Cholesterol exchange between lipoproteins

B10. Barter, P. J., Hopkins, G. J., Gorjatschko, L., and Jones, M. E., A unified model of esterified cholesterol exchanges between human plasma lipoproteins. Atherosclerosis 44, 27-40 (1982). 

Steck TL, Ye J, Lange Y. Probing red cell membrane cholesterol movement with cyclodextrin. Biophys. J. 2002 83 2118-2125. Estronca LMBB, Moreno MJ, Laranjinha JAN, Almeida LM, Vaz WLC. Kinetics and thermodynamics of lipid amphiphiles exchange between lipoproteins and albumin in serum. Biophys. J. 2005 88 557-565. 

Sniderman, A., Teng, B., Vezina, C., and Marcel, Y. L., Cholesterol ester exchange between human plasma high and low density lipoproteins mediated by a plasma protein factor. Atherosclerosis 31, 327-333 (1978). 

In blood, unesterified or free cholesterol experiences countless exchanges among the following blood components [17] (i) between lipoproteins of the same or different types, (ii) between plasma membranes and all types of lipoproteins, and (iii) between red cells and various lipoproteins. These cholesterol exchanges among various lipoprotein species are extremely rapid because they involve transfer of cholesterol molecules mostly situated at the surface of lipoprotein complexes. On the other hand, the exchange rates of cholesterol esters among lipoproteins are much slower. This is because transfer of the cholesterol ester molecule between two lipoprotein complexes must involve first the exit of the ester molecule from the nonpolar core of one... 

The rate of bidirectional transfers of esterified cholesterol between human plasma LDL and HDL in vitro ranges from 100 to 300 nmol/hour per milliliter of plasma, representing an hourly exchange of 8-12% of LDL and 7-31% of HDL esterified cholesterol (B12). As the rates of catabolism in vivo of human LDL and HDL apoprotein are 1-2% and less than 1% per hour, respectively (B41, L4), it is apparent that the residence time in plasma of human LDL and HDL is such that these lipoproteins in vivo may achieve a virtually complete equilibration of esterified cholesterol. However, as pointed out in a review by Barter et al. (B7), the residence time in plasma of human VLDL is such that equilibration of esterified cholesterol with VLDL [which in vitro requires 5-8 hours of incubation at 37°C (H31)] is incomplete in vivo. 

B16. Barter, P. J., and Lally, J. I., In vitro exchanges of esterified cholesterol between serum lipoprotein fractions Studies of humans and rabbits. Metabolism 28, 230-236 (1979). 

Human lipoproteins exist in several sizes and densities with differing lipid to protein ratios. These various lipoproteins have different origins in the body, different destinations and different functions (10). Thus, chylomicrons are extremely large low density particles formed in the intestine and designed to deliver dietary fat to adipose tissue. Very low density lipoproteins (VLDL), on the other hand, are smaller, more dense particles designed to deliver lipids from the liver to adipose and other tissues. Low density lipoproteins (LDL), formed from VLDL or produced in the liver or intestine deliver cholesterol to peripheral tissue, while high density lipoproteins (HDL) function to return cholesterol from peripheral tissues to the liver for catabolism. There is a complex exchange of lipids and apoproteins between the lipoprotein classes. 

Each newly synthesized intestinal apo B-containing lipoprotein particle (chylomicron) consists of a core lipid droplet rich in TG, surrounded by a monolayer made up mainly of protein, phospholipids, and cholesterol. The chylomicron lipid core contains a small amount of CE. The lipids of TG-rich particles are in a dynamic equilibrium where each lipid can exchange rapidly between the surface and core. As a result, while the great majority of TG is in the core, the surface contains a small but rapidly replenished pool ofTG which is the direct substrate of the plasma lipases responsible for chylomicron metabolism in the circulation. 

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. 

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