The level of ADP likewise affects the rate of the citric acid cycle because of its need for NAD+ and FAD. The physiological significance of this regulatory mechanism is evident. The ADP level increases when ATP is consumed, and so oxidative phosphorylation is coupled to the utilization of ATP. Electrons do not flow from fuel molecules to O ... 

Luft et al50 reported a case of severe hypermetabolism of non-thyroid origin and a defect in the maintenance of mitochondrial respiratory control. DiMauro et al51 isolated mitochondrial fractions from such a patient and studies of oxidative phosphorylation showed defective respiratory control and normal phosphorylation capacity (loose coupling). The rate of energy-dependent calcium uptake by isolated mitochondria was normal, but the amount of calcium accumulated was much decreased. Calcium could not be retained and was spontaneously released into the medium within 30 seconds. "Recycling" of calcium between mitochondria and cytosol may take place in vivo and result in sustained stimulation of respiration and loose coup-... 

Mercury is a reactive element and its toxicity is probably due to interaction with proteins. Mercury has a particular affinity for sulphydryl groups in proteins and consequently is an inhibitor of various enzymes such as membrane ATPase, which are sulphydryl dependent. It can also react with amino, phosphoryl and carboxyl groups. Brain pyruvate metabolism is known to be inhibited by mercury, as are lactate dehydrogenase and fatty acid synthetase. The accumulation of mercury in lysosomes increases the activity of lysomal acid phosphatase which may be a cause of toxicity as lysosomal damage releases various hydrolytic enzymes into the cell, which can then cause cellular damage. Mercury accumulates in the kidney and is believed to cause uncoupling of oxidative phsophorylation in the mitochondria of the kidney cells. Thus, a number of mitochondrial enzymes are inhibited by Hg2+. These effects on the mitochondria will lead to a reduction of respiratory control in the renal cells and their functions such as solute reabsorption, will be compromised. 

The dependence of oxidative phosphorylation on ADP reveals an important general feature of this process Respiration is tightly coupled to the synthesis of ATP. Not only is ATP synthesis absolutely dependent on continued electron flow from substrates to oxygen, but electron flow in normal mitochondria occurs only when ATP is being synthesized as well. This regulatory phenomenon, called respiratory control, makes biological sense, because it ensures that substrates will not be oxidized wastefully. Instead, their utilization is controlled by the physiological need for ATP. 

The regulation of the rate of oxidative phosphorylation by the availability of ADP is referred to as respiratory control. 

McCandless, D.W. and Abel, M. (1980). The effect unconjugated bilirubin on regional cerebellar energy metabolism. Neurobehav. Toxicol. 2 81-84 Menken, M., and Weidenback, E.C. (1967). Oxidative phosphorylation and respiratory control of brain mitochondria isolated from kemicteric rats. J. Neurochem. 14 189-193 Menken, M., Waggoner, J.G., and Berlin, N. (1966). The influence of bilirubin on oxidative phosphorylation and related reactions in brain and liver mitochondria. J. Neurochem. 13 1241-1248 Morphis, L., Constantopoulos, A., Matsaniotis, N., and PapapWlis, A. (1982). BiUmbin induced modulation of cerebral protein phosphorylation of cerebral protein phophorylation in neonatal rabbits in-vivo. Science 218 156-159... 

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