Enzyme Explorer

Apolipoprotein



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Overview
Classification of Lipoproteins and the Systemic Pathway of Lipids
Apolipoprotein Classification, Properties and Function

Plasma & Blood Protein Resource


Apolipoprotein Classification, Properties and Function

Apolipoprotein Composition of Lipoproteins

  Chylomicron VLDL IDL LDL HDL
Apo-AI (29KD) X       X

Apo-AII (17.4KD) X       X

Apo-AIV (46KD) X       X

Apo-B48 (241KD) X        

Apo-B100 (513KD)   X X X X  

Apo-CI (7.6KD) X X X   X

Apo-CII (8.9KD) X X X   X

Apo-CIII (8.8KD) X X X   X

Apo-D (20KD)         X

Apo-E (34KD) X X X   X

Apo-H (50KD) X        

Apo(a) (300-800KD)       X  

Apolipoprotein AI (Apo-AI), A0722

Apo-AI comprises approximately 70% of the protein moiety in HDL. It is a single polypeptide chain consisting of 245 amino acids with glutamic acid as the C-terminal residue and aspartic acid as the N-terminal residue. The molecular weight is reported to be 28.3 kDa. The protein is made up of one major isoform (pI 5.6) and two minor isoforms (pI 5.53 and 5.46). Apo-AI shows a high content of α-helix structure. The amphipathic regions in the α-helix structure seem to be responsible for lipid binding capacity. In aqueous solution, Apo-AI shows self-association with minor conformation change. Apo-AI activates lecithin-cholesterol (LCAT) acyltransferase, which is responsible for cholesterol esterification in plasma.

Apo-AI levels in normal plasma are 90-130 mg/dl. Apo-AI levels may be inversely related to the risk of coronary disease.

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Apolipoprotein AII (Apo-AII), A0972

The function of Apo-AII is unclear. Apo-AII comprises 25% of Apo A in HDL. Apo-AII levels in normal plasma are 30-50 mg/dl.

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Apolipoprotein B (Apo-B), A5353

Apo-B levels correlate with the risk of coronary disease. Apo-B exists in human plasma in two isoforms, Apo-B48 and Apo-B100. Apo-B100 is the major physiological ligand for the LDL receptor. Apo-B100 is a large monomeric protein, containing 4536 amino acids (MW 515,000). Apo-B100 is synthesized in the liver and is required for the assembly of VLDL. It does not interchange between lipoprotein particles, as do the other apolipoproteins, and it is found in IDL and LDL after the removal of the Apo-A, E and C. Apo-B48 is present in chylomicrons and their remnants. It is essential for the intestinal absorption of dietary lipids.

Apo-B48 is synthesized in the small intestine. It comprises approximately half of the N-terminal region of Apo-B100 and is the result of posttranscriptional mRNA editing by a stop codon in the intestine not found in the liver. The concentration of Apo-B in normal plasma is ~90 mg/dl.

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Apolipoprotein CI (Apo-CI), A7785

Apo-CI has been found to activate LCAT. The normal plasma concentration of Apo-CI is 4-7 mg/dl and the MW is 6,600.

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Apolipoprotein CII (Apo-CII), A7910

Apo-CII activates lipoprotein lipase. The normal plasma concentration of Apo-CII is 3-8 mg/dl. The MW is MW 8,800. Lipoprotein Lipase hydrolyzes fatty acids from triacylglycerols in chylomicrons.

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Apolipoprotein CIII (Apo-CIII)

The normal plasma concentration of Apo-CIII is 8-15 mg/dl. The MW is 8,750. The physiological role of Apo-CIII is unclear. It may inhibit the activation of lipoprotein lipase by Apo-CII.

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Apolipoprotein D (Apo-D)

Apo-D is a 29-kDa glycoprotein primarily associated with HDL. Apo-D has been found to bind cholesterol, progesterone, pregnenolone, bilirubin and arachidonic acid. However it has not been confirmed which of these may be natural ligands. Accumulation of Apo-D may be associated with increased risk of breast cancer and Alzheimer's disease.

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Apolipoprotein E (Apo-E)

Apo-E is a 34-37 kDa glycosylated protein. Concentration in normal plasma is 5 mg/dl. Apo-E is involved with triglyceride, phospholipid, cholesteryl ester, and cholesterol transport in and out of cells and is a ligand for LDL receptors. Apo-E has also been implicated in immune and nerve degeneration. It has been found to suppress lymphocyte proliferation. Late-onset familial and sporadic Alzheimer disease patients have been found to have a higher occurrence of one of the three common Apo-E isoforms, Apo-E4. The Apo-E4 isoform has been detected in senile plaques and neurofibrillary tangles of Alzheimer disease patients. Apo-E4 is associated with rapid chylomicron-remnant clearance and increased total cholesterol levels.

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References

 

  1. Delahunty, T., et al., "The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). I. The amino acid sequence of cyanogen bromide fragment II". J. Biol. Chem., 250, 2718-2724 (1975).
  2. Kostner, G., and Alaupovic, "Studies of the composition and structure of plasma lipoproteins. C- and N-terminal amino acids of the two nonidentical polypeptides of human plasma apolipoprotein A". FEBS Letters, 15, 320-324 (1971).
  3. Menzel, H.J., and Assmann, G. "Human apolipoprotein A-I polymorphism. Identification of amino acid substitutions in three electrophoretic variants of the Munster-3 type". J. Biol. Chem., 259, 3070-3076 (1984).
  4. Stone, W.L., and Reynolds, J.A.., J. Biol. Chem., 250, 8045-8048 (1975).
  5. Kane, J.P. "Apolipoprotein B: structural and metabolic heterogeneity". Annu. Rev. Physiol., 45, 637-650 (1983).
  6. Fielding, C.J., et al. "A protein cofactor of lecithin:cholesterol acyltransferase". Biochem. Biophys. Res. Comm., 46, 1493-1498 (1972).
  7. Frank, P.G, and Marcel, Y.L., "Apolipoprotein A-I: structure-function relationships". J. Lipid Res., 41, 853-72 (2000).
  8. Chen, S.H., et al. "The complete cDNA and amino acid sequence of human apolipoprotein B-100". J. Biol. Chem., 261, 12918-12921 (1986).
  9. Law, S.W., et al. "Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence". Proc. Natl. Acad. Sci. USA, 83, 8142-8146 (1986).
  10. Young, S.G. "Recent progress in understanding apolipoprotein B". Circulation, 82, 1574-1594 (1990).
  11. Chen, S.H., et al. "Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon". Science, 238, 363-366 (1987).
  12. Jonas, A., et. Al. "Discoidal complexes of A and C apolipoproteins with lipids and their reactions with lecithin: cholesterol acyltransferase". J. Biol. Chem., 259, 6369-6375 (1984).
  13. Steyrer, E., and Kostner, G. M. "Activation of lecithin-cholesterol acyltransferase by apolipoprotein D: comparison of proteoliposomes containing apolipoprotein D, A-I or C-I". Biochim. Biophys. Acta, 958, 484-491 (1988).
  14. Rassart, E., et al. "Apolipoprotein D". Biochim. Biophys. Acta, 1482, 185-98 (2000).
  15. Pepe, M. G., Curtiss, L. K.. "Apolipoprotein E is a biologically active constituent of the normal immunoregulatory lipoprotein LDL". J. Immunol., 136, 3716-3723 (1986).
  16. Corder, E.H. et al. "Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families". Science, 261, 921 (1993).
  17. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Strittmatter, W.J., et al. 1993. Proc. Natl. Acad. Sci. USA, 90.
  18. Barclay, M., Lipoprotein Class Distribution in Normal and Disease State, Wiley-Interscience: New York, New York, p.585 (1972).

 

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