Energy metabolism uncoupling

Hypothermia—Indirect cryodestruction Metabolic uncoupling Energy deprivation Ionic imbalance Disruption of acid-base balance Waste accumulation Membrane phase transitions Cytoskeletal disassembly Frozen State—Direct cryodestruction Water solidification Hyperosmolality Cell-volume disruption Protein denaturation Tissue shearing Intracellular-ice propagation Membrane disruption Microvascular Thawed State Direct effects... 

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... 

Skeletal muscle uncoupling by ectopic expression of mitochondrial UCP-1 has been shown to result in a lean phenotype in mice characterized by increased EE, resistance to diet-induced obesity, and improved glucose tolerance. UCP-2 is a member of the mitochondrial transporter superfamily that uncouple proton entry in the mitochondrial matrix from ATP synthesis. Although its physiological role remains to be established, UCP-2 is considered a candidate gene for association with energy metabolism and obesity. It is worth noting that the possible association of... 

In addition, exercise also upregulates the expression of the mitochondrial uncoupling protein 2, an energy-balancing factor concerned with ATP formation and free radical management (Vaynman et al., 2006), supporting the view that in brain tissue physical exercise promotes a fundamental mechanism by which key elements of energy metabolism may modulate the substrates of hippocampal synaptic plasticity. 

Uncouples oxidative phosphorylation in the CNS, leading to loss of energy metabolism and decreasing the activity of the sodium pump, causing cerebral edema Inhibits adenosine receptors and phosphodiesterase, increasing cAMP production enhances catecholamine release and effects... 

The uncoupling proteins (UCPs) are located in the inner mitochondrial membrane and are involved in different processes, such as energy metabolism regulation, body weight control, and glucose level control (Echtay, 2007). 

Gullicksen, P.S., W.P.Flatt, R.G. Dean, D.L. Hartzell and C.A. Baile, 2002. Energy metabolism and expression of uncoupling proteins 1,2, and 3 after 21 days of recovery fi om intracerebroventricular mouse leptin inrats. Physiol Behav 75, 473-482. 

For many years, niclosamide (Niclocide) was widely used to treat infestations of cestodes. Niclosamide is a chlorinated salicylamide that inhibits the production of energy derived from anaerobic metabolism. It may also have adenosine triphosphatase (ATPase) stimulating properties. Inhibition of anaerobic incorporation of inorganic phosphate into ATP is detrimental to the parasite. Niclosamide can uncouple oxidative phosphorylation in mammalian mitochondria, but this action requires dosages that are higher than those commonly used in treating worm infections. 

Metabolic effects Salicylates cause uncoupling of oxidative phosphorylation which leads to conversion of energy into heat and may thus produce hyperpyrexia and increased protein catabolism. Larger dose produces hyperglycemia and glycosuria in normal individual while in diabetic patient it produces hypoglycemia which may be due to an enhanced peripheral utilization of glucose and inhibition of... 

Salicylic acid, the major metabolite of aspirin, uncouples the electron transport chain in the mitochondria. This results in (a) increased use of oxygen and production of carbon dioxide, (b) lack of ATP, and (c) excess energy no longer utilized in ATP production. The result is increased respiration and raised temperature. The alterations in respiration lead to alkalosis followed by acidosis. The lack of ATP and loss of respiratory control will cause increased metabolic activity and hypoglycemia after an initial mobilization of glucose from glycogen. 

In brown fat, which is specialized for the production of metabolic heat, electron transfer is uncoupled from ATP synthesis and the energy of fatty acid oxidation is dissipated as heat. 

Corrrect answer = E. When phosphorylation is partially uncoupled from electron flow, one would expect a decrease in the proton gradient across the inner mitochondrial membrane and, hence, impaired ATP synthesis. In an attempt to compensate for this delect in energy capture, metabolism and electron flow to oxygen is increased. This hypermetabolism will be accompanied by elevated body temperature because the energy in fuels is largely wasted, appearing as heat. The electron transport chain will still be inhibited by cyanide. 

DNP is an oxidative phosphorylation uncoupler. It makes the process only about 40% efficient by uncoupling a high energy phosphate molecule from ATP and therefore turning ATP into ADP. To maintain an adequate supply of ATP, the body must step-up production. For this reason metabolism is significantly increased and an incredible amount of calories are burned. During this accelerated metabolic state, and due to the need for ATP production, most of the calories come from fatty acids (adipose/fat tissue). So little or no muscle is lost (With adequate protein intake). 

---