- characteristics
- Structure
- Features
- In the transport and metabolism of cholesterol
- In the binding of lipoproteins to specific factors
- In the immune system
- Other functions
- Related diseases
- References
The apolipoprotein E or ε apolipoprotein, is a plasma apolipoprotein part of the macromolecular complexes known as lipoproteins, which are associated with fats such as triglycerides and cholesterol, which are coated with a layer of phospholipids and other proteins.
This apolipoprotein, as well as other lipoproteins of its same class, contributes to the stabilization and solubilization of lipoproteins (referring to lipoprotein bodies) as they circulate through the bloodstream.
Structure of Apolipoprotein E (Source: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute via Wikimedia Commons)
Due to its participation in lipoproteins, apolipoprotein E has direct implications on the content of cholesterol and triglycerides in serum, which means that it is related to the pathologies associated with the concentration of these lipids in the blood.
Apolipoproteins such as apoE are part of different types of lipoproteins that, depending on their floating density, are classified as chylomicrons, remnant chylomicron particles, very low density lipoproteins (VLDL), intermediate density (IDL), low density (LDL)) and high density (HDL).
Specifically, apolipoprotein E is part of the protein components of chylomicrons, of the remaining chylomicron particles, of VLDL and HDL. It is synthesized in the liver, brain, skin, macrophages, and steroidogenic organs.
characteristics
The protein of 299 amino acids and more or less 34 kDa in molecular weight, is encoded by a gene that belongs to the apolipoprotein genetic family (APO), where each member of the family is composed of units repeated in batches of 11 codons each..
In humans, this highly polymorphic gene has three common alleles and is located on the long arm of chromosome 19, and is closely related to other genes in the same family. It consists of 4 exons and 3 introns that total about 3,597 nucleotides.
Protein is synthesized primarily in liver tissue, but can also be found in the brain, spleen, kidneys, gonads, and macrophages.
The patterns of the different isoforms that it can present are not only genetically determined, but are also due to the presence of post-translational modifications such as the addition of portions of sialic acid (sialylation).
The occurrence of some isoforms with respect to others has been implicated in some pathological conditions, despite the fact that the differences between them are often as simple as amino acid substitutions.
Structure
Like the other apolipoproteins, apolipoprotein E has a highly ordered structure. It is composed of alpha helices, which is predicted from the analysis of its amino acid sequence and verified by experimental methods.
It has a large lipid-binding domain close to the carboxyl terminal end and is secreted with a large amount of sialic acid residues, which are progressively removed through complex mechanisms.
Features
The primary function of apolipoprotein E, as well as many other apolipoprotein variants, is to maintain the structural integrity of lipoproteins in lipid metabolism.
It functions as a cofactor in the enzymatic reactions that take place in lipoprotein spherical bodies and can serve as a surface receptor on these. Specifically, apolipoprotein E is crucial for the formation of very low-density lipoproteins (VLDL) and chylomicrons.
In the transport and metabolism of cholesterol
Because the different isoforms of apolipoprotein E act differently with specific cellular receptors for lipoproteins, they play a fundamental role in regulating and maintaining circulating cholesterol levels.
The apolipoprotein E present in chylomicrons, in the remaining chylomicron particles (after hydrolysis of the triglycerides in their interior) and in very low-density particles is associated with specific receptors that transport them to the liver tissue for cholesterol redistribution or elimination.
It is a determining protein for cellular “uptake” of both HDL and VLDL lipoproteins and in neonates, HDL lipoproteins with apoE are the most abundant.
In the binding of lipoproteins to specific factors
ApoE-containing lipoproteins have the ability to bind to heparin through the same region, by which these particles bind to receptors, which appears to have physiological implications for the binding of lipoproteins to endothelial surfaces.
In the immune system
The surface of lymphocytes (cells of the immune system) has an immunoregulatory receptor capable of specifically binding to apolipoprotein E, rendering the lymphocytes resistant to mitogenic stimulation. This translates into the inhibition of the early transformation events required for the activation of these cells.
Other functions
ApoE and its isoforms have been found to have a major impact on longevity and aging.
Related diseases
More than a million people die each year in the United States due to cardiovascular disease, including coronary heart disease, heart arrhythmias, arterial disease, cardiomyopathies, birth defects, and vascular conditions, among others.
Coronary diseases are the most common, and among the risk factors indicated for these are cigarette consumption, exaggerated cholesterol levels (associated with both excess low-density particles and defects in the amount of high-density particles), hypertension, sedentary lifestyle, obesity and diabetes.
Different studies have shown that defects in the coding locus for apolipoprotein E and its variants correspond to 6% to 40% of the risk factors for coronary heart disease, since they are directly involved in lipid and cholesterol metabolism.
Other diseases with which apoE has been associated have to do with neurological disorders such as Alzheimer's disease, which are associated with the apoE4 variant as a risk factor for the cognitive decline that occurs during the development of this disease.
ApoE apparently interacts with the beta amyloid peptide, whose deposition in the form of amyloid plaques is essential for the establishment of Alzheimer's disease.
References
- Chen, J., Li, Q., & Wang, J. (2011). Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. PNAS, 108 (15744), 2-7.
- Danesh, J. (2009). Major Lipids, Apolipoproteins, and Risk of Vascular Disease. American Medical Association, 302 (18), 1993–2000.
- Eichner, JE, Dunn, ST, Perveen, G., Thompson, DM, & Stewart, KE (2002). Apolipoprotein E Polymorphism and Cardiovascular Disease: a HuGE Review. American Journal of Epidemiology, 155 (6), 487–495.
- Hatters, DM, Peters-libeu, CA, & Weisgraber, KH (2006). Apolipoprotein E structure: insights into function. Trends in Biochemical Sciences, 31 (8), 445-454.
- Mahley, RW, Innerarity, TL, Rall, SC, & Weisgarber, KH (1984). Plasma lipoproteins: apolipoprotein structure and function. Journal of Lipid Research, 25, 1277–1294.
- Raber, J. (2008). AR, apoE, and cognitive function. Hormones and Behavior, 53, 706–715.