Lipoproteins Composition Structure Function and Lipid Transport

A proper balance between phospholipids and free cholesterol (FC) is required to maintain optimal cell membrane structure and fluidity.9 Many cells maintain their FC membrane requirements through endogenous biosynthesis. Other cells, including both the macrophages and underlying SMC involved in atherosclerotic lesion formation, acquire cholesterol by internalization of FC from lipoproteins. Because of their poor water-solubility, neutral lipids such as triglycerides (TGs), FC, and cholesteryl ester generally are not freely circulating in plasma, but instead are packaged together and assembled into larger lipoprotein particles that have amphipathic lipids and proteins as surface components. These submicroscopic spherical particles contain phospholipid (PL) and FC in the outer layer surrounding a core of neutral lipids, primarily cholesteryl ester and TG, held together by noncovalent forces. The cholesteryl ester found in the lipoprotein core is typically derivatized by saturated fatty acids, such as myristate, while the triglycerides contain mixed esters of saturated, unsaturated, and polyunsaturated fatty acids. The proteins associated with the particle surface are known as apolipoproteins (apo), and they control the structural integrity, functionality, and scavenger receptor binding of lipoprotein particles. These apolipoproteins also act as cofactors or inhibitors for remodeling lipases and other enzymes.

Lipoprotein particles have traditionally been classified by their relative density following isolation by ultra-centrifugation and by the type of accompanying primary associated apolipoproteins. As summarized in Table 1, there are six major subtypes of lipoproteins: very low-density lipoproteins (VLDL) and chylomicrons are the largest and least dense of the lipoproteins whose cores are enriched in TG; LDL and HDL are the smallest, densest particles whose cores are enriched in cholesteryl ester; remodeling of VLDL by lipoprotein lipase (LpL) produces intermediate-density lipoprotein (IDL) and then LDL; and lastly, remodeling of LDL produces an LDL-like particle, lipoprotein(a) (Lp(a)). Each of these classes represents a heterogeneous population of particles that vary by their relative size, shape, charge, density, lipid composition, and associated secondary proteins (e.g., apoC-(I, II, III), apoD, apoE).

Table 1 Size and density characteristics of the major classes of lipoproteins and their associated apolipoproteins

Lipoprotein

Origin

Structural

Secondary apolipoproteins

Average diameter Average density

Chylomicrons

VLDL10 IDL

LDL1213 HDL15

Intestine

Liver

Remodeling of VLDL

Liver

Liver, intestine, plasma apoB-48

apoB-100

apoB-100

apoB-100 apoA-I, apoA-II

apoA-I, apoA-II, apoC-I, apoC-II, apoC-III, apoE, apoH

apoC-I, apoC-II, apoC-III, apoE

apoC-III, apoE

apoE

apoA-I, apoA-II, apoC-I, apoC-II, apoC-III, apoD, apoE

>100

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