Studies on the metabolism of apolipoprotein B in hypertriglyceridemic subjects using simultaneous administration of tritiated leucine and radioiodinated very low density lipoprotein

W. F. Beltz, Y. A. Kesaniemi, N. H. Miller, W. R. Fisher, Scott M Grundy, L. A. Zech

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

To study the metabolic pathways of apolipoprotein B (apoB), a series of studies wre carried out in which both radioiodinated very low density lipoproteins (VLDL) and tritiated leucine were simulataneously injected into three hypertriglyceridemic subjects. The appearance and disappearance of tritium activity in VLDL apoB, intermediate density lipoprotein (IDL) apoB, and low density lipoprotein (LDL) apoB were followed as was the disappearance of iodine activity from VLDL and the appearance and disappearance of iodine activity in IDL apoB and LDL apoB. It was found that a delipidation chain could describe the kinetics of both endogenously and exogenously labeled VLDL. A slow component of VLDL was necessary to fit the VLDL 131I-labeled apoB data and was consistent with the observed VLDL [3H] apoB kinetics. In addition, the estimated rat of conversion of VLDL apoB to LDL exceeded that which appeared to pass through the measured IDL pools, suggesting that a fraction of the IDL was not directly observed. It was also found that a higher percentage of VLDL 131I-labeled apoB was converted to LDL apoB than was VLDL [3H] apoB. To evaluate possible causes of this apparent anomaly, simulataneous examination of all kineitc data was performed. This exercise resulted in the resolution of removal pathways from multiple compartments in the VLDL delipidation chain and the conversion of slowly metabolized VLDL to IDL and LDL. The wide spectrum of this loss pathway indicates that previous estimates of VLDL apoB production rate using the radioiodinated methodology probably represent lower bounds for the true physiologic variable. It is important to note that these direct losses were apparent only when the combination of endogenous and exogenous labeling was used.

Original languageEnglish (US)
Pages (from-to)361-374
Number of pages14
JournalJournal of lipid research
Volume31
Issue number3
StatePublished - Jan 1 1990

Keywords

  • SAAM
  • lipoprotein metabolism
  • multicompartmental modeling
  • tracer kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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