Cholesterol-phospholipid interactions

MD simulations have provided a unique molecular description of cholesterol-phospholipid interactions [31]. Atomistic simulations have succeeded in reproducing the condensing effect of cholesterol on phospholipid bilayers [32-34], With atomistic detail, many properties can be determined, such as the effect of cholesterol on lipid chain ordering or on hydrogen bond formation. Other simulations have focused on the interaction of cholesterol and SM [35-37], Aittoniemi et al. [38] showed that hydrogen bonding alone cannot explain the preferential interaction between cholesterol and SM compared to cholesterol and POPC. 

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McMullen, T.P.W., Lewis, R.N.A.H., McElhaney, R.N. Cholesterol-phospholipid interactions, the liquid-ordered phase and lipid rafts in model and biological membranes. Curr. Opin. Colloid Interface Sci. 2004, 8, 459-68. 

Iscoms (Immune-stimulating complexes) are stable complexes of cholesterol, phospholipid, and Quil A (derived from Quillaja saponaria) in size ranges from 40 to lOOnm. They are promising carriers for antigens in subunit vaccines. Iscoms are considered to be multi-micellar structures, shaped and stabilized by hydro-phobic interactions, electrostatic repulsion, steric factors and possibly hydrogen bonds. Protection... 

The Rho family GTPase Cdc42 directly interacts wilh/l/lC /l / to control filopodia formation, actin organization, and intracellular lipid transport (Diederich et al. 2001 Tsukamoto et al. 2001). We have previously shown (Drobnik et al. 2002) that ABCAl and Cdc42 were partially localized in Lubrol- but not in Triton-X DRMs and that apoA-I preferentially depleted unesterified cholesterol/phospholipids from Lubrol DRMs, whereas HDL3 additionally decreased the cholesterol content of Triton-X DRMs. 

Net transfer of lipid occurs from the plasma to the erythrocyte membrane, presumably because of a shift in the equihbrium as the plasma lipoproteins become saturated with the excess cholesterol and phosphatidylcholine. This leads to membrane abnormalities and cholesterol-phospholipid ratios of up to 2 1. Changes in cellular physiology of the type referred to in section IV have also been reported [94,96,161]. These must reflect an alteration in lipid-protein interactions within the membranes. The molecular arrangement of the excessive amounts of cholesterol present in the cell membranes in diseased liver cells is not known. In model systems cholesterol is not present in molar amounts greater than 1 1. In liver disease a major change is in cellular morphology with the formation of abnormally shaped erythrocytes, as discussed earlier. 

The interaction of HDL with the lipid droplets has been further investigated by morphological methods (Fig. 3). Upon lipid accumulation in the macrophage, an intimate contact between the endoplasmic reticulum (ER) and the margin of the lipid droplet can be observed. At the site of contact, due to the induction of phospholipid and apolipoprotein synthesis, lamellar bodies are formed which are surrounded by a newly synthesized membrane. These lamellar bodies consist of free cholesterol, phospholipids, and apolipoproteins including Apo E. From these lamellar bodies, HDL take up cholesterol, Apo E, and phosphoUpids on their route through the cell (Fig. 3b). In the absence of HDL, the lamellar bodies which originate from cytoplasmic lipid droplets, cannot be secreted from the cell. 

Cholesterol is found abundantly in animal plasma membranes, and the specific interaction of cholesterol with lipid bilayers in an important biological topic. It appears that cholesterol derivatives interact specifically with ammonium bilayers as well. In the hydrolysis of phenyl esters, cholest-Im showed an especially high reactivity when bound to the 2C] 2N 2C bilayer(18). Cholic acid-derived nucleophiles showed normal reactivity patterns, as may be expected from the fact that cholic acid tends to disintegrate the phospholipid bilayer. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

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