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Oxidative phosphorylation uncoupling agents

Figure 12-8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuit is created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to the outside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone C, cytochrome c F Fq, protein subunits which utilize energy from the proton gradient to promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H" across the membrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conduction of H" through Fq. Figure 12-8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuit is created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to the outside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone C, cytochrome c F Fq, protein subunits which utilize energy from the proton gradient to promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H" across the membrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conduction of H" through Fq.
Answer C. The toxic agent (example, 2,4-dinitrophenol) would uncouple oxidative phosphorylation, leading to a fall in ATP levels, increased respiration, and increased substrate utilization. [Pg.189]

Oxidative Phosphorylation. Oxidative phosphorylation, that is the production of ATP during the passage of electrons down the terminal electron transport chain, may be disrupted in two distinct ways. Compounds that divorce the process of electron transport and the phosphorylation of ADP are termed uncoupling agents. They permit NADH and succinate to be oxidised via the electron transport chain without the production of ATP and are lethal. Oxidative phosphorylation may also be inhibited directly, thus preventing the oxidation of NADH and succinate. Several products are available that exploit these modes of action. Characteristically, they have wide activity spectra that span major disciplines of pesticide use. [Pg.101]

A few caveats are in order as to what defines a lead. Firstly, a lead is more than just a compound that shows a defined level of activity in a primary screen. The screen must have been validated usually this will be by obtaining the expected responses from pharmacological standards or known drugs. Any reasons for false positives must be understood. Certain substances such as chemically reactive or unstable compounds, protein denaturants, membrane destabilizing agents or uncouplers of oxidative phosphorylation will record as active in a great variety of screens. These must be recognized and eliminated by suitable secondary procedures. [Pg.79]

The control of lice, mites and warbleflies continues to be achieved by the older agents. The selection pressure that caused resistance in cattle ticks and sheep blowfly has not been encountered by these other ectoparasites since their less frequent incidence has required less insecticide/acaricide usage. In addition to the OPs, rotenone (92) (the active principle of derris), an uncoupler of oxidative phosphorylation, continues to be used to combat mange. [Pg.218]

Agents that uncouple oxidative phosphorylation in mitochondria uncouple photoelectron transport and ATP formation in photosynthesis. Explain. [Pg.1357]

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. [Pg.89]

Phosphorus is an oxidizing agent that, when exposed to air, may burn spontaneously. Thus, direct contact may result in both thermal and chemical burns. Second- and third-degree burns can be seen at the point of contact. When absorbed, phosphorus will act as a cellular poison by uncoupling oxidative phosphorylation. [Pg.2000]

Certain chemical substances have been known for many years to uncouple oxidation from phosphorylation and to inhibit active transport, and for this reason they are named uncoupling agents. They are believed to act by rendering the membrane permeable to protons, hence short-circuiting the potential gradient or proton-motive force. [Pg.310]

ANTIFUNGAL, ANTIMICROBIAL and ANTIINFLAMMATORY activity, and to be a powerful cytotoxic agent (functioning by DNA intercalation and uncoupling of oxidative phosphorylation). It is an ENZYME INHIBITOR (alanine aminotransferase and human plasma diamine oxidase). It shows antiplaque activity, and has been used in toothpastes and oral rinses. Causes temporary change in intraocular pressure. Sanomigran pizotifen. [Pg.252]

Uncoupling Oxidative Phosphorylation. The importance of an acidic proton for activity has long been recognized. A mechanism proposed for classical uncouplers (11 ) is that such agents act as ionophores (possibly synergistically with natural ionophores) transporting protons into mitochondria and cations out. In such a case it is reasonable that ionic character is important. The quantitation of the contribution of pKa to activity vis-a-vis partition coefficients has been subjective and conflicting in many cases (1, 12). [Pg.503]

As an alternative test of distribution coefficients it is informative to look at a single biological activity, uncoupling oxidative phosphorylation, by a variety of classes of agents. [Pg.508]

Cheng, S., Clancy, C.J., Nguyen, KT, Clapp, W, and Nguyen, M.H. (2007) A Candida albicans petite mutant strain with uncoupled oxidative phosphorylation overexpresses MDRl and has diminished susceptibility to fluconazole and voriconazole. Antimicrobial Agents and Chemotherapy, 51, 1855-1858. [Pg.190]

A group of antibiotics (e.g., valinomycin, nigericin, and gramicidin A) transport cations across the cell membrane. Such agents, known as ionophores, are widely used to probe membrane structure and function. Ionophores uncouple oxidative phosphorylation. Valinomycin, a cyclic peptide (Figure 14-17), forms a lipid-soluble complex with K+ that readily passes through the inner membrane, whereas K+ by itself does not. In the valinomycin-K complex, hydrophobic groups, present on the outside, facilitate transport of the complex in the lipid environment ... [Pg.261]

Agents that uncouple ETS from oxidative phosphorylation dissipate the proton gradient. [Pg.350]

If the inner mitochondrial membrane is damaged such that it no longer provides a barrier to the movement of protons, then the proton electrochemical gradient is destroyed and oxidative phosphorylation will not occur. Uncoupling agents, such as 2,4-dinitrophenol, which permeabilize the inner mitochondrial membrane to protons, also inhibits oxidative phosphorylation for the same reason. [Pg.352]


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See also in sourсe #XX -- [ Pg.261 ]




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Oxidation agent

Oxidation oxidizing agent

Oxidative phosphorylation

Oxidative phosphorylation uncouplers

Oxidative phosphorylation uncoupling

Oxidizing agents

Oxidizing agents oxidants

Phosphorylating agent

Phosphorylation agents

Uncoupled

Uncoupler

Uncoupler, phosphorylation

Uncouplers

Uncoupling

Uncoupling Agents of Oxidative Phosphorylation

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