Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a)

Margaret R. Diffenderfer, Stefania Lamon-Fava, Santica M. Marcovina, P. Hugh R Barrett, Julian Lel, Gregory G. Dolnikowski, Lars Berglund, Ernst J. Schaefer

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Abstract

Objectives Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). Materials and Methods The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7 nmol/L]. All subjects received a primed constant infusion of [5,5,5-2H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Results Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P = 0.04). The median Lp(a) apo(a) production rate at 0.248 nmol/kg · day-1 was significantly lower than that of Lp(a) apoB-100 at 0.514 nmol/kg · day-1 (P = 0.03). Conclusion Our data indicate that apo(a) has a plasma residence time (11 days) that is more than twice as long as that of apoB-100 (4 days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalMetabolism: Clinical and Experimental
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2016

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Keywords

  • Fed state
  • Hypertriglyceridemia
  • Kinetics
  • Lipoprotein(a)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Endocrinology

Cite this

Diffenderfer, M. R., Lamon-Fava, S., Marcovina, S. M., Barrett, P. H. R., Lel, J., Dolnikowski, G. G., Berglund, L., & Schaefer, E. J. (2016). Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a). Metabolism: Clinical and Experimental, 65(4), 381-390. https://doi.org/10.1016/j.metabol.2015.10.031