1991/05/01 by Arnold von Eckardstein, Harald Holz, M. Sandkamp +3 · 5 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Chemistry · #Glycosylation and Glycoproteins Research #Lipid metabolism and disorders #Diabetes, Cardiovascular Risks, and Lipoproteins #Apolipoprotein B #Chemistry #Isoelectric focusing #Biochemistry #Molecular biology #Very low-density lipoprotein #Cholesterol #Lipoprotein #Biology #Enzyme
paper · pdf · doi:10.1172/jci115190
openalex publication_date 1991/05/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
Apolipoprotein C-III is a major protein constituent of triglyceride rich lipoproteins and HDL. It occurs in plasma in three isoforms differing by their sialic acid content. Apo C-III putatively inhibits lipolysis and the apo E mediated hepatic uptake of remnants from triglyceride rich particles. We identified a heterozygous carrier of an apolipoprotein C-III variant by the presence of additional bands after isoelectric focusing (IEF) of VLDL. Structural analysis of the variant protein by HPLC, time-of-flight secondary ion mass spectrometry, and automated gas phase sequencing revealed a lysine to glutamic acid replacement in position 58. The underlying A to G exchange was verified by direct sequencing subsequent to amplification by polymerase chain reaction of exon 4 of the apo C-III gene. Family studies revealed vertical transmission of this defect. The two variant carriers exhibited plasma concentrations of HDL cholesterol and apo A-I above the 95th percentiles of sex matched controls whereas the unaffected father and sister showed normal values. The plasma concentrations of apo C-III in the two variant carriers were decreased by 30-40% compared with those of the two unaffected family members and to random controls. Using two-dimensional immunoelectrophoresis as well as IEF and subsequent scanning densitometry, we found that the low serum concentration of apo C-III was a consequence of diminished concentrations of the variant apo C-III isoproteins in both VLDL (15% of normal) and HDL (25% of normal). Apo C-III(Lys58----Glu) heterozygotes possessed unusual HDL as demonstrated by nondenaturing gradient gel electrophoresis. They consisted mainly of HDL2b and contained a proportion of atypically large particles, enriched in apo E, with a Stokes diameter of 13-18 nm and resembling HDLc. In conclusion, heterozygosity for a structural apo C-III variant--apo C-III(Lys58----Glu)--was identified in two hyperalphalipoproteinemic subjects characterized by the presence of low plasma apo C-III concentrations and atypically large HDL.