Document Detail


Origin of apolipoprotein A-I polymorphism in plasma.
MedLine Citation:
PMID:  4066689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
G Ghiselli; M F Rohde; S Tanenbaum; S Krishnan; A M Gotto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  260     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1985 Dec 
Date Detail:
Created Date:  1986-01-16     Completed Date:  1986-01-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15662-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Ammonia / 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:
HL 27431/HL/NHLBI NIH HHS; RR-05425/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Apolipoproteins A; 0/Lipoproteins, HDL; 0/Protein Precursors; 7664-41-7/Ammonia

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