In vivo metabolism of a mutant apolipoprotein, apoA-I(Iowa), associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis

D. J. Rader, R. E. Gregg, M. S. Meng, J. R. Schaefer, L. A. Zech, M. D. Benson, H. B. Brewer

Research output: Contribution to journalArticle

76 Scopus citations


Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). A kindred has been identified in which a glycine to arginine mutation at residue 26 in apoA-I is associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. We isolated the mutant protein, termed apoA-I(Iowa), from the plasma of an affected subject and studied its in vivo metabolism compared to that of normal apoA-I in two heterozygous apoA-I(Iowa) subjects and two normal controls. Normal and mutant apoA-I were radioiodinated with 131I and 125I, respectively, reassociated with autologous plasma lipoproteins, and simultaneously injected into all subjects. Kinetic analysis of the plasma radioactivity curves demonstrated that the mutant apoA-I(Iowa) was rapidly cleared from plasma (mean fractional catabolic rate [FCR] 0.559 day-1) compared with normal apoA-I (mean FCR 0.244 day-1) in all four subjects. The FCR of normal apoA- I was also substantially faster in the heterozygous apoA-I(Iowa) subjects (mean FCR 0.281 days-1) than in the normal controls (mean FCR 0.203 days- 1). Despite the rapid removal from plasma of apoA-I(Iowa), the cumulative urinary excretion of its associated radioactivity after 2 weeks (44%) of the injected dose) was substantially less than that associated with normal apoA-I (78% of injected dose), indicating extravascular sequestration of radiolabeled apoA-I(Iowa). Therefore, the single amino acid substitution in apoA-I(Iowa) results in both rapid clearance of apoA-I, explaining the low levels of plasma HDL and apoA-I, as well as extravascular sequestration of the mutant apolipoprotein, consistent with the formation of amyloid deposits containing aggregates of apoA-I(Iowa), in heterozygous carriers of this unique apoA-I variant.

Original languageEnglish (US)
Pages (from-to)755-763
Number of pages9
JournalJournal of Lipid Research
Issue number5
StatePublished - Jan 1 1992
Externally publishedYes


  • apoA-I kinetics
  • high density lipoproteins
  • kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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