Keukens E A, de Vrije T, Fabrie C H, Demel R A, Jongen W M, de Kruijff B
Agrotechnological Research Institute (ATO-DLO), Wageningen, Netherlands.
Biochim Biophys Acta. 1992 Oct 5;1110(2):127-36. doi: 10.1016/0005-2736(92)90349-q.
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.
在本研究中，通过渗透性测量和不同的生物物理方法，分析了糖苷生物碱α-茄碱、α-查茄碱、α-番茄碱以及苷元茄啶在有无甾醇存在的情况下对由磷脂酰胆碱（PC）组成的模型膜的影响。主要结果是，糖苷生物碱能够与含甾醇的膜强烈相互作用，从而以一种对糖苷生物碱和甾醇类型具有特异性的方式导致膜破坏。对于这种双重特异性，糖苷生物碱的糖部分和甾醇在24位的侧链对膜破坏活性至关重要。糖苷生物碱的效力顺序为α-番茄碱>α-查茄碱>α-茄碱。与胆固醇和麦角固醇相比，植物甾醇β-谷甾醇和岩藻甾醇对糖苷生物碱表现出更高的亲和力。糖苷生物碱的作用模式被认为包括三个主要步骤：（1）苷元部分插入双层膜中。（2）糖苷生物碱与存在的甾醇形成复合物。（3）由甾醇 - 糖苷生物碱复合物网络的形成导致膜重排，从而导致双层膜的短暂破坏，在此期间发生泄漏。
