Apolipoprotein

The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating a lipoprotein particle that is itself water-soluble, and can thus be carried through body fluids (i.e., blood, lymph).

In addition to stabilizing lipoprotein structure and solubilizing the lipid component, apolipoproteins interact with lipoprotein receptors and lipid transport proteins, thereby participating in lipoprotein uptake and clearance. They also serve as enzyme cofactors for specific enzymes involved in the metabolism of lipoproteins.

Apolipoproteins are also exploited by hepatitis C virus (HCV) to enable virus entry, assembly, and transmission. They play a role in viral pathogenesis and viral evasion from neutralizing antibodies.

Functions

Different lipoproteins contain different classes of apolipoproteins, which influence their function.

Apolipoprotein AI (apoA1) is the major structural protein component of high-density lipoproteins (HDL), although it is present in other lipoproteins in smaller amounts. Apolipoprotein A-IV (apoA4) is present in chylomicrons, very-low-density lipoproteins (VLDL), and HDL. It is thought to act primarily in reverse cholesterol transport and intestinal lipid absorption via chylomicron assembly and secretion. ApoA-IV synthesized in hypothalamus is suggested to be a satiating factor which regulates the food intake of the rodent.

Apolipoprotein B plays a particularly important role in lipoprotein transport being the primary organizing protein of many lipoproteins.

Apolipoprotein C-III (apoC3) plays an important role in lipid metabolism specific in regulating the metabolism of triglyceride-rich lipoproteins (TRLs).

Apolipoprotein D (apoD) is a soluble carrier protein of lipophilic molecules in neurons and glial cells within the central and peripheral nervous system and apoD can also modulate the stability and oxidation status of these molecules.

Apolipoprotein E (apoE) plays an important role in the transport and uptake of cholesterol by way of its high affinity interaction with lipoprotein receptors, including the low-density lipoprotein (LDL) receptor. ApoE is the major lipoprotein in the central nervous system. Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related. The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix.

Apolipoprotein F (apoF) is one of the minor apolipoprotein in blood plasma and it is a lipid transfer inhibit protein to inhibit cholesteryl ester transfer protein-mediated transfers of cholesteryl esters and triglycerides.

Apolipoprotein M (apoM) participates in the lipid metabolism and exhibit anti‑atherosclerotic functions and it is presented in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).