Sterol molecular modifications influencing membrane permeability

Various sterols and related steroids were tested for their ability to influence ethanol-induced electrolyte leakage from Hordeum vulgare roots. Cholesterol had the greatest influence and, depending on concentration, it stimulated or inhibited the loss of electrolyte. Cholesterol, however, was ineffective if the roots were pretreated with ethanol. These data suggest that sterols protect rather than restore membrane structure. First, modifications in the cholesterol perhydrocyclopentanophenanthrene ring system suggest that at least one double bond is required for membrane activity. Second, increasing the bulkiness of the C(17) side chain of cholesterol, as shown with campesterol, stigmasterol, and sitosterol, decreased its activity. Apparently for maximum effectiveness the sterol molecule should have a relatively flat configuration. Third, the C(3)-hydroxyl group is required for membrane activity since cholesteryl methyl ether, cholest-5-ene-3beta-thiol and cholesteryl halogens were without activity. Exception to the foregoing rule was cholestane which was slightly active but which has neither a C(3)-hydroxyl group nor a double bond in the ring system.