Human preproapolipoprotein C-II. Analysis of major plasma isoforms

Area of Science:

• Biochemistry
• Lipid Metabolism
• Protein Processing

Background:

• Apolipoprotein C-II (Apo-C-II) is crucial for lipid metabolism, acting as a cofactor for lipoprotein lipase.
• Apo-C-II is synthesized as a 101 amino acid protein with signal peptide cleavage.
• Post-translational modifications of Apo-C-II have not been previously characterized.

Purpose of the Study:

• To identify and characterize the plasma isoforms of Apolipoprotein C-II.
• To elucidate the post-translational processing pathway of Apo-C-II.

Main Methods:

• Two-dimensional gel electrophoresis and immunoblot analysis to identify Apo-C-II isoforms.
• Neuraminidase treatment to assess glycosylation.
• Amino acid composition and N-terminal analysis to determine protein structure.

Main Results:

• Four major plasma isoforms of Apo-C-II were identified, resulting from post-translational modifications.
• Two isoforms were identified as sialic acid-containing glycoproteins.
• The predominant plasma isoform is proApo-C-II, which is proteolytically cleaved to mature Apo-C-II.

Conclusions:

• Apo-C-II is secreted as a glycosylated proprotein (proApo-C-II).
• ProApo-C-II undergoes deglycosylation and proteolytic cleavage to yield mature Apo-C-II.
• Understanding Apo-C-II isoform processing is key to understanding lipid metabolism defects.