Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation

https://science.sciencemag.org/content/sci/240/4852/622.full.pdf

Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

Plasma lipoproteins: apolipoprotein structure and function.

The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function.

Publisher Summary This chapter focuses on the role of apoE in lipoprotein metabolism and the most completely described function of the protein. Apolipoprotein E (apoE) is one of the best characterized in terms of its structural and functional properties. Plasma apolipoproteins regulate lipoprotein metabolism and control the transport and redistribution of lipids among tissues and cells. Apolipoproteins can perform one of three major roles because of their ability to bind lipid. First, apolipoproteins stabilize the pseudomicellar structure of lipoprotein particles. Second, apolipoproteins can act as cofactors or activators of various enzymes or lipid transfer proteins that participate in the metabolism of “remodeling” of lipoproteins as they circulate in plasma. A third function of plasma apolipoproteins-one that is restricted to apoB100 and ApoE- is to serve as a ligand for cell surface lipoprotein receptors. The three-dimensional structure of a 22-kDa fragment of human apoE is solved by X-ray crystallography; the relation of this structure to the role of apoE in lipoprotein metabolism is discussed, together with a critical and extensive examination of the chemistry and biology of this apolipoprotein, which plays such a central role in lipoprotein metabolism. Apolipoprotein E has three major isoform in the human population, which affect lipoprotein metabolism differently, resulting in different levels of the plasma lipoproteins. The role of apoE as a cofactor in lipolytic processing of triglyceride-rich lipoproteins, and the role of apoE in the reverse cholesterol transport process are described.

Apolipoprotein E: Structure-Function Relationships

Polyunsaturated Fatty Acid Families and Interrelationships Omega-6 Fatty Acids and Plasma Lipids Plasma Cholesterol Plasma Triglycerlde Plasma LJpoprotelns and Apolipoproteins Hypolipldemic Mechanisms of Linoleic Acid Decrease in Cholesterol Absorption Increase in Fecal Steroid Excretion Reduced Cholesterol Synthesis and the Transfer of Cholesterol to the Tissues Decrease in Cholesterol Content of LJpoproteins Changes in the Rates of Synthesis and Catabolism of LJpoproteins Membrane Fatty Acid Composition and Upoprotein Metabolism

Polyunsaturated fatty acids, hyperlipidemia, and thrombosis.

The human plasma apoproteins apoA-I and apoC-I enhanced the activity of partially purified lecithin: cholesterol acyltransferase five to tenfold with chemically defined phosphatidylcholine:cholesterol single bilayer vesicles as substrates. By contrast, apoproteins apoA-II, apoC-II, and apoC-III did not give any enhancement of enzyme activity. The activation by apoA-I and apoC-I differed, depending upon the nature of the hydrocarbon chains of phosphatidylcholine acyl donor. ApoA-I was most effective with a phosphatidylcholine containing an unsaturated fatty acyl chain. ApoC-I activated LCAT to the same extent with both saturated and unsaturated phosphatidylcholine substrates. Two of the four peptides obtained by cyanogen bromide cleavage of apoA-I retained some ability to activate LCAT. The efficacy of each of these peptides was approximately 25% that of the whole protein. Cyanogen bromide fragments of apoC-I were inactive. The apoproteins from HDL, HDL2, and HDL3, at low protein concentrations, were equally effective as activators of LCATand less effective than apoA-I. Higher concentrations of apoHDL, apoHDL2, and apoHDL3 inhibited LCAT activity. ApoC and apoA-II were both found to inhibit the activation of LCAT by apoA-I. The inhibition of LCAT by higher concentrations of apoHDL was not correlated with the aopA-II and apoC content.

Richard L Jackson

Papers

Effect of the human plasma apolipoproteins and phosphatidylcholine acyl donor on the activity of lecithin: cholesterol acyltransferase.

Quantification of apoC-II and apoC-III of human very low density lipoproteins by analytical isoelectric focusing

BRIEF REVIEWS The Role of Dietary Polyunsaturated Fat in Lowering Blood Cholesterol in Man

Mechanism of lipid-protein interaction in the plasma lipoproteins: lipid-binding properties of synthetic fragments of apolipoprotein A-II.

Isolation and characterization of the cyanogen bromide fragments from the high-density apolipoprotein glutamine I.