Lipoproteins lipid transfer between

Webb, NR, Connell, PM, Graf, GA, Smart, EJ, de Villiers, WJ, de Beer, FC, and van der Westhuyzen, DR, 1998. SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells. J Biol Chem 273, 15241-15248. 

Two possible mechanisms of lipid transfer between lipoproteins that do not involve proteins are the following. In the first mecha-nism, lipid molecules escape slowly from the lipoprotein surface in the rate-limiting step and are taken up rapidly from the aqueous medium. In the second mechanism, transfer requires the formation of a collision complex of the donor and acceptor lipoproteins that... 

The mechanism of lipid transfer between lipoproteins was demonstrated initially with fluorescent probes (Charlton et al.,... 

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

In humans, CETP and PLTP are directly involved in the transfer of lipids between different lipoprotein classes. Through their action, these lipid transfer proteins have major effects on the concentration and composition of HDL. This section further describes the physiological function of CETP and PLTP in humans. 

It should also be remembered that plasma lipoproteins are constantly in a state of metabolic flux. Some large particles are converted to smaller particles, and vice versa. Lipids and most apolipoproteins exchange or are transferred between particles and particles are released into and removed from the circulation. 

Plasma HDL constitute a heterogeneous group of lipoproteins their common property is that they have a hydrated density in the 1.063-1.21 g/ml interval. HDL subfractions are usually described in terms of their hydrated density, but it should not be forgotten that a number of functions may be the property of particular subsets of HDL which can be defined better in terms of their apolipoprotein composition than their hydrated density. A preparation of HDL isolated by flotation in the ultracentrifuge, d between 1.063 and 1.21 g/ml, may contain almost all the major apolipoproteins (except perhaps apoA-IV and apoB-48), together with LCAT and lipid transfer protein. 

B13. Barter, P. J., and Jones, M. E., Kinetic studies of the transfer of esterified cholesterol between human plasma low and high density lipoproteins. /. Lipid Res. 21, 238-249 (1980). 

C3. Calvert, G. D., and Abbey, M., The isolation and partial characterisation of two lipid transfer proteins (LTP-I and LTP-II), each of which facilitates the transfer of esterified cholesterol, triglyceride and phospholipid between plasma lipoproteins. In "Atherosclerosis VI, Proceedings of the Sixth International Symposium (F. G. Schettler, A. M. Gotto, G. Middelhoff, A. J. R. Habenicht, and K. R. Jurutka, eds.), pp. 428-431. Springer-Verlag, Berlin, 1983. 

Several functions of MTP have been identified all have been implicated in coordinating successful lipoprotein assembly (Fig. 27-1). MTP transfers lipids between vesicles in vitro, and this activity is likely to be its major function. MTP can pick up lipids from membrane (step A) or vesicles and droplets (step B) and transfer them to the nascent apoB. In addition, the lipid transfer activity of MTP has been implicated in the accretion of neutral lipids from the cytosol into the ER lumen (step C). Compounds that inhibit in vitro transfer activity of MTP decrease apoB secretion by cells, indicating that this activity is essential for apoB lipoprotein secretion. Apart from transferring lipids, MTP has been shown to interact physically with apoB (step D). This activity... 

In hepatocytes, vitamin E can take two routes. A fraction of it is packaged as VLDL and reenters the circulation, while excess is excreted in the bile. Plasma lipolysis of the VLDL particle again results in release not only of lipids, but also of vitamin E, with the remainder left with the LDL particles. This fraction can be further distributed to tissues via LDL receptor-mediated endocytosis or transferred between lipoproteins, mainly to HDL, by plasma lipid transfer proteins. Thus, mobilization of vitamin E from intestinal and liver... 

For simplicity of calculation, the core was assumed to contain all of the triglyceride and cholesteryl ester, although it is known that small amounts of the core lipids are dissolved in the surface monolayer, where they represent about 3 mol% of the surface lipids, and a larger fraction, about one ninth of the cholesterol, is dissolved in the core (Miller and Small, 1987). The presence of core lipids in the lipoprotein surface is very important metabolically, for the lipases and transfer proteins have access to these core lipids without having to penetrate the surface monolayer. For the calculation of composition, density, and size, however, the effects of component transfer between surface and core affect these quantities about one part in the fourth significant figure, and have been neglected in Table II. 

Lipoproteins have also been used for studying protein-stimulated phospholipid transfer between lipoproteins (Ihm et al., 1982), and between lipoproteins and vesicles (Damen et al., 1981, 1982). Care must be exercised when high density lipoprotein is used as a substrate in an exchange reaction with vesicles, since vesicles may be disrupted and net transfer of lipid results (Damen et al., 1981). A high density lipoprotein-vesicle assay with appropriate precautions has been employed by Damen et al. (1981). 

Transfer of cholesteryl esters, triglycerides, and phospholipids between lipoproteins by specific lipid-transfer proteins... 

While most of the known functions of apolipoproteins are associated with their lipid-bound states, lipid-free or lipid-poor exchangeable apolipoproteins do exist in plasma and interstitial fluid, and have important metabolic roles in lipid uptake from cells, transfers between lipoproteins, structural remodeling of lipoproteins, and apolipoprotein catabolism. 

The cholesterylesters present on plasma lipoproteins are partly secreted into the plasma on nascent hpoproteins (chylomicrons and VLDL) and partly synthesized by the plasma enzyme LCAT. In some species, including man, active lipid transfer proteins (LTP) circulate in plasma. Both LCAT and LTP are synthesized in the liver (for reviews, see [25, 26]). Cholesterylester transfer protein (CETP) catalyses a transfer/exchange of cholesterylesters between HDL and the other lipoproteins. This process is important for the turnover of plasma cholesterol because, depending on the amount of active CETP and the chemical composition of the circulating plasma hpoproteins, a variable part of the HDL-cholesterylesters are transferred by CETP to hpoprotein classes of lower density, or vice versa. The presence of active CETP seems to provide a link between VLDL/IDL/LDL metabolism on one hand, and HDL metabohsm on the other. In addition LTP may directly influence the hepatic uptake of cholesterylesters from lipoproteins by as yet unknown mechanisms. 

Transfer of intact phospholipids from one cell to another may take place by diffusion as single molecules (below the critical micelle concentration) or as small spherical micelles (d = 70 A) phospholipids form at low concentration in aqueous media. Diffusion may be helped by stirring (as in blood) and by contact between cells. Free acyl chains resulting from attack by lipases may diffuse as individual molecules, or complexed to small proteins such as albumin in blood. Similar modes of transport would apply to lipid exchanges between blood cells and lipoproteins. 

Cholesteryl ester transfer protein (CETP) promotes exchange and transfer of neutral lipids such as cholesteryl ester (CE) and TG between plasma lipoproteins [63-65], The function of CETP is illustrated in Fig. 3. CETP is a very hydrophobic and heat-stable glycoprotein with an apparent molecular weight of 74 kDa as determined by SDS-PAGE analysis [66,67], The cDNA from human liver was cloned and sequenced [68], It encodes for a 476-amino acid protein (53 kDa), suggesting that the apparent higher molecular weight is due to the addition of carbohydrate residues by posttranslational modification. 

---