Lipoprotein

DATA No : TLP4601 INFORMANT : Kazuo Kondo

NAME : apolipoprotein E

COMMON NAME	:
SYMBOL	:	apo E
FORMULA	:	MOL.WT (average) :

BIOLOGICAL ACTIVITY

Function
(1) Apo E transits among lipoproteins, thus being involved in regulation of lipoprotein metabolism. (2) Apo E is involved in lipoprotein uptake via cell receptors as well as in the catabolism of lipids and proteins.(Ref. 4604)

PHYSICAL AND CHEMICAL PROPERTIES

MELTING POINT	:	Molecular weight:3,3000-3,9000 Isoelectric point:5,7-6.0(Ref. 4601)

BOILING POINT	:	The number of amino acid residues :299

REFRACTIVE INDEX	:	Amino acid sequences:Further investigations are required.

OPTICAL ROTATION	:	Structure:Arginine accounts for a relatively large proportion of structural amino acids (10 - 12 mol%). When the secondary structure of apo E is examined, 62% of structural amino acids form 11 a-helix segment, 11% of structural amino acids form 8 b-turns, 9% of structural amino acids form 3 short sheets, and the remaining amino acids form random coils which are mainly located at the region between the 164th and 202nd amino acid residues.

DENSITY	:	Amino acid compositions (Ref. 4611)

SOLUBILITY	:	Properties:The size and electric charge of apo E vary.(Ref. 4602/4603)

SPECTRAL DATA

UV SPECTRA	:

IR SPECTRA	:

NMR SPECTRA	:

MASS SPECTRA	:

OTHER SPECTRA	:

CHROMATOGRAM DATA

Method of purification
Lipoproteins are initially separated by ultracentrifugation. After defatting, apoproteins are separated and purified by column chromatography.

SOURCE

Existing condition and distribution of lipoprotein
In blood, apo E is bound to lipids, and accounts for 15% of apoproteins in VLDL. A small amount of apo E is also contained in chylomicron, chylomicron remnant, HDL, and LDL.

CHEMICAL SYNTHESIS

Sites of synthesis:The liver
The rate of synthesis:5.2mg/kg/day

METABOLISM

Metabolism
Apo E is synthesized in the liver, and contained in VLDL and nascent HDL. When lipoprotein lipase acts on VLDL, a part of apo E in VLDL is released and transferred to HDL. When LCAT acts on HDL, apo E in HDL is transferred to VLDL. The respective lipoproteins are taken up after being bound to LDL receptors, chylomicron remnant receptors, and apo E receptors.
Half life:0.4days(Ref. 4605/4606/4607)

GENETIC INFORMATION

Genetic information
Gene locus:19;
Gene arrangement (DNA)(Ref. 4612)
Information of gene aberration:Apo E3 is a wild type of apo E. In apo E2 and E4, mutual replacement occurs between arginine and cysteine at the 112th and 158th amino acid residues of apo E3, respectively.
Information of genetic diseases :apo E2 homozygote
Phenotypes:E1,E2,E3,E4,E5,E7(Ref. 4608/4609/4610)

NOTE

Standard range:2.8- 4.6mg/dl (in human sera)
Diseases and drugs that induce abnormal levels of apo E.
Congenital apo E abnormalities (dyslipoproteinemia caused by apo E2 homozygote, apo E deficiency, b-lipoprotein abnormalities demonstrating E3/3) and risk factors for Alzheimer's disease (apo E4).
Analytical methods:TIA,ELISA,Nephelometry,SRID etc.

REFERENCES

[4601]

AUTHOR	:	Weisgraber, K. H., Troxler, R. F., Rall, S. C., and Mahley, R. W.
TITLE	:	Comparison of the human, canine and swine E apoproteins PubMed ID:7417263
JOURNAL	:	Biochem Biophys Res Commun.
VOL	:	95 PAGE : 374-380 (1980)

[TOP]

[4602]

AUTHOR	:	Utermann, G.
TITLE	:	Isolation and partial characterization of an arginine-rich apolipoprotein from human plasma very-low-density lipoproteins: apolipoprotein E PubMed ID:172422
JOURNAL	:	Hoppe Seylers Z Physiol Chem.
VOL	:	356 PAGE : 1113-1121 (1975)

[TOP]

[4603]

AUTHOR	:	Utermann, G., Jaeschke, M., and Menzel, J.
TITLE	:	Familial hyperlipoproteinemia type III: deficiency of a specific apolipoprotein (apo E-III) in the very-low-density lipoproteins PubMed ID:169165
JOURNAL	:	FEBS Lett.
VOL	:	56 PAGE : 352-355 (1975)

[TOP]

[4604]

AUTHOR	:	Yamada, N., and Murase, T.
TITLE	:	Modulation, by apolipoprotein E, of lipoprotein lipase activity PubMed ID:7396930
JOURNAL	:	Biochem Biophys Res Commun.
VOL	:	94 PAGE : 710-715 (1980)

[TOP]

[4605]

AUTHOR	:	Blum, C. B., Aron, L., and Sciacca, R.
TITLE	:	Radioimmunoassay studies of human apolipoprotein E PubMed ID:7440713
JOURNAL	:	J Clin Invest.
VOL	:	66 PAGE : 1240-1250 (1980)

[TOP]

[4606]

AUTHOR	:	Marsh,J.B.
TITLE	:	Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver. PubMed ID:176290
JOURNAL	:	J.Lipid Res.
VOL	:	17 PAGE : 85 -89 (1976)

[TOP]

[4607]

AUTHOR	:	Hamilton, R. L., Williams, M. C., Fielding, C. J., and Havel, R. J.
TITLE	:	Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver PubMed ID:182724
JOURNAL	:	J Clin Invest.
VOL	:	58 PAGE : 667-680 (1976)

[TOP]

[4608]

AUTHOR	:	Havel, R. J., Kotite, L., Vigne, J. L., Kane, J. P., Tun, P., Phillips, N., and Chen, G. C.
TITLE	:	Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E. Concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency PubMed ID:7440719
JOURNAL	:	J Clin Invest.
VOL	:	66 PAGE : 1351-1362 (1980)

[TOP]

[4609]

AUTHOR	:	Ghiselli, G., Schaefer, E. J., Gascon, P., and Breser, H. B., Jr.
TITLE	:	Type III hyperlipoproteinemia associated with apolipoprotein E deficiency PubMed ID:6795720
JOURNAL	:	Science.
VOL	:	214 PAGE : 1239-1241 (1981)

[TOP]

[4610]

AUTHOR	:	Havel, R. J., Kotite, L., Kane, J. P., Tun, P., and Bersot, T.
TITLE	:	Atypical familial dysbetalipoproteinemia associated with apolipoprotein phenotype E3/3 PubMed ID:6860421
JOURNAL	:	J Clin Invest.
VOL	:	72 PAGE : 379-387 (1983)

[TOP]

[4611]

AUTHOR	:	Rall,S.C.Jr., Weisgraber,K.H., and Mahley,R.W.(1986) Isolation and Characterization of Apolipoprotein E, in Methods in ENZYMOLOGY Vol.128 (Segrest J.P., and Albers J.J., eds), pp223-246, Academic Press, Inc.
TITLE	:
JOURNAL	:
VOL	:	PAGE : - ()

[TOP]

[4612]

AUTHOR	:	Breslow, J. L., McPherson, J., Nussbaum, A. L., Williams, H. W., Lofquist-Kahl, F., Karathanasis, S. K., and Zannis, V. I.
TITLE	:	Identification and DNA sequence of a human apolipoprotein E cDNA clone PubMed ID:6897404
JOURNAL	:	J Biol Chem.
VOL	:	257 PAGE : 14639-14641 (1982)

[TOP]