Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans
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 c...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1995-07-01
|
| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520397479 |
| _version_ | 1818647387963392000 |
|---|---|
| author | W R Fisher V Venkatakrishnan L A Zech C M Hall L L Kilgore P W Stacpoole M R Diffenderfer K E Friday A E Sumner J B Marsh |
| author_facet | W R Fisher V Venkatakrishnan L A Zech C M Hall L L Kilgore P W Stacpoole M R Diffenderfer K E Friday A E Sumner J B Marsh |
| author_sort | W R Fisher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:01:44Z |
| format | Article |
| id | doaj.art-9b46670b53a249ddb0b67d9d1efa0eea |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T01:01:44Z |
| publishDate | 1995-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-9b46670b53a249ddb0b67d9d1efa0eea2022-12-21T22:09:25ZengElsevierJournal of Lipid Research0022-22751995-07-0136716181628Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humansW R Fisher0V Venkatakrishnan1L A Zech2C M Hall3L L Kilgore4P W Stacpoole5M R Diffenderfer6K E Friday7A E Sumner8J B Marsh9Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.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.http://www.sciencedirect.com/science/article/pii/S0022227520397479 |
| spellingShingle | W R Fisher V Venkatakrishnan L A Zech C M Hall L L Kilgore P W Stacpoole M R Diffenderfer K E Friday A E Sumner J B Marsh Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans Journal of Lipid Research |
| title | Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans |
| title_full | Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans |
| title_fullStr | Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans |
| title_full_unstemmed | Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans |
| title_short | Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans |
| title_sort | kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein a i in humans |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520397479 |
| work_keys_str_mv | AT wrfisher kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT vvenkatakrishnan kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT lazech kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT cmhall kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT llkilgore kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT pwstacpoole kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT mrdiffenderfer kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT kefriday kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT aesumner kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans AT jbmarsh kineticevidenceforbothafastandaslowsecretorypathwayforapolipoproteinaiinhumans |