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Membranes uncouplers

See also Electron Transport, P/O Ratio, Chemiosmotic Coupling, Integrity of Mitochondrial Membranes, Uncoupling ETS and Oxidative Phosphorylation, The FIFO Complex, Oxidation as a Metabolic Energy Source (from Chapter 12)... [Pg.342]

See also Integrity of Mitochondrial Membranes, Uncoupling ETS and Oxidative Phosphorylation, Figure 15.15... [Pg.350]

To efficiently cross the membrane, uncouplers must be reasonably lipophilic (generally log P > 2). However, this alone is not suffident. A key part of the action of a protonophoric uncoupler is the ability to cross the membrane in the anionic form, and this requires the negative charge to be extensively delocalized, or shielded from the lipid interior of the membrane in some way. For this reason, many of the most potent uncouplers combine bulky lipophilic groups adjacent to the ionizable proton with extended conjugated systems through which the charge can be spread. A typical example of this is malonoben (10), one of the most potent phenolic uncouplers known (Fig. 13.4.3) [100]. [Pg.511]

Mitochondria Inhibition of ATP production inactivation of ATPase, the ADP/ATP translocator, and the enzymes associated with the inner membrane uncoupling of oxidative phosphorylation... [Pg.2837]

Solution—Diffusion Model. In the solution—diffusion model, it is assumed that (/) the RO membrane has a homogeneous, nonporous surface layer (2) both the solute and solvent dissolve in this layer and then each diffuses across it (J) solute and solvent diffusion is uncoupled and each is the result of the particular material s chemical potential gradient across the membrane and (4) the gradients are the result of concentration and pressure differences across the membrane (26,30). The driving force for water transport is primarily a result of the net transmembrane pressure difference and can be represented by equation 5 ... [Pg.147]

Many inhibitors of substrate oxidations, substrate transport, electron transport, and ATP synthesis are known including many well-known toxins (see Sherratt, 1981 Harold, 1986 Nicholls and Ferguson, 1992). These are not discussed here except to mention specific uncouplers of oxidative phosphorylation. Classic uncouplers such as 2,4-dinitrophenol have protonated and unprotonated forms, both of which are lipid soluble and cross the inner mitochondrial membrane discharging the proton gradient. This prevents ATP synthesis and stimulates respiration. [Pg.135]

Clofibrate causes a necrotizing myopathy, particularly in patients with renal failure, nephrotic syndrome or hypothyroidism. The myopathy is painful and myokymia of unknown origin is sometimes present. The mechanism of damage is not known, but p-chlorophenol is a major metabolite of clofibrate and p-chlorophe-nol is a particularly potent uncoupler of cellular oxidative phosphorylation and disrupts the fluidity of lipid membranes. Muscle damage is repaired rapidly on the cessation of treatment. [Pg.344]

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... [Pg.395]

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). [Pg.59]

Uncouplers of oxidative phosphorylation Compounds that uncouple oxidative phosphorylatiou from electron transport in the inner mitochondrial membrane. Most are weak lipophilic acids that can run down the proton gradient across this membrane. [Pg.334]

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.
Uncouplers (eg, dinitrophenol) are amphipathic (Chapter 14) and increase the petmeabihty of the lipoid inner mitochondrial membrane to protons (Figure 12—8), thus teducing the electtochemical potential and shott-citcuiting the ATP synthase. In this way, oxidation can proceed without phosphotylation. [Pg.97]

Certain chemical substances have been known for many years to uncouple oxidation firm phosphorylation and to inhibit active transport, and for this reason they are named imcoupling agerrts. They are beheved to act by rendering the membrane permeable to protons hence short-circuiting the potential gradient or protonmotive force. [Pg.257]

Escher, B. I. Snozzi, M. Schwarzenbach, R. P, Uptake, speciation, and uncoupling activity of substituted phenols in energy transducing membranes, Environ. Sci. Technol. 30, 3071-3079 (1996). [Pg.272]

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. [Pg.456]

Ho NFH, PS Burton, RA Conradi, CL Barsuhn. (1995). A biophysical model of passive and polarized active transport processes in Caco-2 cells Approaches to uncoupling apical and basolateral membrane events in the intact cell. J Pharm Sci 84 21-27. [Pg.331]


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See also in sourсe #XX -- [ Pg.144 , Pg.145 ]




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