Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Dec;80(6):1742–1747. doi: 10.1172/JCI113266

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

D Bojanovski 1, R E Gregg 1, L A Zech 1, M S Meng 1, C Bishop 1, R Ronan 1, H B Brewer Jr 1
PMCID: PMC442448  PMID: 3119665

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.

Full text

PDF
1743

Images in this article

1744Image
on p.1744

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. W., Schaefer E. J., Bronzert T. J., Lindgren F. T., Forte T., Starzl T. E., Niblack G. D., Zech L. A., Brewer H. B., Jr Transport of apolipoproteins A-I and A-II by human thoracic duct lymph. J Clin Invest. 1981 Mar;67(3):857–866. doi: 10.1172/JCI110103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bojanovski D., Gregg R. E., Brewer H. B., Jr Tangier disease. In vitro conversion of proapo-A-ITangier to mature APO-A-ITangier. J Biol Chem. 1984 May 25;259(10):6049–6051. [PubMed] [Google Scholar]
  3. Bojanovski D., Gregg R. E., Ghiselli G., Schaefer E. J., Light J. A., Brewer H. B., Jr Human apolipoprotein A-I isoprotein metabolism: proapoA-I conversion to mature apoA-I. J Lipid Res. 1985 Feb;26(2):185–193. [PubMed] [Google Scholar]
  4. Brewer H. B., Jr, Fairwell T., Kay L., Meng M., Ronan R., Law S., Light J. A. Human plasma proapoA-I: isolation and amino-terminal sequence. Biochem Biophys Res Commun. 1983 Jun 15;113(2):626–632. doi: 10.1016/0006-291x(83)91772-2. [DOI] [PubMed] [Google Scholar]
  5. Brewer H. B., Jr, Fairwell T., LaRue A., Ronan R., Houser A., Bronzert T. J. The amino acid sequence of human APOA-I, an apolipoprotein isolated from high density lipoproteins. Biochem Biophys Res Commun. 1978 Feb 14;80(3):623–630. doi: 10.1016/0006-291x(78)91614-5. [DOI] [PubMed] [Google Scholar]
  6. Brewer H. B., Jr, Fairwell T., Meng M., Kay L., Ronan R. Human proapoA-ITangier: isolation of proapoA-ITangier and amino acid sequence of the propeptide. Biochem Biophys Res Commun. 1983 Jun 29;113(3):934–940. doi: 10.1016/0006-291x(83)91088-4. [DOI] [PubMed] [Google Scholar]
  7. Brewer H. B., Jr, Ronan R., Meng M., Bishop C. Isolation and characterization of apolipoproteins A-I, A-II, and A-IV. Methods Enzymol. 1986;128:223–246. doi: 10.1016/0076-6879(86)28070-2. [DOI] [PubMed] [Google Scholar]
  8. Edelstein C., Gordon J. I., Toscas K., Sims H. F., Strauss A. W., Scanu A. M. In vitro conversion of proapoprotein A-I to apoprotein A-I. Partial characterization of an extracellular enzyme activity. J Biol Chem. 1983 Oct 10;258(19):11430–11433. [PubMed] [Google Scholar]
  9. Edelstein C., Gordon J. I., Vergani C. A., Catapano A. L., Pietrini V., Scanu A. M. Comparative in vitro study of the pro-apolipoprotein A-I to apolipoprotein A-I converting activity between normal and Tangier plasma. J Clin Invest. 1984 Sep;74(3):1098–1103. doi: 10.1172/JCI111477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gordon J. I., Sims H. F., Lentz S. R., Edelstein C., Scanu A. M., Strauss A. W. Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease. J Biol Chem. 1983 Mar 25;258(6):4037–4044. [PubMed] [Google Scholar]
  11. Gregg R. E., Zech L. A., Schaefer E. J., Brewer H. B., Jr Apolipoprotein E metabolism in normolipoproteinemic human subjects. J Lipid Res. 1984 Nov;25(11):1167–1176. [PubMed] [Google Scholar]
  12. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Law S. W., Brewer H. B., Jr Tangier disease. The complete mRNA sequence encoding for preproapo-A-I. J Biol Chem. 1985 Oct 15;260(23):12810–12814. [PubMed] [Google Scholar]
  15. Schaefer E. J., Blum C. B., Levy R. I., Jenkins L. L., Alaupovic P., Foster D. M., Brewer H. B., Jr Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. N Engl J Med. 1978 Oct 26;299(17):905–910. doi: 10.1056/NEJM197810262991701. [DOI] [PubMed] [Google Scholar]
  16. Schaefer E. J., Kay L. L., Zech L. A., Brewer H. B., Jr Tangier disease. High density lipoprotein deficiency due to defective metabolism of an abnormal apolipoprotein A-i (ApoA-ITangier). J Clin Invest. 1982 Nov;70(5):934–945. doi: 10.1172/JCI110705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schaefer E. J., Zech L. A., Jenkins L. L., Bronzert T. J., Rubalcaba E. A., Lindgren F. T., Aamodt R. L., Brewer H. B., Jr Human apolipoprotein A-I and A-II metabolism. J Lipid Res. 1982 Aug;23(6):850–862. [PubMed] [Google Scholar]
  18. Schaefer E. J., Zech L. A., Schwartz D. E., Brewer H. B., Jr Coronary heart disease prevalence and other clinical features in familial high-density lipoprotein deficiency (Tangier disease). Ann Intern Med. 1980 Aug;93(2):261–266. doi: 10.7326/0003-4819-93-2-261. [DOI] [PubMed] [Google Scholar]
  19. Schmitz G., Assmann G., Rall S. C., Jr, Mahley R. W. Tangier disease: defective recombination of a specific Tangier apolipoprotein A-I isoform (pro-apo A-i) with high density lipoproteins. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6081–6085. doi: 10.1073/pnas.80.19.6081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schmitz G., Assmann G., Robenek H., Brennhausen B. Tangier disease: a disorder of intracellular membrane traffic. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6305–6309. doi: 10.1073/pnas.82.18.6305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sprecher D. L., Taam L., Brewer H. B., Jr Two-dimensional electrophoresis of human plasma apolipoproteins. Clin Chem. 1984 Dec;30(12 Pt 1):2084–2092. [PubMed] [Google Scholar]
  22. Zannis V. I., Lees A. M., Lees R. S., Breslow J. L. Abnormal apoprotein A-I isoprotein composition in patients with Tangier disease. J Biol Chem. 1982 May 10;257(9):4978–4986. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES