Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, (INIFTA-CCT La Plata-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CC 16, Sucursal 4 1900 - La Plata, Argentina.
Biochimie. 2012 Jan;94(1):101-9. doi: 10.1016/j.biochi.2011.09.025. Epub 2011 Oct 5.
The "Fluid Mosaic Model", described by Singer and Nicolson, explain both how a cell membrane preserves a critical barrier function while it concomitantly facilitates rapid lateral diffusion of proteins and lipids within the planar membrane surface. However, the lipid components of biological plasma membranes are not regularly distributed. They are thought to contain "rafts" - nano-domains enriched in sphingolipids and cholesterol that are distinct from surrounding membranes of unsaturated phospholipids. Cholesterol and fatty acids adjust the transport and diffusion of molecular oxygen in membranes. The presence of cholesterol and saturated phospholipids decreases oxygen permeability across the membrane. Alpha-tocopherol, the main antioxidant in biological membranes, partition into domains that are enriched in polyunsaturated phospholipids increasing the concentration of the vitamin in the place where it is most required. On the basis of these observations, it is possible to assume that non-raft domains enriched in phospholipids containing PUFAs and vitamin E will be more accessible by molecular oxygen than lipid raft domains enriched in sphingolipids and cholesterol. This situation will render some nano-domains more sensitive to lipid peroxidation than others. Phospholipid oxidation products are very likely to alter the properties of biological membranes, because their polarity and shape may differ considerably from the structures of their parent molecules. Addition of a polar oxygen atom to several peroxidized fatty acids reorients the acyl chain whereby it no longer remains buried within the membrane interior, but rather projects into the aqueous environment "Lipid Whisker Model". This exceptional conformational change facilitates direct physical access of the oxidized fatty acid moiety to cell surface scavenger receptors.
辛格和尼科尔斯提出的“流动镶嵌模型”,既解释了细胞膜如何在保持关键屏障功能的同时促进蛋白质和脂质在平面膜表面的快速横向扩散,也解释了细胞膜脂质成分并非均匀分布的原因。人们认为这些脂质成分包含富含鞘脂和胆固醇的“筏”(nano-domains),它们与周围不饱和磷脂的膜不同。胆固醇和脂肪酸调节着分子氧在膜中的运输和扩散。胆固醇和饱和磷脂的存在会降低分子氧通过膜的通透性。生物膜中主要的抗氧化剂α-生育酚(alpha-tocopherol)会分配到富含多不饱和磷脂的区域,从而增加维生素在最需要的地方的浓度。基于这些观察结果,可以假设富含多不饱和脂肪酸(PUFAs)和维生素 E 的非筏区域比富含鞘脂和胆固醇的脂质筏区域更容易被分子氧进入。这种情况将使一些纳米区域比其他区域更容易受到脂质过氧化的影响。磷脂氧化产物很可能会改变生物膜的性质,因为它们的极性和形状可能与母分子的结构有很大的不同。向几个过氧化脂肪酸中添加一个极性氧原子会重新定向酰基链,使其不再埋在膜内部,而是突入水性环境中“脂质须模型”。这种特殊的构象变化促进了氧化脂肪酸部分与细胞表面清道夫受体的直接物理接触。