Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency.
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 (13)C(6)-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 3x, 12x, and 12x slower than those of controls. On the other hand, the LDL apoB-100 FCR was increased by 2.6x. 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). (125)I-buoyant Lp(a) was catabolized at a slower rate in the patient. However, (125)I-buoyant Lp(a) was catabolized at twice as fast as (131)I-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).
Ikewaki
Katsunori
K
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. kikewaki@jikei.ac.jp
Cain
William
W
Thomas
Fairwell
F
Shamburek
Robert
R
Zech
Loren A
LA
Usher
David
D
Brewer
H Bryan
HB
Rader
Daniel J
DJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D016022:Case-Control Studies; D002914:Chylomicrons / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008661:Metabolism, Inborn Errors / Q000209:etiology / Q000378:metabolism*
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002914:Chylomicrons; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL