Uncoupling, oxidative phosphorylation

In addition to the above-mentioned properties, the piperidine alkaloids exhibit a wide range of physiological activities. Thus, neuromuscular transmission is shown to be blocked by Ic and Id (72). Mitochondrial respiration is decreased and oxidative phosphorylation uncoupled at low concentrations of Ig (75), which, in addition to cw-6-methyl-2-(cw-6 - -pentadecenyl)piperidine (2c), inhibits the reactions of the Na+, K + -ATPase (14). 

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). 

TABLE 23.3 Examples of Baseline Toxicity (BT), Polar Narcosis (PN), and Oxidative Phosphorylation Uncoupling (OPU) QSARs... 

See also Chemiosmotic Coupling, Oxidative Phosphorylation, Uncoupling ETS and Oxidative Phosphorylation, Respiratory Control... 

Diuron (10 mol/L), as a photosynthetic inhibitor, as well as dinitrophenol (DNP 10 mol/L), as an oxidative phosphorylation uncoupler, facilitated the adverse effect of high temperature. This can testify to the influence of CMS on stabilization of electron transport chain carriers in the lipid membrane. 

That the active concentration of iodide in the thyroid is energy dependent is suggested by several observations. The active concentration of iodide requires oxygen. It is blocked by metabolic poisons, such as cyanide and azides. There is a correlation between concentration ability and rate of oxidative phosphorylation. Uncouplers such as 2,4-dinitrophenol block iodine uptake in the thyroid. 

A. Salicylates - Evidence has been given that aspirin increases bleeding time and decreases blood platelet aggregation, probably by virtue of the acetoxy group. On the other hand, in oxidative phosphorylative uncoupling in mitochondria, the action is due to the salicylic acid moiety. ... 

Azido 4-nitrophenol Oxidative phosphorylation uncoupling site in mitochondria More effective uncoupler than dinitio-phenol, attachment sites on inner mitochondrial membrane subunit 1 of Fi-ATPase (MW 56,000) and a protein of MW 31,000 58-61... 

Also Bradbury and co-workers review the oxidative phosphorylation uncoupling QSARs, which embody these chemicals that are typically weak acids and are represent by phenols, anilines, and pyridines but, different from polar narcotics, include multiple electronegative groups... 

On the contrary, chemical classes not usually identified as acting by a baseline narcosis mode of action, such as the phenols, include chemicals that act through baseline narcosis, polar narcosis, oxidative phosphorylation uncoupling, or electrophilic-based modes of action (Bradbury et al., 2003). 

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