Proton ionophore

Other auxin-like herbicides (2,48) include the chlorobenzoic acids, eg, dicamba and chloramben, and miscellaneous compounds such as picloram, a substituted picolinic acid, and naptalam (see Table 1). Naptalam is not halogenated and is reported to function as an antiauxin, competitively blocking lAA action (199). TIBA is an antiauxin used in receptor site and other plant growth studies at the molecular level (201). Diclofop-methyl and diclofop are also potent, rapid inhibitors of auxin-stimulated response in monocots (93,94). Diclofop is reported to act as a proton ionophore, dissipating cell membrane potential and perturbing membrane functions. 

In addition to direct inhibition of the vesicular transport protein, storage of neurotransmitters can be reduced by dissipation of the proton electrochemical gradient. Bafilomycin (a specific inhibitor of the vacuolar H+-ATPase), as well as the proton ionophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and carbonylcyanide p-(trifluoromethoxy) phenylhy-drazone (FCCP) are used experimentally to reduce the vesicular storage of neurotransmitters. Weak bases including amphetamines and ammonium chloride are used to selectively reduce ApH. 

An ionophore is a compound that is capable of selectively carrying ions across a membrane. The ion fits into a specific binding site in a molecule that is hydrophobic enough to cross the membrane. There are calcium-specific ionophores, proton ionophores, sodium ionophores, etc. 

Na+,H+ antiporters (NHE) occur in synaptosomes, glia and neuroblastoma cells [60] (Fig. 5-8B). They are relatively inactive at neutral pH but with a decrease in intracellular pH they produce an efflux of protons at the expense of the Na+ gradient. The NHE transport stoichiometry is 1 1. Activation by an internal pH decrement apparently results from protonation of a cytoplasmic site, which allosterically increases the affinity of the proton ionophoric site. In some cells, the NHE is under additional control by receptor mechanisms. Several growth factors and hormones produce transient cytoplasmic alkalinization, probably by mediating a protein kinase... 

Benz, R. and McLaughlin, S. (1983). The molecular mechanism of action of the proton ionophore FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), Biophys. J., 41, 381-398. 

ADP phosphorylation is tightly coupled to electron transport. Shutting down one shuts down the other. It is well known that if ADP phosphorylation is inhibited by such compounds as oligomycin, electron transport also ceases. If the proton gradient is broken by a proton ionophore, however, such as 2,4-dinitrophenol, electron transport resumes at a rapid pace and no phosphorylation takes place. Such proton ionophores are also termed "uncouplers" of electron transport and ADP phosphorylation. Under normal conditions, the factors limiting ATP production are the pH gradient across the inner mitochondrial membrane and the cellular ADP/ATP ratio. An increase in the proton gradient shuts down phosphorylation and electron transport, whereas an increase in the ADP/ATP ratio stimulates both. Stimulation of oxidative phosphorylation by increases in cellular ADP concentration is termed respiratory control. 

A number of substances inhibit oxidative phosphorylation at specific locations. These may be divided into agents that affect electron transport, those that affect complex V, and those that collapse proton gradients (proton ionophores). Such substances have been used as research tools to unravel the complexities of these pathways, as poisons, and as antibiotics. Inhibition of electron transport inhibits phosphorylation, the extent of which depends on the location of the inhibition site. Thus, if complex I is inactivated, electron transport can still take place using FADH2 as an electron donor. The donor P/O ratio is then 2. 

A proton ionophore "short-circuits" the proton current, so that both the proton gradient and membrane potential across the inner mitochondrial membrane are collapsed. No phosphorylation of ADP can take place, but electron... 

Proton ionophores 2,4-Dinitrophenol Collapses proton gradients Used to control obesity in 1920s... 

Seki A, Kubo I, Sasabe H and Tomioka H 1994 A new anion-sensitive biosensor using an ion-sensitive field effect transistor and a light-driven chloride pump, halorhodopsin Appl. Biochem. Biotechnol. 48 205-11 Fuller B E, Okajima T L and Hong F T 1995 Analysis of the d.c. photoelectric signal from model bacteriorhodopsin membranes d.c. photoconductivity determination by means of the null current method and the effect of proton ionophores Bioelectrochem. Bioenerget. 37 109-24 Cone R A 1967 Early receptor potential photoreversible charge displacement in rhodopsin Science 155 1128-31... 

Chemical uncouplers, also known as proton ionophores, are lipid-soluble compounds that rapidly transport protons from the cytosolic to the matrix side of the inner mitochondrial membrane (Fig. 21.11). Because the proton concentration is higher in the intermembrane space than in the matrix, uncouplers pick up protons from the intermembrane space. Their lipid solubility enables them to diffuse through the inner mitochondrial membrane while carrying protons and release these... 

Figure 12. Variation of the concentration of the free ionophore [L], the protonated ionophore [LH" ], and the potassium-ionophore complex [LK" ] with pH. (Reprinted from Ref. 112 with permission. Copyright Elsevier Science Publishers, Amsterdam.)...

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