phytosterols and 7-dehydrocholesterol

The selectivity of the antibiotic nystatin towards ergosterol compared to cholesterol is believed to be a crucial factor in its specificity for fungi. In order to define the structural features of sterols that control this effect, nystatin interaction with ergosterol-, cholesterol-, brassicasterol- and 7-dehydrocholesterol-containing palmitoyloleoylphosphocholine vesicles was studied by fluorescence spectroscopy. Variations in sterol structure were correlated with their effect on nystatin photophysical and activity properties. Substitution of cholesterol by either 7-dehydrocholesterol or brassicasterol enhance nystatin ability to dissipate a transmembrane K+ gradient, showing that the presence of additional double bonds in these sterols-carbon C7 and C22, plus an additional methyl group on C-24, respectively-as compared to cholesterol, is fundamental for nystatin-sterol interaction. However, both modifications of the cholesterol molecule, like in the fungal sterol ergosterol, are critical for the formation of very compact nystatin oligomers in the lipid bilayer that present a long mean fluorescence lifetime and induce a very fast transmembrane dissipation. These observations are relevant to the molecular mechanism underlying the high selectivity presented by nystatin towards fungal cells (with ergosterol) as compared to mammalian cells (with cholesterol).

Topics: Cholestadienols; Cholesterol; Dehydrocholesterols; Ergosterol; Kinetics; Liposomes; Nystatin; Permeability; Phosphatidylcholines; Phytosterols; Spectrometry, Fluorescence; Sterols

Steinernema feltiae (= Neoaplectana carpocapsae), 'All' strain, was propagated in larvae of the corn earworm, Heliothis zea, which contained various sterols, in order to determine how the sterol composition of the host affects the growth, development and sterol composition of this insect-parasitic nematode. S. feltiae completed its life cycle normally in insects containing primarily cholesterol, cholestanol or 7-dehydrocholesterol, although the sterol composition of the dauer stage was affected by the sterol composition of the host. When the nematode was reared in insects containing primarily cholesterol, 55% of the sterol in the dauers was cholesterol and the other 46% was lathosterol. In contrast, cholestanol (70%) and lathostetrol (31%) were the sterols present in nematodes reared in H. zea containing primarily cholestanol. Cholestanol (43%), lathosterol (34%), campestanol and/or another 24-methylsterol (23%) and cholesterol (1%) were the sterols present in nematodes reared in H. zea containing campestanol and cholestanol as its major sterols. Lathosterol was the major sterol present in nematodes reared in H. zea containing principally 7-dehydrochlesterol. Therefore, in each case, S. feltiae metabolized some host sterol to lathosterol but the relative percentage of lathosterol in the nematode increased as it was exposed to delta 0-, delta 5- and delta 5,7-sterols, respectively. The ability of S. feltiae to utilize different host sterols may, in part, explain its success in parasitizing a wide variety of insects.

Topics: Animals; Cholestanols; Cholesterol; Dehydrocholesterols; Female; Host-Parasite Interactions; Larva; Lepidoptera; Male; Nematoda; Phytosterols; Sterols

To determine the role of the ring structure in the differential absorption of sterols, we have used rat jejunal brush border vesicles and erythrocytes to examine the uptake of cholesterol, campesterol, and sitosterol following successive chemical degradations of rings A and B. The cell and membrane preparations were incubated with the sterols and sterol analogues (about 30 micromolar each) dissolved in 7 mM sodium taurocholate and 0.6 mM egg phospholipid. The uptake of the analogues was analyzed by high performance liquid chromatography and capillary gas--liquid chromatography. In both membrane preparations, the uptake of the 7-dehydroanalogues of cholesterol, campesterol, and sitosterol was linear with time. 7-Dehydrocholesterol was absorbed 4-5 times faster than 7-dehydrositosterol by both preparations. The uptake of the campesterol analogue was intermediate between that of the analogues of cholesterol and sitosterol at all time points. Following conversion of the 7-dehydrosterols to their calciferol derivatives, the 27-carbon sterols were absorbed only 1.9 and 1.4 times faster than those of the 29-carbon sterols by the erythrocyte and brush border membranes, respectively. A similar degree of selectivity was expressed in the erythrocytes during the uptake of a steroid series possessing keto-4-ene ring system. Complete oxidation of the calciferol derivatives to the des-AB-8-ones resulted in a total loss of discrimination among the various side-chain homologues during absorption from micellar solutions. It is concluded that the selective absorption of animal and plant sterols depends upon the presence of a ring system having the bulk of the cholestane nucleus, although not necessarily a rigid or planar one containing a hydroxyl group.

Topics: Absorption; Animals; Cell Membrane; Cholesterol; Chromatography, High Pressure Liquid; Dehydrocholesterols; Ergocalciferols; Ergosterol; Erythrocytes; Gas Chromatography-Mass Spectrometry; Jejunum; Micelles; Microvilli; Phytosterols; Rats; Sitosterols; Structure-Activity Relationship