Phenols oxidative phosphorylation

Allelopathic inhibition of mineral uptake results from alteration of cellular membrane functions in plant roots. Evidence that allelochemicals alter mineral absorption comes from studies showing changes in mineral concentration in plants that were grown in association with other plants, with debris from other plants, with leachates from other plants, or with specific allelochemicals. More conclusive experiments have shown that specific allelochemicals (phenolic acids and flavonoids) inhibit mineral absorption by excised plant roots. The physiological mechanism of action of these allelochemicals involves the disruption of normal membrane functions in plant cells. These allelochemicals can depolarize the electrical potential difference across membranes, a primary driving force for active absorption of mineral ions. Allelochemicals can also decrease the ATP content of cells by inhibiting electron transport and oxidative phosphorylation, which are two functions of mitochondrial membranes. In addition, allelochemicals can alter the permeability of membranes to mineral ions. Thus, lipophilic allelochemicals can alter mineral absorption by several mechanisms as the chemicals partition into or move through cellular membranes. Which mechanism predominates may depend upon the particular allelochemical, its concentration, and environmental conditions (especially pH). 

Table II. Uncoupling of Oxidative Phosphorylation by Phenols at pH 7.5 and Physicochemical Constants Used ...

Phenolic compounds naturally occurring in plants have induced many physiological responses that duplicate those reported for ozone and/or peroxyacetylnitrate (PAN). Chlorogenic acid is a competitive inhibitor of lAA-oxidase (35) and plant growth is adversely affected by increased concentrations of auxins (36). Concentrations of chlorogenic acid are increased in tobacco tissue exposed to ozone ( ) Phenols inhibit ATP synthesis (37), oxidative phosphorylation ( ) and SH enzyme activity (27) they increase respiration (38), reduce CO2 fixation (22), modify both membrane permeability (40) and oxidation rate of reduced NADH... 

Bithionol (Actamer) is a phenolic derivative whose mode of action is related to uncoupling of parasite-specific fumarate reductase-mediated oxidative phosphorylation. The drug is administered orally and is absorbed from the intestinal tract. Peak blood levels are achieved in 4 to 8 hours. Excretion is mainly by the kidneys. 

We chose 60 compounds with pl50 values ranging from 7.1 to 4.9 and subjected them to regression analysis using several physicochemical parameters (Table I). The 60 compounds contained variations in six positions of the basic structure. Quantitative structure-activity correlations with as many individual uncouplers in one equation have not yet been published. As far as we know, the Hansch approach has been applied to uncouplers of oxidative phosphorylation only twice first in 1965 by Hansch and co-workers to phenols and recently by Muraoka and Terada to N-phenylanthranilic acids. From Muraoka s data we recalculated the correlation with w and o- and obtained an equation which gave the best fit (last equation, Figure 3). 

The mode of action of this group of compounds is diverse and depends on the parental compound. The fungicidal activity of most phenols depends on their ability to uncouple oxidative phosphorylation and therefore prevent the production of ATP which is required for growth. Other substituted aromatics reduce growth rates by reacting with the amino or sulfhydryl groups of essential metabolic compounds. 

The fungicidal activity of the various phenols depends on their ability to uncouple oxidative phosphorylation and thus prevent the incorporation of inorganic phosphate into ATP without effecting electron transport. The result of this inhibition is cell death due to the lack of energy for cellular metabolism. 

Dinitrophenol produces a prolonged choleresis (S39), but the BSP excretion rate remains the same or is slightly elevated (S40). This compound also causes a marked pyrexia, but choleresis is not due to hyperthermia since no change in bile flow occurs when animals are warmed to 42°C (S40). A wide range of related compounds have been tested (P12) phenols and mononitrophenols had no effect isomeric dinitro-phenols had less effect picric acid and 2,4-dinitrophenetole were as effective. 2,4-Dinitrophenol is known to uncouple oxidative phosphorylation, but it is difficult to correlate a decrease in ATP with an increased bile flow. Moreover, the 3,5 isomer which is a more potent uncoupler (B59) has a smaller choleretic effect. 

Schultz (1987) used the ionization constant values (pKa) for predicting the mechanism of toxicity of phenols. Two mechanisms have been proposed polar narcosis and uncoupling of oxidative phosphorylation, based on which equations have been derived to determine the toxicities of phenols. 

Both sets depend exclusively on an electronic effect controlling the population of the toxic anion, an effect analogous to that of phenols in uncoupling oxidative phosphorylation (14). The weaker coefficient of Set 1 relative to Set 2 is probably a consequence of the weaker correlation (r = 0.588 vs. r = 0.896), rather than a real difference in response. The data were extracted from bar graphs in the publication (13) and may have more error than tabulated values. 

Dlnitit>phenol (CAS 25550-58-7) Potent uncoupler of oxidative phosphorylation. Initial findings include hypertension, fever, dyspnea, and tachypnea. May cause methemoglobinemia and harm liver and kidneys. May stain skin at point of oontact. Limited evidence for adverse effects on fetal development, See also p 298. 

Several subgroups of chemicals that fall into the general class of polar, nonspecific toxicants were found to be more toxic than calculated from the respective QSARs (Table 5.4) because they exerted additional specific effects. These outliers from the polar non-specific QSARs comprise, for example, phenols and anilines with < 6.3, > two NO2 substituents and/or > three halogen substituents (Bradbury et al, 1989 Nendza and Seydel, 1990 OECD 1992a). They may act as uncouplers of the oxidative phosphorylation with diverging physiological syndromes and hence their QSARs must use different structural descriptors because their toxicity is caused by different chemical properties. 

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