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. 1985 Feb;82(3):874–878. doi: 10.1073/pnas.82.3.874

Proapolipoprotein A-I conversion kinetics in vivo in human and in rat.

G Ghiselli, A M Gotto Jr, S Tanenbaum, B C Sherrill
PMCID: PMC397149  PMID: 3919384

Abstract

We have determined the turnover rates for proapolipoprotein A-I (proapoA-I) and mature apolipoprotein A-I (apoA-I) in vivo in human and in rat. For the human study, high density lipoprotein (HDL)-associated 125I-labeled proapoA-I (A-I isoform 1) and 131I-labeled mature apoA-I (A-I isoforms 3, 4, and 5) were injected simultaneously into two normal volunteers. Blood samples were obtained serially and HDL proapoA-I and mature apoA-I were separated by isoelectrofocusing for the determination of the associated radioactivity. Residence times of proapoA-I and mature apoA-I were 0.13 and 3.9 days and production rates were 9.0 and 9.3 mg/kg per day, respectively. Analysis of the specific activity curves suggested a complete proapoA-I to mature apoA-I precursor-product relationship. Proprotein conversion was virtually completed in 24 hr. For the rat study, HDL- and lymph chylomicron- (flotation constant Sf greater than 400 S) associated 125I-labeled proapoA-I and 131I-mature apoA-I were injected into fasted rats. Residence times of proapoA-I and mature apoA-I injected in association with HDL were 0.13 and 0.28 day, respectively, and for injection associated with chylomicrons the residence times were 0.08 and 0.26 day. When associated with chylomicrons, proapoA-I was converted more efficiently to the mature form. As in the human study, the results demonstrated a complete proapoA-I to mature apoA-I precursor-product relationship. Our data are consistent with the concepts that (i) conversion to mature apoA-I is the major proapoA-I catabolic fate in plasma; (ii) mature apoA-I is conceivably derived solely from proapoA-I in plasma and proapoA-I is the major apoA-I form secreted in vivo; and (iii) a putative proapoA-I-chylomicron complex is the preferred substrate for the apoA-I propeptidase.

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Selected References

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  1. Cheung M. C., Albers J. J. The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay. J Clin Invest. 1977 Jul;60(1):43–50. doi: 10.1172/JCI108767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cheung P., Chan L. Nucleotide sequence of cloned cDNA of human apolipoprotein A-I. Nucleic Acids Res. 1983 Jun 11;11(11):3703–3715. doi: 10.1093/nar/11.11.3703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Fenner C., Traut R. R., Mason D. T., Wikman-Coffelt J. Quantification of Coomassie Blue stained proteins in polyacrylamide gels based on analyses of eluted dye. Anal Biochem. 1975 Feb;63(2):595–602. doi: 10.1016/0003-2697(75)90386-3. [DOI] [PubMed] [Google Scholar]
  5. Ghiselli G., Bradley W. A., Gotto A. M., Jr, Sherrill B. C. Identification of proapoa-I in rat lymph and plasma: metabolic conversion to "mature" apoA-I. Biochem Biophys Res Commun. 1983 Oct 31;116(2):704–711. doi: 10.1016/0006-291x(83)90582-x. [DOI] [PubMed] [Google Scholar]
  6. Ghiselli G., Schaefer E. J., Light J. A., Brewer H. B., Jr Apolipoprotein A-I isoforms in human lymph: effect of fat absorption. J Lipid Res. 1983 Jun;24(6):731–736. [PubMed] [Google Scholar]
  7. 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]
  8. Jackson R. L., Morrisett J. D., Gotto A. M., Jr Lipoprotein structure and metabolism. Physiol Rev. 1976 Apr;56(2):259–316. doi: 10.1152/physrev.1976.56.2.259. [DOI] [PubMed] [Google Scholar]
  9. Law S. W., Gray G., Brewer H. B., Jr cDNA cloning of human apoA-I: amino acid sequence of preproapoA-I. Biochem Biophys Res Commun. 1983 Apr 15;112(1):257–264. doi: 10.1016/0006-291x(83)91824-7. [DOI] [PubMed] [Google Scholar]
  10. Mao S. J., Miller J. P., Gotto A. M., Jr, Sparrow J. T. The antigenic structure of apolipoprotein A-I in human high density lipoproteins. Radioimmunoassay using surface-specific antibodies. J Biol Chem. 1980 Apr 25;255(8):3448–3453. [PubMed] [Google Scholar]
  11. Miller J. C., Barth R. K., Shaw P. H., Elliott R. W., Hastie N. D. Identification of a cDNA clone for mouse apoprotein A-1 (apo A-1) and its use in characterization of apo A-1 mRNA expression in liver and small intestine. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1511–1515. doi: 10.1073/pnas.80.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Sherrill B. C., Dietschy J. M. Characterization of the sinusoidal transport process responsible for uptake of chylomicrons by the liver. J Biol Chem. 1978 Mar 25;253(6):1859–1867. [PubMed] [Google Scholar]
  14. Stoffel W., Krüger E., Deutzmann R. Cell-free translation of human liver apolipoprotein AI and AII mRNA. Processing of primary translation products. Hoppe Seylers Z Physiol Chem. 1983 Mar;364(3):227–237. doi: 10.1515/bchm2.1983.364.1.227. [DOI] [PubMed] [Google Scholar]
  15. Wu A. L., Windmueller H. G. Relative contributions by liver and intestine to individual plasma apolipoproteins in the rat. J Biol Chem. 1979 Aug 10;254(15):7316–7322. [PubMed] [Google Scholar]
  16. Zannis V. I., Breslow J. L., Katz A. J. Isoproteins of human apolipoprotein A-I demonstrated in plasma and intestinal organ culture. J Biol Chem. 1980 Sep 25;255(18):8612–8617. [PubMed] [Google Scholar]
  17. Zannis V. I., Breslow J. L., SanGiacomo T. R., Aden D. P., Knowles B. B. Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. Biochemistry. 1981 Dec 8;20(25):7089–7096. doi: 10.1021/bi00528a006. [DOI] [PubMed] [Google Scholar]
  18. Zannis V. I., Karathanasis S. K., Keutmann H. T., Goldberger G., Breslow J. L. Intracellular and extracellular processing of human apolipoprotein A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide. Proc Natl Acad Sci U S A. 1983 May;80(9):2574–2578. doi: 10.1073/pnas.80.9.2574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zannis V. I., Kurnit D. M., Breslow J. L. Hepatic apo-A-I and apo-E and intestinal apo-A-I are synthesized in precursor isoprotein forms by organ cultures of human fetal tissues. J Biol Chem. 1982 Jan 10;257(1):536–544. [PubMed] [Google Scholar]

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