The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112
Open accessAbstract
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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In the citing paper
“The difference in lipoprotein distribution between apoE3 and apoE4 has been shown to be due to the polymorphism at position 112 (21), where the presence of an arginine directs the apoprotein more to the VLDL.”
From Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. (1993) · cites this paper as [21]
In the citing paper
“It has been demonstrated previously that the polymorphis at position 112 affects the affinity of apoE for lipoproteins, with apoE4 (arginine 112) preferring VLDL to HDL relative to apoE3, which prefers HDL to VLDL (21).”
From Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. (1993) · cites this paper as [21]
In the citing paper
“The three isoforms differ at two residues: ApoE2 carries Cys112/Cys158, ApoE3 carries Cys112/Arg158, and ApoE4 carries Arg112/Arg158.”
In the citing paper
“Early work showed that, in the blood, APOE4 preferentially associates with VLDL, whereas APOE3 displays a preference for HDL (Gregg et al., 1986;Steinmetz et al., 1989;Weisgraber, 1990).”
From Isoform- and cell-state-specific lipidation of ApoE in astrocytes (2022) · cites this paper as Weisgraber, 1990
In the citing paper
“ApoE is produced for systemic circulation throughout the body by hepatocytes in the liver where approximately 70% of ApoE is present in very low density lipoproteins (VLDL) while approximately 30% is present in HDL [13].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [13]
Citations
Cites
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981
Plasma lipoproteins: apolipoprotein structure and function.
Mahley, R. W., Innerarity, T. L., Rall, S. C., & Weisgraber, K. H. (1984) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34443-6 · Cited by 1,155
Self-citationWeisgraber, K. H., Rall, S. C., & Mahley, R. W. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52510-8 · Cited by 777
Self-citationLipoprotein receptors and cholesterol homeostasis
Mahley, R. W., & Innerarity, T. L. (1983) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(83)90001-1 · Cited by 756
Human apolipoprotein E. The complete amino acid sequence
Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34702-1 · Cited by 741
Self-citationDietary fat clearance in normal subjects is regulated by genetic variation in apolipoprotein E.
Weintraub, M. S., Eisenberg, S., & Breslow, J. L. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113243 · Cited by 418
Ehnholm, C., Lukka, M., Kuusi, T., Nikkilä, E. A., & Utermann, G. (1987) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38833-7 · Cited by 403
Abnormal in vivo metabolism of apolipoprotein E4 in humans.
Gregg, R. E., Zech, L. A., Schaefer, E. J., Stark, D., Wilson, D., & Brewer, H. B. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112645 · Cited by 345
Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains.
Wetterau, J. R., Aggerbeck, L. P., Rall, S. C., & Weisgraber, K. H. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68778-2 · Cited by 293
Self-citation
Research works printed but not linked: 1
- Gregg, 1986, Role of cysteine residues in modulating in vivo metabolism of apoE in humans, Arteriosclerosis., 6, 566a
Cited by
Sorted by citations
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363
Self-citationMahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912
Self-citationApolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830
Self-citationDifferential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795
Self-citationAssociation of apolipoprotein E genotypes with lipid levels and coronary risk
Bennet, A. M., Di Angelantonio, E., Ye, Z., Wensley, F., Dahlin, A., Ahlbom, A., Keavney, B., Collins, R., Wiman, B., de Faire, U., et al. (2007) · JAMA · doi:10.1001/jama.298.11.1300 · Cited by 794
Metadata
- 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)
- 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
- 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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