| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print April 21, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Internal Medicine, Jikei University, Tokyo, Tokyo 105-8461
Corresponding Author: kikewaki{at}jikei.ac.jp
Apolipoprotein (apo) E deficiency is a rare genetic disease characterized by palmer and tubo-eruptive xanthomas, severe type of type III hyperlipidemia, and premature atherosclerotic vascular disease. The present study was undertaken to elucidate the metabolic basis for the increased remnants and Lp(a) and decreased LDL apoB levels in human apoE deficiency. A primed constant infusion of stable isotopically labeled phenylalanine was administered to a homozygous apoE deficient subject. Kinetic parameters of apoB-100 and apoB-48 weredetermined by multicompartmental modeling. In the apoE deficient subject, fractional catabolic rates (FCR) of apoB-100 in VLDL and IDL, and apoB-48 in VLDL were 3, 12, and 12 times slower, respectively, than those of controls. The delayed catabolism of VLDL and IDL was due to the combination of absent direct removal and severely impaired conversion. On the other hand, the LDL apoB-100 FCR was increased by 2.6 times. Furthermore, the production rate of VLDL apoB-100 was decreased by 45% as compared with controls. In the Lp(a) kinetic study, two types of Lp(a) were isolated from plasma with apoE deficiency; buoyant and normal Lp(a) present at IDL and HDL density, respectively, and radiolabeled, then injected into the apoE subject and control subjects. 125I-buoyant Lp(a) was catabolized at a slower rate than in control subjects (residence time 3.85 vs 2.15 ± 0.33 days in control subject). However, 125I-buoyant Lp(a) was catabolized at twice as fast as 131I-normal Lp(a) in the control subjects (2.15 ± 0.33 vs 4.23 ± 0.20 days). In summary, apoE deficiency results in: 1) a markedly impaired catabolism of VLDL/chylomicron and their remnants due to lack of direct removal and impaired lipolysis, 2) an increased rate of catabolism of LDL apoB-100, due likely to up-regulation of LDL receptor activity, 3) reduced VLDL apoB production; and 4) a delayed catabolism of a portion of Lp(a).
Revised on April 19, 2004
Accepted on April 20, 2004
Abnormal in vivo metabolism of ApoB-containing lipoproteins in human ApoE deficiency
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Zheng, C. Khoo, K. Ikewaki, and F. M. Sacks Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions J. Lipid Res., May 1, 2007; 48(5): 1190 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nishiwaki, K. Ikewaki, G. Bader, H. Nazih, M. Hannuksela, A. T. Remaley, R. D. Shamburek, and H. B. Brewer Jr Human Lecithin:Cholesterol Acyltransferase Deficiency: In Vivo Kinetics of Low-Density Lipoprotein and Lipoprotein-X Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1370 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Devlin, S.-J. Lee, G. Kuriakose, C. Spencer, L. Becker, I. Grosskopf, C. Ko, L.-S. Huang, M. L. Koschinsky, A. D. Cooper, et al. An Apolipoprotein(a) Peptide Delays Chylomicron Remnant Clearance and Increases Plasma Remnant Lipoproteins and Atherosclerosis In Vivo Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1704 - 1710. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
