Cell membranes, phenol inhibition

Inhibition of Chloride Passage Across Red Cell Membranes. Phenols inhibit the passage of chloride ion across the red cel 1 membrane. Motais et al. (15) examined this property for some of the same phenols (Table V) as those used for uncoupling studies by Stockdale Selwyn. A fair correlation can be obtained with log D and pKa (eq 19). Half of these phenols are not appreciably ionized under the experimental conditions. Since many nonacidic compounds are also active, we wondered if it really mattered for the unionized phenols whether the pKa was 9 or 10 or 11. Why not use Cp as a parameter which will parallel the pKa for ionized phenols, but will be zero for unionized phenols A superior treatment results when a Cp term is used, eq 20. Cp is the logarithm of the fraction of phenol unionized. The following interpretation is possible Cp is zero for unionized phenols... 

Action on the plasma membrane is the first and most fundamental of the bewildering array of deleterious effects of the cinnamic and benzoic acids. They reduce the transmembrane electrochemical potential with the immediacy and extent of that action depending on the concentration and lipid solubility of the compound.35,37,45,60 Rate of uptake also is concentration and pH-dependent, with transfer into and across the membrane greatest with lower pH conditions and higher external concentrations.60 Phenolic acid-induced depolarization of membranes causes a nonspecific efflux of both anions and cations accompanying the increased cell membrane permeability, and these membrane effects correlate with an inhibition of ion uptake. The phenolic acids suppress absorption of phosphate, potassium, nitrate, and magnesium ions, and overall changes in tissue... 

This effect can be due to sudden variations in salinity (modification in the osmotic pressure on cell membranes), in relatively inhibiting compounds or even in readily biodegradable compounds. Phenols are routinely degraded in coking plants from concentrations of 2.5 g l which are high but kept constant. Meanwhile in refineries, purification must deal with concentrations of some 20 to 100 mg l and could in no way cope with a sudden discharge of phenol-bearing spent caustic for a couple of hours. The same holds true for S above 20 to 30 mg ... 

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). 

Although several allelochemicals (primarily phenolic acids and flavonoids) have been shown to inhibit mineral absorption, only the phenolic acids have been studied at the physiological and biochemical levels to attempt to determine if mineral transport across cellular membranes can be affected directly rather than indirectly. Similar and even more definitive experiments need to be conducted with other allelochemicals that are suspected of inhibiting mineral absorption. Membrane vesicles isolated from plant cells are now being used to elucidate the mechanism of mineral transport across the plasma membrane and tonoplast (67, 68). Such vesicle systems actively transport mineral ions and thus can serve as simplified systems to directly test the ability of allelochemicals to inhibit mineral absorption by plant cells. 

Inhibition of peroxidation of unsaturated lipid chains in biomembranes is of particular significance and interest, because uncontrolled oxidation disrupts the protective layer around cells provided by the membranes. Furthermore, radical chain transfer reactions can also initiate damage of associated proteins, enzymes and DNA. The volume of literature is immense and expanding in the field of antioxidants. We will select certain milestones of advances where micelles and lipid bilayers, as mimics of biomembranes, provided media for quantitative studies on the activities of phenolic antioxidants. One of us, L. R. C. Barclay, was fortunate to be able to spend a sabbatical in Dr. Keith Ingold s laboratory in 1979-1980 when we carried out the first controlled initiation of peroxidation in lipid bilayers of egg lecithin and its inhibition by the natural antioxidant a-Toc . A typical example of the early results is shown in Figure 4. The oxidizability of the bilayer membrane was determined in these studies, but we were not aware that phosphatidyl cholines aggregate into reverse micelles in non-protic solvents like chlorobenzene, so this determination was not correct in solution. This was later corrected by detailed kinetic and P NMR studies, which concluded that the oxidizability of a lipid chain in a bilayer is very similar to that in homogeneous solution . ... 

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