Oxidative phosphorylation regulation

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-... 

EXAMPLE 10.18 How is the extent of uncoupling of oxidative phosphorylation regulated in brown adipose tissue (BAT) ... 

Balaban RS Regulation of oxidative phosphorylation in the mammalian cell. Am J Physiol 1990 258 C377. 

The first is cell injury (cytotoxicity), which can be severe enough to result in cell death. There are many mechanisms by which xenobiotics injure cells. The one considered here is covalent binding to cell macromol-ecules of reactive species of xenobiotics produced by metabolism. These macromolecular targets include DNA, RNA, and protein. If the macromolecule to which the reactive xenobiotic binds is essential for short-term cell survival, eg, a protein or enzyme involved in some critical cellular function such as oxidative phosphorylation or regulation of the permeability of the plasma membrane, then severe effects on cellular function could become evident quite rapidly. 

Fig. 2.2 Simplified scheme of oxidant/antioxidant regulation ofNF-KB activation. Different stimuli, leading to an increase of ROS generation inside the ceU, activate the phosphorylation of IkB inhibitory protein and the subsequent proteolysis. Thioredoxin (Trx) may reduce activated NF-kB proteins facilitating nuclear translocation.Qnce released from IkB, the NF-kB complex translocates into the nucleus and the binding to DNA domain in the promoters and enhancers of genes such as TNF-a, IL-1, proliferation and chemotactic factors, adhesion molecule. Some of these genes, in turn, may further induce NF-kB activation, leading to a vicious circle if the regulatory cellular system escapes from...

Coordinate Regulation of the Citric Acid Cycle and Oxidative Phosphorylation... 

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. ... 

In any cell that depends on aerobic metabolism, if the rate of ATP utilisation increases, the rate of the Krebs cycle, electron transfer and oxidative phosphorylation must also increase. The mechanism of regulation discussed here is for mammalian skeletal muscle since, to provide sufficient ATP to maintain the maximal power output, at least a 50-fold increase in flux through the cycle is required so that the mechanism is easier to study (Figure 9.22). 

Figure 19.18 The role of cyclic GMP and vasodilation in provision and preparation of spermatozoa for fertilisation. Vasodilation is regulated by the concentration of cyclic GMP by relaxation of smooth muscle. The resultant increase in blood flow to the corpora cavernosa results in erection of the penis for the ejaculation of spermatozoa into the vagina. The increase in blood flow to the vaginal smooth muscle provides more oxygen for diffusion into the lumen. Here it provides for oxidative phosphorylation in the mitochondria of the-mid section of the spermatozoa, which provides the ATP for the beating of the flagellum and hence for swimming to the oviduct for fertilisation.

Using the transport systems in the membranes, cells regulate their volume, internal pH value, and ionic environment. They concentrate metabolites that are important for energy metabolism and biosynthesis, and exclude toxic substances. Transport systems also serve to establish ion gradients, which are required for oxidative phosphorylation and stimulation of muscle and nerve cells, for example (see p. 350). 

CoA (see Table 17-1). A similar calculation can be made for the ATP yield from oxidation of each of the amino acids (Chapter 18). Aerobic oxidative pathways that result in electron transfer to 02 accompanied by oxidative phosphorylation therefore account for the vast majority of the ATP produced in catabolism, so the regulation of ATP production by oxidative phosphorylation to match the cell s fluctuating needs for ATP is absolutely essential. 

Oxidative Phosphorylation Is Regulated by Cellular Energy Needs... 

Thyroid hormones are intimately involved in regulating the basal metabolic rate. Liver tissue of animals given excess thyroxine shows an increased rate of 02 consumption and increased heat output (thermogenesis), but the ATP concentration in the tissue is normal. Different explanations have been offered for the thermogenic effect of thyroxine. One is that excess thryroxine causes uncoupling of oxidative phosphorylation in mitochondria. How could such an effect account for the observations Another explanation suggests that the thermogenesis is due to an increased rate of ATP utilization by the thyroxine-stimulated tissue. Is this a reasonable explanation Why ... 

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