A review of the unique features of HDL apoproteins

Abstract

The human plasma high density lipoproteins (HDL) are a heterogeneous ensemble of five proteins associated with both neutral and polar lipids. The sequence of all five proteins are known. ApoA-I and apoA-II are the major protein components; apoC-I, apoC-II and apoC-III are the minor protein components. All these apoproteins spontaneously recombine with phospholipids to give stable lipid-protein complexes and freely exchange between the two major HDL subclasses, HDL2 and HDL3. In addition, ApoC-I, apoC-II, and apoC-III exchange between HDL and very low density lipoproteins. Furthermore, certain HDL apoproteins are activators for plasma enzymes that are important in lipid metabolism. ApoA-I and apoC-I activate lecithin/cholesterol acyltransferase; apoC-II is an activator of lipoprotein lipase. The regions of apoC-I and apoC-II that are involved in the activation of these enzymes have been localized with synthetic peptides. Studies of synthetic and native fragments of apoA-II, apoC-I, apoC-II, and apoC-III as well as model lipid-binding peptides have identified specific regions with structural features common to lipid-binding proteins. These special properties, which include helical potential, sequences with a critical amphipathic length, and high hydrophobicity of the nonpolar side of the amphipathic helix, are the determinants of HDL structure and metabolism.