Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans

• Published in: Journal of lipid research Vol. 36; no. 7; pp. 1618 - 1628
• Main Authors: Fisher, W R, Venkatakrishnan, V, Zech, L A, Hall, C M, Kilgore, L L, Stacpoole, P W, Diffenderfer, M R, Friday, K E, Sumner, A E, Marsh, J B
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.07.1995
• Subjects: Apolipoprotein A-I - biosynthesis; Apolipoprotein A-I - metabolism; Apolipoprotein A-II - biosynthesis; Apolipoprotein A-II - metabolism; Female; Humans; Hyperlipoproteinemia Type II - blood; Kinetics; Leucine - metabolism; Middle Aged; Tritium
• DOI: 10.1016/S0022-2275(20)39747-9
• ISSN: 0022-2275

The kinetics of apolipoproteins A-I and A-II were examined in human subjects using leucine tracers administered intravenously. High density lipoproteins were separated and apoA-I and A-II were isolated. The specific activity or enrichment data for these apolipoprotein were analyzed by mathematical compartmental modeling. In 11 of 14 subjects studied with a bolus-injected [3H]leucine tracer, in 3 subjects studied similarly with [3H]leucine, and in one subject studied by primed dose, constant infusion of [3H]leucine, a rapidly turning-over apoA-I fraction was resolved. A similar component was observed in 7 of 10 studies of apoA-II. The apoA-I data were analyzed using a compartmental model (Zech, L.A. et al. 1983. J. Lipid Res. 24: 60-71) modified to incorporate plasma leucine as a precursor for apoprotein synthesis. The data permitted resolution of two apoA-I pools, one, C(2), turned-over with a residence time of less than 1 day, the other, C(1), a slowly turning-over pool, appeared in plasma after a delay of less than half a day. C(1) comprised the predominant mass of apoA-I and was also the primary determinant of the residence time of apoA-I. Although the mass of the fast pool, C(2), was considerably less than that of C(1), because of its rapid turnover, the quantities of apoA-I transported through this fast pathway were 2- to 4-fold greater. These kinetic studies indicate that apoA-I is secreted into both fast and slowly turning-over plasma pools. The latter is predominantly measured with radioiodinated apoA-I tracers. The data can be analyzed by postulating either separate input pathways to each of the pools or by assuming the fast pool is the precursor to the slow pool. Thus, apoA-I could be initially secreted as a family of particles that are rapidly cleared from plasma, and a portion of this apoprotein then reappears in a slowly turning-over pool that constitutes the major mass of apoA-I. The physiologic identity of these kinetically distinct apoA-I species is unknown; however, the fast pool of apoA-I demonstrated in these studies is strikingly similar to that seen in subjects with Tangier disease who lack the slow pool.