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Journal of Lipid Research, Vol 32, 1849-1859, Copyright © 1991 by Lipid Research, Inc.
In vivo metabolism of apolipoprotein A-I on high density lipoprotein particles LpA-I and LpA-I,A-II
DJ Rader, G Castro, LA Zech, JC Fruchart and HB Brewer Jr
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Apolipoprotein (apo) A-I is the major protein in high density lipoproteins
(HDL) and is found in two major subclasses of lipoproteins, those
containing apolipoprotein A-II (termed LpA-I,A-II) and those without
apoA-II (termed LpA-I). The in vivo kinetics of apoA- I on LpA-I and
LpA-I,A-II were investigated in normolipidemic human subjects. In the first
series of studies, radiolabeled apoA-I and apoA- II were reassociated with
autologous plasma lipoproteins and injected into normal subjects. LpA-I and
LpA-I,A-II were isolated from plasma at selected time points by
immunoaffinity chromatography. By 24 h after injection, only 52.8 +/- 1.0%
of the apoA-I in LpA-I remained, whereas 66.9 +/- 2.7% of apoA-I in
LpA-I,A-II remained (P less than 0.01). In the second series of studies,
purified apoA-I was labeled with either 131I or 125I and reassociated with
autologous plasma. Isolated LpA-I and LpA-I,A-II particles differentially
labeled with 131I-labeled apoA- I and 125I-labeled apoA-I, respectively,
were simultaneously injected into study subjects. The plasma residence time
of apoA-I injected on LpA-I (mean 4.39 days) was substantially shorter than
that of apoA-I injected on LpA-I,A-II (mean 5.17 days), with a mean
difference in residence times of 0.79 +/- 0.08 days (P less than 0.001).
These data demonstrate that apoA-I injected on LpA-I is catabolized more
rapidly than apoA-I injected on LpA-I,A-II. The results are consistent with
the concept that LpA-I and LpA-I,A-II have divergent metabolic pathways.

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W. S. Davidson, K. L. Gillotte, S. Lund-Katz, W. J. Johnson, G. H. Rothblat, and M. C. Phillips
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M. C. de Beer, D. M. Durbin, L. Cai, N. Mirocha, A. Jonas, N. R. Webb, F. C. de Beer, and D. R. van der Westhuyzen
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Copyright © 1991 by the American Society for Biochemistry and Molecular Biology.
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