Oxidative phosphorylation control

Sulflutamid or A/-ethylpetfluotoctanesulfonamide [4151 -50-2] CgF yS02NHC2H, is a slow-acting stomach poison used in baits for the control of ants and cockroaches. It acts as an uncoupler of oxidative phosphorylation. 

Moreno-Sachez, R., Devars, S., Lopez-Gomez, F., Uribe, A., Corona, N. (1991). Distribution of control of oxidative phosphorylation in mitochondria oxidizing NAD-linked substrates. Biochim. Biophys. Acta 1060,284-292. 

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-... 

It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in... 

The rate of oxidative phosphorylation is controlled by the supply of ADP and phosphate. 

Where two enzymes compete for the same substrate, we expect to see some form of metabolic control and in this case the concentrations of NADH and acetyl-CoA are the key controlling factors (Figure 6.44). When glucose is not available as a fuel, metabolism switches to 3- oxidation of fatty acids, which generates more than sufficient quantities of both NADH and acetyl-CoA to drive the TCA cycle and to maintain oxidative phosphorylation. Pyruvate dehydrogenase activity is suppressed and pyruvate carboxylase is stimulated by ATP, NADH and acetyl-CoA (strictly speaking by low mitochondrial ratios of ADP/ATP, NAD+/NADH and coenzyme A/acetyl-CoA), so... 

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. ... 

Figure 9.25 Control of the Krebs q/cle and myosin-ATPase by direct effects of Ccf ions and the resultant effects on electron transfer and oxidative phosphorylation in muscle. The stimulation of the Krebs cycle by ions results in an increase in the NADH/NAD concentration ratio, which stimulates electron transfer. The stimulation of myosin-ATPase by Ca lowers the ATP/ADP concentration ratio, which also stimulates electron transfer. The Ca ions are released from the sarcoplasmic reticulum in muscle in response to nervous stimulation. In addition, generation of ADP by myosin ATPase increases the ADP concentration, which stimulates the cycle. Note that a lack of oxygen will prevent generation of ATP (Chapter 13).

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). 

The control of lice, mites and warbleflies continues to be achieved by the older agents. The selection pressure that caused resistance in cattle ticks and sheep blowfly has not been encountered by these other ectoparasites since their less frequent incidence has required less insecticide/acaricide usage. In addition to the OPs, rotenone (92) (the active principle of derris), an uncoupler of oxidative phosphorylation, continues to be used to combat mange. 

Thyroxine and triiodothyronine have many effects, a major one in mammals and birds being stimulation of energy metabolism in tissues. It has long been recognized that a deficiency of thyroid hormone is reflected in an overall lower basal metabolic rate (Chapter 6). Maley and Lardy observed that thyroxine uncouples oxidative phosphorylation (Chapter 18) in isolated mitochondria.117 When mitochondria from animals receiving extra thyroxine were compared with those from control animals, an increased rate of electron transport was observed. However, there was little or no change in the P / O ratio. Thus, the hormone apparently increased the rate of electron transport... 

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 ... 

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