Effect of alkyl-substituted precursors of cholesterol on artificial and natural membranes and on the viability of Mycoplasma capricolum

Various alkyl-substituted sterols and stanols representative of the intermediates in cholesterol biosynthesis from lanosterol have been compared with respect to (a) their effect on the physical state of lecithin vesicles, (b) their efficacy as growth factors for the sterol auxotroph Mycoplasma capricolum, and (c) their effect on the physical state of the respective mycoplasma membranes. By all three criteria, sterol effectiveness progresses in the order lanosterol less than 4,4-dimethylcholestanol less than or equal to 4 beta-methylcholestanol less than 4 alpha-methylcholestanol less than cholestanol less than cholesterol. Since the corresponding steps in cholesterol biosynthesis occur in the same order, we conclude that the nuclear modifications of the lanosterol structure by oxidative demethylation serve to improve the membrane function of the sterol molecule.