Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency

Katsunori Ikewaki; William Cain; Fairwell Thomas; Robert Shamburek; Loren A. Zech; David Usher; H. Bryan Brewer, Jr.; Daniel J. Rader

Journal of Lipid Research (Jul 2004)

Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency

Katsunori Ikewaki,
William Cain,
Fairwell Thomas,
Robert Shamburek,
Loren A. Zech,
David Usher,
H. Bryan Brewer, Jr.,
Daniel J. Rader

Affiliations

Katsunori Ikewaki: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
William Cain: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
Fairwell Thomas: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
Robert Shamburek: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
Loren A. Zech: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
David Usher: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
H. Bryan Brewer, Jr.: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160
Daniel J. Rader: Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; School of Life and Health Sciences, University of Delaware, Newark, DE 19716; Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan 105-8461; University of Pennsylvania Medical Center, 654 BREII/III 421 Curie Boulevard, Philadelphia, PA 19104-6160

Journal volume & issue: Vol. 45, no. 7
pp. 1302 – 1311

Abstract

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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).

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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