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

doi:10.1016/j.metabol.2015.10.031

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

Metabolism. 2016 Apr;65(4):381-90. doi: 10.1016/j.metabol.2015.10.031. Epub 2015 Nov 6.

Authors

Margaret R Diffenderfer¹, Stefania Lamon-Fava², Santica M Marcovina³, P Hugh R Barrett⁴, Julian Lel⁵, Gregory G Dolnikowski⁶, Lars Berglund⁷, Ernst J Schaefer⁸

Affiliations

¹ Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: [email protected].
² Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: [email protected].
³ Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, 401 Queen Anne Avenue North, Seattle, WA 98109, USA. Electronic address: [email protected].
⁴ School of Medicine and Pharmacology and Faculty of Engineering, Computing and Mathematics, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Electronic address: [email protected].
⁵ Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: [email protected].
⁶ Mass Spectrometry Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: [email protected].
⁷ Clinical and Translational Science Center, University of California, Davis, 2921 Stockton Boulevard, Suite 1400, Sacramento, CA 95817, USA. Electronic address: [email protected].
⁸ Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: [email protected].

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: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] 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 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).

Conclusion: Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) 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.

Keywords: Fed state; Hypertriglyceridemia; Kinetics; Lipoprotein(a).

MeSH terms

Apolipoprotein B-100 / biosynthesis
Apolipoprotein B-100 / blood
Apolipoprotein B-100 / metabolism*
Apolipoproteins A / biosynthesis
Apolipoproteins A / metabolism*
Dyslipidemias / blood
Humans
Hypertriglyceridemia / metabolism
Kinetics
Leucine / metabolism
Lipids / blood
Lipoprotein(a) / biosynthesis
Lipoprotein(a) / metabolism*
Male
Middle Aged

Substances

APOB protein, human
Apolipoprotein B-100
Apolipoproteins A
Lipids
Lipoprotein(a)
Leucine

Abstract

MeSH terms

Substances

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