Origin of apolipoprotein A-I polymorphism in plasma

G. Ghiselli, M. F. Rohde, S. Tanenbaum, S. Krishnan, A. M. Gotto

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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. 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. A-I3 and A-I4 have the same NH2- and C-terminal residues. 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 occured 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 eliminated from plasma.

Original languageEnglish (US)
Pages (from-to)15662-15668
Number of pages7
JournalJournal of Biological Chemistry
Volume260
Issue number29
StatePublished - 1985

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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