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Apolipoprotein E (Apo E)

Circulating human apoE (apolipoprotein E) is a single-chain protein of 34.2 kDa, encoded by single gene. ApoE is initially synthetised as a propeptide of 317 amino acid residues. After post-translational cleavage of a signal peptide of 18 amino acids, the mature protein consists of 299 amino acids. The human apoE gene is polymorphic, with three common alleles (epsilon2, epsilon3, epsilon4) coding for three isoforms (E2, E3, E4). The molecular basis of this polymorphism is cystein-arginine interchange. This polymorphism leads to the presence of six different phenotypes in the human population: three homozygous and three heterozygous. ApoE is produced in various organs, including kidney, adrenal glands, gonads and spleen, but mainly in liver. The second largest production of ApoE is found in the brain. It has many functions in the body. When it is synthetised by the liver as part of VLDL it functions in the transport of triglycerides to the liver tissue. It is incorporated into HDL (as HDL-E) and functions in cholesterol distribution among cells. It is also incorporated into intestinally synthetised chylomicrons and transports dietary triglycerides and cholesterol. ApoE is involved in lipid metabolism by mediating the receptor binding of apoE lipoproteins to the LDL receptor. Other functions and properties ascribed to apoE include its role in immunoregulation, inflammatory response, nerve regeneration, inhibition of endothelial and tumor cell proliferation. ApoE plays a significant role in the pathogenesis of atherosclerosis. One of the functions suggested for apoE is based on observations that apoE is found in amyloid plaques associated with Alzheimer´s and Creutzfeldt-Jakob diseases, as well as in a variety of types of cerebral and systemic amyloidoses.

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