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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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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Apoprotein(a)
Lipoprotein(a)
Apolipoprotein B-100
Dyslipidemias
Leucine
Gas Chromatography-Mass Spectrometry
Electrophoresis
Gels

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., ... 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

Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a). / Diffenderfer, Margaret R.; Lamon-Fava, Stefania; Marcovina, Santica M.; Barrett, P. Hugh R; Lel, Julian; Dolnikowski, Gregory G.; Berglund, Lars; Schaefer, Ernst J.

In: Metabolism: Clinical and Experimental, Vol. 65, No. 4, 01.04.2016, p. 381-390.

Research output: Contribution to journalArticle

Diffenderfer, MR, Lamon-Fava, S, Marcovina, SM, Barrett, PHR, Lel, J, Dolnikowski, GG, Berglund, L & Schaefer, EJ 2016, 'Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a)', Metabolism: Clinical and Experimental, vol. 65, no. 4, pp. 381-390. https://doi.org/10.1016/j.metabol.2015.10.031
Diffenderfer MR, Lamon-Fava S, Marcovina SM, Barrett PHR, Lel J, Dolnikowski GG et al. Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a). Metabolism: Clinical and Experimental. 2016 Apr 1;65(4):381-390. https://doi.org/10.1016/j.metabol.2015.10.031
Diffenderfer, Margaret R. ; Lamon-Fava, Stefania ; Marcovina, Santica M. ; Barrett, P. Hugh R ; Lel, Julian ; Dolnikowski, Gregory G. ; Berglund, Lars ; Schaefer, Ernst J. / Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a). In: Metabolism: Clinical and Experimental. 2016 ; Vol. 65, No. 4. pp. 381-390.
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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.",
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AU - Diffenderfer, Margaret R.

AU - Lamon-Fava, Stefania

AU - Marcovina, Santica M.

AU - Barrett, P. Hugh R

AU - Lel, Julian

AU - Dolnikowski, Gregory G.

AU - Berglund, Lars

AU - Schaefer, Ernst J.

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N2 - 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.

AB - 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.

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KW - Hypertriglyceridemia

KW - Kinetics

KW - Lipoprotein(a)

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