Oxidative phosphorylation heat from

Norepinephrine also increases the permeability of BAT and skeletal mnscle to sodinm. Becanse an increase of intracellnlar Na is potentially toxic to cells, Na, K -ATPase is stimnlated to transport Na+ ont of the cell in exchange for K. The increased hydrolysis of ATP by Na, K -ATPase stimulates the oxidation of fnels and the regeneration of more ATP and heat from oxidative phosphorylation. Over a longer time conrse, thyroid hormone also increases the level of Na, K -ATPase and many of the enzymes of fuel oxidation. Because even at normal room temperatnre ATP ntihzation by Na, K -ATPase acconnts for 20% or more of our basal metabohc rate (BMR), changes in its activity can cause relatively large increases in heat prodnction. 

DNP is a lipophilic molecule that binds reversibly with protons. It dissipates that proton gradient in mitochondria by transferring protons across the inner membrane. The uncoupling of electron transport from oxidative phosphorylation causes the energy from food to be dissipated as heat. DNP causes liver failure because of insufficient ATP synthesis in a metabolically demanding organ. 

The organism utilizes this energy in part as heat—to maintain its body temperature—and partly as chemical energy in the form of ATP gained from oxidative phosphorylation. The net result is ... 

Toxicology. 2,4-Dinitrophenol (2,4-DNP) uncouples oxidative phosphorylation from electron transport, resulting in diminished production of ATP, with the energy dissipated as heat, which can lead to fatal hyperthermia. ... 

Many inhibitors of catabolic pathways cause a decrease in cellular heat dissipation. They are therefore valuable tools to indicate the sources of the dissipation and give clues to the relative importance of each pathway in overall metabolic activity (see reviews by Kemp, 1987, 1993 Monti, 1987, 1991). To give a few examples from these reviews, sodium fluoride is a classical inhibitor of glycolysis and it has been shown to substantially reduce heat dissipation by human erythrocytes, lymphocytes, neutrophils, and murine macrophages, indicating the contribution of this pathway to metabolic activity. Cyanide inhibits oxidative phosphorylation by mitochondria at the cytochrome c oxidase complex (site 3) and studies revealed that it decreased heat production in a mouse LS-L929 fibroblast cell line but had no effect on human erythrocytes and neutrophils and murine macrophages, all of which lack mitochondria. Sodium azide inhibits at the same site and so it should come as no surprise that it had no effect on human neutrophils and lymphocytes, but it did reduce heat production by lymphocyte hybridoma cells, which contain... 

DNOC is an uncoupler of oxidative phosphorylation. In DNOC exposed humans or animals, a portion of the energy formed from the Krebs cycle is therefore not stored as ATP, but is given off as heat. This usually results in signs and symptoms, such as hyperthermia, perspiration, and fatigue, in humans exposed to DNOC. High doses of DNOC, elevated environmental temperatures, or physical exercise tends to exaggerate these effects and can result in death. 

Respiratory Therapeutic doses have been shown to uncouple oxidative phosphorylation in cartilaginous and hepatic mitochondria high doses may actually cause fever due to the heat released from uncoupled respiration. 

DNP is an uncoupler of oxidative phosphorylation. In humans or animals exposed to 2,4-DNP, the energy produced from the Krebs cycle is not stored in adenosine triphosphate (ATP), but is released as heat. This short-circuiting of metabolism results in the characteristic clinical signs of increased basal metabolic rate, oxygen consumption, perspiration, and body temperature. Elevated environmental temperatures may compromise the body s ability to dissipate the heat. 

C. Malignant hyperthermia does not involve central brain control of temperature but is caused by metabolic alterations. Regardless of the source of energy—whether fatty acids or the utilization of ATP to support muscle contraction—the electron transport chain is involved. Uncoupling of oxidation from ADP phosphorylation is caused by uncoupling proteins that dissipate energy as heat. This causes the elevation of body temperature seen in this patient. 

In brown fat, the inner mitochondrial membrane contains thermogenln, a proton transporter that converts the proton-motive force into heat. Certain chemicals (e.g., DNP) have the same effect, uncoupling oxidative phosphorylation from electron transport. 

A. Pentachlorophenol and dinitrophenols uncouple oxidative phosphorylation in the mitochondria. Substrates are metabolized but the energy produced is dissipated as heat instead of producing adenosine triphosphate (ATP). The basal metabolic rate increases, placing increased demands on the cardiorespiratory system. Excess lactic add results from anaerobic glycolysis. 

Some bond dissociation energies corresponding to the dissociation of phosphoryl, thiophosphoryl, and N-alkyl (phosphinimine) compounds are shown in Table 2. In this last case dissociation gives rise to the trivalent PX3 compound and the radical NR. Some of these values have been calculated from the difference between the heats of formation of APX3 and PX3 compounds, whilst others are derived from direct measurements of heats of oxidation. 

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