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In vivo metabolism of proapolipoprotein A-I in Tangier disease.

Abstract
Tangier disease is a rare familial disorder characterized by extremely low levels of apolipoprotein A-I (apoA-I) and high density lipoproteins (HDL). In normal subjects, proapoA-I is secreted into plasma and converted to mature apoA-I by the cleavage of the amino-terminal six amino acids with the major isoprotein in plasma being mature apoA-I. In contrast, in Tangier disease there is a marked relative increase of proapoA-I as compared with mature apoA-I. ProapoA-I and mature apoA-I were isolated from normal and Tangier disease subjects, radio-labeled, and autologous apoA-I isoproteins injected into normal and Tangier subjects. The in vivo catabolism and conversion of proapoA-I and mature apoA-I in normal and Tangier disease subjects were quantitated. A comparison of the rate of catabolism of apoA-I isoproteins from plasma revealed a significantly faster rate of catabolism of both isoproteins of apoA-I in Tangier subjects when compared with normal subjects. The fractional conversion rate of proapoA-I to mature apoA-I was 3.9 d-1 in normal subjects and 3.6 d-1 in Tangier subjects. The results indicate that (a) apoA-I enters plasma as the pro isoprotein in both normal and Tangier subjects, (b) Tangier disease subjects have a normal fractional rate of conversion of proapoA-I to mature apoA-I, (c) proapoA-I is catabolized at the same rate as mature apoA-I in Tangier subjects, and (d) Tangier subjects catabolize both pro and mature apoA-I at a much greater rate than do normal subjects. Therefore, the relative increase in proapoA-I in Tangier disease is due to a marked decrease in mature apoA-I resulting from rapid catabolism of both pro- and mature apoA-I and not to defective conversion of proapoA-I to mature apoA-I.
AuthorsD Bojanovski, R E Gregg, L A Zech, M S Meng, C Bishop, R Ronan, H B Brewer Jr
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 80 Issue 6 Pg. 1742-7 (Dec 1987) ISSN: 0021-9738 [Print] United States
PMID3119665 (Publication Type: Journal Article)
Chemical References
  • Apolipoprotein A-I
  • Apolipoproteins A
  • Protein Precursors
Topics
  • Adult
  • Apolipoprotein A-I
  • Apolipoproteins A (metabolism)
  • Female
  • Humans
  • Hypolipoproteinemias (metabolism)
  • Kinetics
  • Male
  • Middle Aged
  • Protein Precursors (metabolism)
  • Tangier Disease (metabolism)

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