Cited by 305Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

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Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112

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Weisgraber, K H·1990·Journal of Lipid Research

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Abstract

Human apolipoprotein (apo) E occurs as three common isoforms (apoE4, E3, and E2), all of which influence plasma cholesterol levels. Although both apoE4 and E3 bind with equal effectiveness to the low density lipoprotein receptor, they associate preferentially with different classes of plasma lipoproteins: apoE4 with very low density lipoproteins, apoE3 with high density lipoproteins. The primary structure of apoE3 differs from that of apoE4 at only a single site; apoE3 has its sole cysteine residue at position 112, while apoE4 contains arginine at position 112 and completely lacks cysteine. The present study investigated how this structural difference between apoE4 and E3 determines their distribution among plasma lipoproteins, and analyzed the role of the disulfide-linked heterodimer apoE-A-II (which apoE4 cannot form) in determining the distribution. Human plasma was incubated with 125I-labeled apoE, and lipoproteins were separated by agarose chromatography. Both apoE3 that had been reduced and alkylated with iodoacetamide and apoE3-A-II distributed with high density lipoproteins, indicating that a combination of an inherent property of the monomeric apoE3 structure and apoE-A-II formation account for distribution of apoE3 to the high density lipoproteins. Cysteamine modification of apoE3 resulted in an apoE4-like distribution, demonstrating that a positive charge at position 112 determined the apoE4 distribution and that the effect was not exclusively due to the presence o…

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Authors: Weisgraber, K. H.
Affiliations: University of California, San Francisco (US)
Corresponding author: Weisgraber, K H
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 1990-08
Volume: 31
Issue: 8
Pages: 1503-1511
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1016/s0022-2275(20)42621-5
OpenAlex: W2155559959
Cited by: 304
References: 26
Citations by year: 2026: 9 · 2025: 13 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 4 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 9 · 2012: 5
FWCI: 14.01
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 11035 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-41633, P01HL041633)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: apolipoprotein E, apolipoprotein E isoforms, APOE ε4, APOE3, APOE2, serum lipoproteins, high-density lipoprotein, VLDL, disulfide bonds, serum cholesterol, LDL receptor
MeSH terms: Apolipoproteins E, Arginine, Cysteine, Humans, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, Lipoproteins, IDL

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Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112

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