Oxidative phosphorylation enhanced

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... 

The effect of nonfatal injuries such as a 2-hour period of bilateral hind-limb ischemia or a full-thickness scald of 20% of skin surface on the LDso of DNOC and its hyperthermic effect were evaluated in male rats (Stoner 1969). The intraperitoneal LDs° of DNOC was significantly (p<0.001) reduced from 24.8 to 26.2 mg/kg to 14 mg/kg DNOC when DNOC was given 1.5- 24 hours after either type of nonfatal injury. The authors concluded that the toxicity of DNOC was increased by previous trauma. These investigators proposed that this interaction was associated with sequential blocking of the tricarboxylic acid cycle with inhibition of citrate synthetase reaction during the early part of the response to the injury. Because DNOC acts as an uncoupler of oxidative phosphorylation, less ATP is produced. Therefore, the effects of trauma will be enhanced by an uncoupling agent such as DNOC. 

Phenoxy herbicides (2,4-D, mecoprop, dichlorprop) are used to control broad-leaved weeds. Ingestion causes nausea, vomiting, p5rrexia (due to uncoupling of oxidative phosphorylation), hyperventilation, hypoxia and coma. Their elimination is enhanced by urine alkalinisation. Organochlorine pesticides, e.g. dicophane (DDT), may cause convulsions in acute overdose. Treat as for status epilepticus. 

Chalker, B.E. and Taylor, D.L., 1975. Light enhanced calcification, and the role of oxidative phosphorylation in calcification of the coral Acropora cervicornis. Proc. R. Soc. London, Ser. B., 190 323—331. 

Salicylates directly stimulate the central respiratory center and thereby cause hyperventilation and respiratory alkalosis. Moreover, salicylates cause uncoupling of oxidative phosphorylation. As a result, heat production (hyperthermia), oxygen consumption, and metabolic rate may be increased. In addition, salicylates enhance anaerobic glycolysis but inhibit Krebs cycle and transaminase enzymes, all of which lead to accumulation of organic acids and thus to metabolic acidosis. ... 

The belief that alcoholics are more susceptible to the toxicity of 2,4-DNP during occupational exposure (Perkins 1919) may indicate an interaction with ethanol (and possibly other alcohols) or it may simply be a function of the compromised physiological state of alcoholics. 2,4-DNP appears to markedly increase the rate of ethanol metabolism in rat liver slices by 100-160% (Videla and Israel 1970) and in rats in vivo by 20-30% (Israel et al. 1970). Because 2,4-DNP uncouples mitochondrial electron transport from oxidative phosphorylation, the oxidation of NADH to NAD is accelerated in the mitochondria. Reoxidation of NADH rather than the activity of alcohol dehydrogenase is the rate-limiting step in the metabolism of ethanol, and, therefore, the metabolic effect of 2,4-DNP enhances the clearance of ethanol (Eriksson et al. 1974). Because 2,4-DNP is known to augment the rate of respiration and perspiration, 2.7-8.2% of the initial dose of ethanol was also eliminated by expiration and cutaneous evaporation in the rat (Israel et al. 1970). 

Morphological changes do occur in the inner membranes of the mitochondria when active respiration is stimulated by ADP. Fluorescent probes, such as 1-aminonaphthalene-8-sulfonate (ANS) and the antibiotic aurovertin, bind either to the inner membrane (ANS) or directly to ATP synthase (aurovertin). The binding enhances or diminishes fluorescence in response to changes in conformation or hydrophobicity of the inner membrane. Results support the hypothesis that ATP synthase undergoes conformational changes during respiration and oxidative phosphorylation (discussed later). 

In most cells, at least 90% of the molecular oxygen consumed is used in oxidative phosphorylation. The remaining 02 is used in a wide variety of specialized metabolic reactions. At least 200 known enzymes use 02 as a substrate. Because 02 is rather unreactive, virtually all of these 200 enzymes use a metal ion to enhance the reactivity of oxygen, just as cytochrome oxidase does. 

Reperfusion with O2 allows recovery of oxidative phosphorylation, provided that the mitochondrial membrane has maintained some integrity and the mitochondrial transition pore can close. However, it also increases generation of free radicals. The transfer of electrons from CoQ to O2 to generate superoxide is increased. Endothelial production of superoxide by xanthine oxidase also may increase. These radicals may go on to form the hydroxyl radical, which can enhance the damage to components of the electron transport chain and mitochondrial lipids, as well as activate the... 

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