| Origin of apolipoprotein A-I polymorphism in plasma. | |
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MedLine Citation:
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PMID: 4066689 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The origin and the functional significance of apo-A-I polymorphism in man has been investigated. Together with proapo-A-I (identified as A-I1 of the polymorphic series), four other isoforms are found in human plasma, namely A-I2, A-I3, A-I4, and A-I5. A-I3 is the "mature" product of proapo-A-I conversion in plasma. In this study we provide evidence that the other, more acidic, mature apo-A-I isoproteins are derived from A-I3 by a stepwise deamidation process. This conclusion is based on the following observations. 1) Incubation of A-I3 or A-I4, either free or associated with high density lipoprotein, produces a series of more acidic isoproteins corresponding to the sequence found in plasma. The conversion process fits in well with a first order reaction, and A-I3 to A-I4 conversion occurs virtually at the same rate as A-I4 to A-I5 conversion. 2) A-I3 and A-I4 have the same NH2- and C-terminal residues. 3) Formation of apo-A-I acidic isoproteins is accompanied by liberation of ammonia. In order to investigate whether deamidation of apo-A-I results in the production of forms which have different catabolism, a series of turnover studies was carried out in normal volunteers. A-I3 and A-I4 residence times in plasma were, respectively, 3.50 +/- 0.16 and 3.00 +/- 0.10 days (mean +/- S.E.; n = 3). Degradation rate of A-I3 was 8.81 +/- 0.69 mg/kg/day and that of A-I4 was 1.66 +/- 0.15 mg/kg/day (mean +/- S.E.; n = 3). Conversion of A-I3 to A-I4 and A-I4 to A-I5 occurred at the same rate in vivo as that observed in vitro. These results are consistent with the concept that A-I3 is the precursor to the other mature apo-A-I isoforms in plasma. A-I3 is the major isoform through which apo-A-I is eliminated from plasma. |
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Authors:
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G Ghiselli; M F Rohde; S Tanenbaum; S Krishnan; A M Gotto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 260 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1985 Dec |
Date Detail:
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Created Date: 1986-01-16 Completed Date: 1986-01-16 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 15662-8 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Ammonia
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metabolism Apolipoprotein A-I Apolipoproteins A / blood* Humans Hydrogen-Ion Concentration Kinetics Lipoproteins, HDL / blood Mathematics Protein Precursors / blood* Temperature |
| Grant Support | |
ID/Acronym/Agency:
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HL 27431/HL/NHLBI NIH HHS; RR-05425/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein A-I; 0/Apolipoproteins A; 0/Lipoproteins, HDL; 0/Protein Precursors; 7664-41-7/Ammonia |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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