title: The metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein (a) in human beings.
abstract: The metabolism of apolipoproteins (apo) (a) and B-100 within plasma lipoprotein (a) [Lp(a)] was examined in the fed state in 23 subjects aged 41 to 79 years who received a primed-constant infusion of [5,5,5-2H3] leucine over 15 hours. Lipoprotein (a) was isolated from the whole plasma using a lectin affinity-based method. Apolipoprotein (a) and apoB-100 were separated by gel electrophoresis, and tracer enrichment of each apolipoprotein was measured using gas chromatography/mass spectrometry. Data were fit to a multicompartmental model to determine fractional catabolic rates (FCRs) and secretion rates (SRs). The FCRs of apo(a) and apoB-100 (mean +/- SEM) within plasma Lp(a) were significantly different (0.220 +/- 0.030 pool/d and 0.416 +/- 0.040 pool/d, respectively; P < .001). Apolipoprotein (a) SR (0.50 +/- 0.08 mg/[kg per d]) was significantly lower than that of apoB-100 SR (1.53 +/- 0.22 mg/[kg per d]; P < .001) of Lp(a). Plasma concentrations of Lp(a) were correlated significantly with both apo(a) SR and apoB-100 SR (r = 0.837 and r = 0.789, respectively; P < .001) and negatively with apo(a) FCR and Lp(a) apoB-100 FCR (r = -0.547 and r = -0.717, respectively; P < .01). These data implicate different metabolic fates for apo(a) and apoB-100 within Lp(a) in the fed state. We therefore hypothesize that apo(a) does not remain covalently linked to a single apoB-100 lipoprotein but that it rather reassociates at least once with another apoB-100 particle, probably newly synthesized, during its plasma metabolism.
authors.affiliation: Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Jenner
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Seman
authors.forename: John S
authors.initials: JS
authors.lastname: Millar
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.forename: Francine K
authors.initials: FK
authors.lastname: Welty
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Carl
authors.initials: C
authors.lastname: deLuca
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood*; D003903:Deuterium; D005260:Female; D005502:Food; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D007930:Leucine; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
chemical_list: D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D003903:Deuterium; D007930:Leucine