VESICULAR MEMBRANE-PERMEABILITY OF MONOMETHYLARSONIC AND DIMETHYLARSINIC ACIDS

The transmembrane permeability coefficients of the environmentally sen sitive arsenicals, monomethylarsonic acid (MMA) and dimethylarsinic ac id (DMA) have been measured for egg phosphatidylcholine large unilamel lar vesicles. The determination of the vesicle concentration-independe nt first-order rate constants for membrane transport and the permeabil ity coefficients were made using an NMR technique employing shift agen ts. The permeability coefficient of DMA was found to be two orders of magnitude greater than that of MMA. This is attributed to the presence of MMAs extra hydroxyl group. Both species are shown to permeate memb ranes in the neutral form. Both the temperature dependence and the dep endence on cholesterol content were investigated for DMA. The activati on energy and the Arrhenius preexponential factor were found to be dep endent on the cholesterol content. A marked increase in both parameter s was observed up to 20 mol.% cholesterol, with a further, small incre ase up to 60%, The significance of these results to our understanding of membrane transport is discussed. The importance of using permeabili ty coefficients rather than n-octanol/water partition coefficients in determining bioavailability and bioaccumulation of environmentally sen sitive compounds is also discussed. (C) 1998 Elsevier Science B.V.