Electron transport, inhibitors

4 TOXICANT-INDUCED MITOCHONDRIAL APOPTOSIS/NECROSIS 17.4.1 Electron Transport Inhibitors 

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In mitochondria, the allelochemlcals acted primarily as electron transport inhibitors. Malate oxidation was more sensitive than either succinate or NADH oxidation. No evidence for interaction with a specific membrane complex was obtained. Instead, Inhibition of substrate oxidation seems to result from alterations and perturbations produced in the inner membrane as reflected in interference with the behavior of transport processes. The compounds did not act as uncouplers or directly inhibit ATP synthesis. However, naringenin, some of the flavones, and the cinnamic acids dj inhibit the hydrolysis of ATP catalyzed by mitochondrial Mg -ATPase. 

The triazine herbicides currently used are mostly 4,6-alkylarmno-v-triazine compounds with either a 2-chloro, 2-methylthio, or 2-methoxy substituent (Table 23.1). The /V-alkyl groups may be methyl, ethyl, 1-methylethyl (isopropyl), 1,1-dimethylethyl (tertiary-butyl), 1,2-dimethylpropyl, or 2-methylpropanenitrile. Absorbed by roots or leaves of plants, these herbicides are applied either preemergence or postemergence to control annual broadleaf weeds and annual grasses in a wide variety of crops. The triazine herbicides listed in Table 23.1 have the same mechanism of action in plants, as all are photosynthetic electron transport inhibitors. 

Herbicides that inhibit the photochemical reactions of isolated chloroplasts have been called routinely inhibitors of the Hill reaction. This has been done primarily for convenience and because, for many years, their action was evaluated under nonphosphorylating conditions, frequently with ferricyanide as the electron acceptor. In the past few years, more sophisticated studies have been conducted with herbicides and more is known about their differential actions. Consequently, Moreland and Hilton (2) separated herbicidal inhibitors of the photochemically induced reactions into the following classes (a) electron transport inhibitors, (b) uncouplers, (c) energy transfer inhibitors,... 

Electron Transport Inhibitors. Electron transport is inhibited when one or more of the intermediate electron transport carriers are removed or inactivated. The site of action of most herbicidal electron transport inhibitors is considered to be associated closely with photosystem II. Consequently, reactions coupled to photosystem II are inhibited, such as basal electron... 

Energy Transfer Inhibitors. Energy transfer inhibitors act directly on phosphorylation. Like electron transport inhibitors,... 

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). 

The development of toxic symptoms on plants treated with pure electron transport inhibitors, such as simazine, diuron, and the uracils, can be prevented if the plants are supplied exogenously with a respirable carbohydrate (2). This observation suggests that the glycolytic or the mitochondrial system can provide sufficient energy to prevent the appearance of phyto-... 

Isoproturon (Urea) (CH3)2CH y NHCON(CH3)2 Photosynthetic electron transport inhibitor at the photosystem II receptor site... 

Photosynthetic electron transport inhibitor at the photosystem II receptor site... 

Series III Sites of Action of Electron Transport Inhibitors... 

Simple stilbenes (Phe-CH=CH-Phe) include the Vitis vinifera (grape) (Vitaceae) cytotoxic resveratrol (4,3, 5 -trihydroxystilbene), the mitochondrial electron transport inhibitor oxyresveratrol (3,5,2, 4 -tetrahydroxystilbene) and the protein kinase inhibitor piceatannol (3,4,3, 5 -tetrahydroxystilbene), all these compounds having antifungal activity. The isoprenylated stilbene chlorophorin (4-geranyl-3,5,2, 4 -tetrahydroxystilbene) is an antioxidant free radical scavenger (AO/FRS). 

Figure 1. Electron transport inhibitors cyazofamid and azoxystobin...

Mode of action Chitin synthesis inhibitor Electron transport inhibitor Rapid excitation of nervous system by persistent activation of nicotinic acetylcholine receptors Auxin transport inhibitor... 

The halftime for the PPj-induced changes is around 0.4 s which is one-tenth of the half-time when ATP is used as the energy donor [4]. The extent of the changes obtained with PPj is usually about two to three times that obtained with ATP. The effects of PPj and ATP are additive [2], The reoxidation of h-type cytochrome starts when the concentration of PP falls below 25 juM [4], Uncouplers of photophosphorylation and electron transport inhibitors abolish both the PPj and the ATP-in-duced reactions. In line with the results with PP synthesis and hydrolysis, the PPj-induced reactions are not inhibited by oligomycin. 

The A/Xh+ can be generated by light-induced or dark electron transport, as well as by hydrolysis of ATP, GTP or PPj [7,8], The rates of the ATP- and PP -driven reactions are about 70 and 56% of the light-driven reaction, respectively. The addition of both ATP and PPj stimulates the rate more than either alone, and gives a rate almost as high as light. The PP-driven reaction is inhibited by uncouplers of phosphorylation but not by electron-transport inhibitors or oligomycin. The stoicheiometries of ATP and PP hydrolyzed to NADP reduced are 1 and 10, respectively. 

This reaction can also be driven by light [9,10,88] or ATP [9,10,89]. The rates of the ATP and PPj-driven NAD reduction are about 20-30 and 6-12% of the light-driven reduction, respectively. The addition of both PPj and ATP causes a synergistic stimulation. Oligomycin inhibits the ATP-driven reaction but stimulates the PPj- as well as the light-driven reactions with 60-70 and 20-80%, respectively. The PPj-driven reaction is inhibited by uncouplers but not by electron-transport inhibitors. 

R Malkin (1982) Interaction of photosynthetic electron transport inhibitors and the Rieske iron-sulfur center in chloroplasts and the cytochrome bg-f complex. Biochemistry 21 2945-2950... 

DE Fleischman and RK Clayton (1968) The effect of phosphorylation uncouplers and electron transport inhibitors upon spectral shifts and delayed light emission of photosynthetic bacteria. Photochem Photobiol 8 287-298... 

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