2.1. Plasma lipids and lipoproteins
Lipids play very important roles in maintaining the structure of cell membrane (cholesterol, phospholipids), cell growth (cholesterol), steroid hormone synthesis (cholesterol), and energy metabolism (triglycerides). Since lipids are highly hydrophobic, they have to be packed into lipoproteins as water-soluble particles in blood circulation (Gotto et al. 1986). A lipoprotein is a particle consisting of a core of hydrophobic lipids, i.e., triglycerides (TG), cholesteryl esters (CE), surrounded by a polar layer of phospholipids (PL), unesterified cholesterol (FC), and apolipoprotein(s) (Ginsberg 1990). Plasma lipoproteins are usually classified into five major subfractions based on their density (d), particle size, flotation rate (Sf), and electrophoretic mobility in agarose gel. Routinely, the lipoproteins are separated by sequential ultracentrifugation (Havel et al. 1955).
Table 1. Properties and apolipoprotein composition of the major human plasma lipoproteins
CMs are derived from dietary lipids (exogenous pathway) and assembled in the intestinal epithelial cells. TGs are the major constituents of the CM particles. The TGs in CM are hydrolyzed in the peripheral tissues by lipoprotein lipase (LPL) to form the CM remnants which are taken up by the liver in a process that probably involves apolipoprotein E (apoE) on the surface of the remnants and a hepatic receptor called LDL receptor-related protein (LRP) (Beisiegel 1995). VLDL particles are synthesized in the liver (endogenous pathway). They are the main liver-derived TG-rich lipoproteins and in circulation, their TGs are hydrolyzed by LPL and the VLDLs are then degraded into CE-enriched particles called IDL (Gotto et al. 1986). About half of the IDL particles are taken up by the liver via LDL receptor and remnant receptor (van Berkel et al. 1995), whereas the other half are converted into LDL by hepatic lipase (HL) (Taskinen and Kuusi 1987). LDLs are the major carriers of cholesterol in plasma. LDL metabolism is discussed in more detail in Section 2.2.2. Lipoprotein (a) [Lp(a)], which consists of an LDL particle covalently attached to apolipoprotein (a) [apo(a)], is a distinct class of CE-rich plasma lipoprotein. It can bind weakly to LDL receptors and play a role in the genesis of atherosclerosis (Jauhiainen et al. 1991).
HDLs consist of apoAI and apoAII as the main apolipoprotein constituents and carry about 20% cholesterol, most of which are CE (Ginsberg 1990). HDLs are synthesized in the liver and intestine (Franceschini et al. 1991). Also HDLs can be generated following the lipolysis of TG-rich lipoproteins whereafter plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and some cholesterol into HDL pool (Eisenberg 1984, Jiang et al. 1999). In addition, the lecithin-cholesterol acyltransferase (LCAT) has a crucial role in the maturation of HDL particles. LCAT can catalyze the formation of CE which are then incorporated into the core of discoidal nascent HDL (Franceschini et al. 1991). HDLs (especially preß-mobile HDL) play a major role in the transport of cholesterol from peripheral tissues to the liver, a process known as reverse cholesterol transport (Tall 1990). HDL CE are transfered by cholesteryl ester transfer protein (CETP) to apoB-containing particles which are finally removed from the circulation by the liver (Tall 1993). In addition, HDLs can be taken up by class B scavenger receptor (SR-BI)-mediated process in certain cells where this receptor mediates selective CE uptake leaving the HDL particles largely intact (Acton et al. 1996, Krieger 1998), or directly removed by the liver (Tall 1992).
