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.