文章基本信息

标题：Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency
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作者：Katsunori Ikewaki ; William Cain ; Fairwell Thomas 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2004
卷号：45
期号：7
页码：1302-1311
DOI：10.1194/jlr.M400020-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The present study was undertaken to elucidate the metabolic basis for the increased remnants and lipoprotein(a) [Lp(a)] and decreased LDL apolipoprotein B (apoB) levels in human apoE deficiency. A primed constant infusion of ¹³C₆-phenylalanine was administered to a homozygous apoE-deficient subject. apoB-100 and apoB-48 were isolated, and tracer enrichments were determined by gas chromatography-mass spectrometry, then kinetic parameters were calculated by multicompartmental modeling. In the apoE-deficient subject, fractional catabolic rates (FCRs) of apoB-100 in VLDL and intermediate density lipoprotein and apoB-48 in VLDL were 3×, 12×, and 12× slower than those of controls. On the other hand, the LDL apoB-100 FCR was increased by 2.6×. The production rate of VLDL apoB-100 was decreased by 45%. In the Lp(a) kinetic study, two types of Lp(a) were isolated from plasma with apoE deficiency: buoyant and normal Lp(a). ¹²⁵I-buoyant Lp(a) was catabolized at a slower rate in the patient. However, ¹²⁵I-buoyant Lp(a) was catabolized at twice as fast as ¹³¹I-normal Lp(a) in the control subjects. 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, likely due to upregulation of LDL receptor activity; 3) reduced VLDL apoB production; and 4) a delayed catabolism of a portion of Lp(a).