title: Dual specificity of sterol-mediated glycoalkaloid induced membrane disruption.
abstract: In this study the effects of the glycoalkaloids alpha-solanine, alpha-chaconine, alpha-tomatine and the aglycone solanidine on model membranes composed of PC in the absence and presence of sterols have been analysed via permeability measurements and different biophysical methods. The main result is that glycoalkaloids are able to interact strongly with sterol containing membranes thereby causing membrane disruption in a way which is specific for the type of glycoalkaloid and sterol. For this dual specificity both the sugar moiety of the glycoalkaloid and the side-chain of the sterol on position 24 turned out to be of major importance for the membrane disrupting activity. The order of potency of the glycoalkaloids was alpha-tomatine > alpha-chaconine > alpha-solanine. The plant sterols beta-sitosterol and fucosterol showed higher affinity for glycoalkaloids as compared to cholesterol and ergosterol. The mode of action of the glycoalkaloids is proposed to consist of three main steps: (1) Insertion of the aglycone part in the bilayer. (2) Complex formation of the glycoalkaloid with the sterols present. (3) Rearrangement of the membrane caused by the formation of a network of sterol-glycoalkaloid complexes resulting in a transient disruption of the bilayer during which leakage occurs.
authors.affiliation: Agrotechnological Research Institute (ATO-DLO), Wageningen, Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Keukens
authors.forename: T
authors.initials: T
authors.lastname: de Vrije
authors.forename: C H
authors.initials: CH
authors.lastname: Fabrie
authors.forename: R A
authors.initials: RA
authors.lastname: Demel
authors.forename: W M
authors.initials: WM
authors.lastname: Jongen
authors.forename: B
authors.initials: B
authors.lastname: de Kruijff
mesh_terms: D002152:Calorimetry, Differential Scanning; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004144:Diosgenin; D005614:Freeze Fracturing; D008051:Lipid Bilayers; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D012992:Solanine / Q000031:analogs & derivatives / Q000494:pharmacology; D013261:Sterols / Q000378:metabolism*; D013379:Substrate Specificity; D014053:Tomatine / Q000494:pharmacology
chemical_list: D008051:Lipid Bilayers; D012991:Solanaceous Alkaloids; D013261:Sterols; D012992:Solanine; C011860:alpha-chaconine; D014053:Tomatine; D004144:Diosgenin; C013255:solanidine