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Genomic Structure, Biosynthesis, and Processing of Preproapolipoprotein C-II

  • S. S. Fojo
  • L. Taam
  • S. W. Law
  • R. Ronan
  • C. Bishop
  • M. Meng
  • D. L. Sprecher
  • J. M. Hoeg
  • H. B. Brewer
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Apolipoprotein C-II plays a major role in lipid metabolism as a cofactor for lipoprotein lipase, the enzyme involved in the hydrolysis of plasma triglycerides. Patients with deficiency of apo C-II have marked elevations of plasma triglyceride-rich lipoproteins and are at increased risk of pancreatitis. Apolipoprotein C-II has been cloned, and the complete genomic structure elucidated. The apo C-II gene consists of four exons interrupted by three introns and encodes a 22-amino-acid signal peptide that undergoes cotranslational cleavage. The posttranslational processing of apo C-II was analyzed by two-dimensional gel electrophoresis followed by immunoblotting of apo C-II isoforms in the media of Hep G2 cells and in plasma. Four major isoforms have been identified and designated apo C-II-2, apo C-II-1, apo C-II-1/2, and apo C-II0. Neuroaminidase studies have shown that apo C-II-2 and apo C-II-1 are sialic-acid-containing glycoproteins. There is a relative enrichment of these two isoforms of apo C-II in Hep G2 cell media, but they represent minor apo C-II isoforms in normal fasting plasma. Apolipoprotein C-II0, the major plasma isoform of apo C-II, is a proprotein that undergoes proteolytic cleavage of the amino-terminal hexapeptide to form mature apo C-II (apo C-II-1/2)-Amino acid composition and amino-terminal analysis of apo C-II-1/2 confirms the loss of the six terminal amino acids of apo C-II0. In summary: (1) apo C-II has been cloned, and its complete genomic sequence determined; (2) apo C-II is synthesized as preproapo C-II, which undergoes cleavage of a 22-amino-acid signal peptide to form proapo C-II; (3) proapo C-II is glycosylated to generate the sialic-acid-containing glycoproteins apo C-II-2 and apo C-II-1; (4) apo C-II-2 and apo C-II-1 are deglycosylated to form apo C-II0; (5) apo C-II0, the major plasma isoform of apo C-II, is a proprotein; (6) proteolytic processing of apo C-IIo results in the loss of six amino terminal residues to form apo C-II-1/2, the mature apo C-II isoform. A better understanding of the structural relationship of the various plasma isoforms of apo C-II will help to elucidate the mechanisms involved in normal as well as defective processing of apo C-II.

Keywords

Lipoprotein Lipase Human Apolipoprotein Primer Extension Product Dideoxynucleotide Chain Termination Method Amino Terminal Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • S. S. Fojo
    • 1
  • L. Taam
    • 1
  • S. W. Law
    • 2
  • R. Ronan
    • 1
  • C. Bishop
    • 1
  • M. Meng
    • 1
  • D. L. Sprecher
    • 1
  • J. M. Hoeg
    • 1
  • H. B. Brewer
    • 1
  1. 1.The Molecular Disease Branch, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA

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