Uncouplers inhibitory

Inhibitory Uncouplers. Inhibitory uncouplers inhibit the reactions affected by both electron transport inhibitors and uncouplers. Hence, they inhibit basal, methylamine-uncoupled, and coupled electron transport with ferricyanide as electron acceptor and water as the electron donor, much like electron transport inhibitors. Coupled noncyclic photophosphorylation is inhibited and the phosphorylation reaction is slightly more sensitive than the reduction of ferricyanide. Cyclic photophosphorylation is also inhibited. NADP reduction, when photosystem II is circumvented with ascorbate + DPIP, is not inhibited however, the associated phosphorylation is inhibited. Inhibitory uncouplers act at both sites 1 and 2 (Figure 2). 

Herbicides that act as inhibitory uncouplers are dinitro-phenols, N-phenylcarbamates, acylanilides, halogenated benzoni-triles, substituted imidazoles, substituted benzimidazoles, bromofenoxim, substituted 2,6-dinitroanilines, pyridinols, and substituted 1,2,4-thiadiazoles (2). 

One example is provided by the optical isomers of l-(a-methyl-benzy])-3-(3,4-dichlorophenyl)urea (17). This chemical is an inhibitory uncoupler. The S-isomer inhibits electron transport, but the R-isomer is noninhibitory. The inactive isomer does not compete with the active isomer at the photosystem II site. The phosphorylation site shows no optical specificity. The two isomers do not differ significantly in their lipophilicity. 

A large number of commercial herbicides interfere with electron transport and ATP production in isolated chloroplasts and mitochondria (1.). These herbicides can be divided into two groups electron transport inhibitors and inhibitory uncouplers ( 1, 2, The dimethylphenylureas, substituted uracils, s-triazines, and pyridazinones have been classified as electron... 

The electron transport inhibitors do not directly affect photophosphorylation or interfere with mitochondrial electron transport and phosphorylation ( 1), However, the inhibitory uncouplers, in addition to interfering with electron transport in thylakoids, uncouple photophosphorylation and oxidative phosphorylation, and inhibit mitochondrial electron transport. 

Mitochondrial Responses. The herbicides referred to as inhibitory uncouplers were so named because at low molar concentrations they satisfy most, if not all, of the criteria established for uncouplers of oxidative phosphorylation. However, at higher molar concentrations, they also inhibit mitochondrial electron transport ( 1). ... 

The permeability of chloroplast membranes to endogenous K" " was also increased by FCCP and the inhibitory uncouplers, but not... 

The inhibitory uncouplers, but not diuron and 2,3-DCIPC, also altered the permeability to protons of artificial, purely lipoidal, liposome membranes. In the system (Figure 3A), electrons flow... 

Reference will be made to several herbicides which can be classed as multisite inhibitors. Many of these herbicides have clearly established primary target sites. Examples of such herbicides are the hydroxyben-zonitriles and dinitrophenols, which inhibit and uncouple photosynthetic electron transport (see Chapter 1). However, they are clearly mitochondrial electron transport inhibitory uncouplers (Section 5.1), which is accepted as contributing to their overall mode of action, and their inclusion here is justified. 

Although there are several mechanisms by which respiratory electron transport can be inhibited, the compounds in Figure 5.2 are classed as inhibitory uncouplers. " This activity is not restricted to mitochondrial electron transport as photosystem II (PSII) electron transport and phosphorylation are also affected by dinitrophenols and hydroxybenzonitriles (Refs. 3-5 and Chapter 1). In isolated mitochondrial preparations, lower concentrations of herbicides uncouple oxidative phosphorylation, that is, promote electron transport, without ATP synthesis, whereas higher concentrations inhibit electron transport. Fedtke calculated that uncoupling is 2-10 times more sensitive for a range of phenolic/acidic compounds." A similar difference has also been reported for dinoterb (Figure 5.2), which uncouples oxidative phosphorylation at 0.05-0.15 mM and inhibits respiration at 0.5-1.0mM. ... 

Figure 5.2. Examples of herbicides which have a primary action as inhibitory uncouplers.

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