Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #176583
Title: THE METABOLISM OF APOLIPOPROTEINS (A) AND B-100 WITHIN PLASMA LIPOPROTEIN(A) IN HUMANS

Author
item JENNER, JENNIFER - TUFTS/HNRCA
item SEMAN, LEO - TUFTS/HNRCA
item MILLER, JOHN - UNIV OF PENNSYLVANIA
item Lamon-Fava, Stefania
item WELTY, FRANCINE - TUFTS/HNRCA
item Dolnikowski, Gregory
item MARCOVINA, SANTICA - N.W. LIPID RES LABS
item Lichtenstein, Alice
item BARRETT, P - WEST AUSTRALIA INST MED R
item DELUCA, CARL - TUFTS/HNRCA
item Schaefer, Ernst

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2004
Publication Date: 3/1/2005
Citation: Jenner, J.L., Seman, L.J., Miller, J.S., Lamon-Fava, S., Welty, F.K., Dolnikowski, G., Marcovina, S.M., Lichtenstein, A.H., Barrett, P.H., Deluca, C., Schaefer, E. 2005. The metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a) in humans. Metabolism. 54(3):361-369.

Interpretive Summary: Lipoprotein(a), of Lp(a), is a lipoprotein circulating in the bloodstream. Subjects with an elevated blood level of Lp(a) have an increased risk of developing coronary heart disease. Lp(a) contains two proteins, apo B100 and apo(a). The purpose of the current study was to evaluate the rate of production and clearance of these individual proteins in Lp(a). Twenty-three subjects were studied using a methodology that requires an IV infusion for 15 hours with a stable isotope-labeled amino acid, which allows the determination of the fractional catabolic rate (FCR) of a protein. Our study indicated that the FCRs of apo(a) and apoB-100 (mean+/-SEM) within plasma Lp(a) were significantly different (0.220 +/- 0.030 pool/day and 0.416 +/- 0.040 pool/day, respectively; p<0.001). Also, the synthetic rate of apo(a) (0.50 +/- 0.08 mg/kg/day) was significantly lower than that of apoB-100 (1.53 +/- 0.22 mg/kg/day; p < 0.001) in Lp(a). These results indicate that the two protein components of Lp(a) do not follow the same metabolic fate. It is likely that each molecule of apo(a), during its lifespan, subsequently associates with at least two different apo B100 particles.

Technical 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. Apo(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 multi-compartmental model to determine fractional catabolic rates (FCR) and secretion rates (SR). The FCRs of apo(a) and apoB-100 (mean +/- SEM) within plasma Lp(a) were significantly different (0.220 +/-0.030 pool/day and 0.416 +/-0.040 pool/day, respectively; p<0.001). Apo(a) SR (0.50 +/-0.08 mg/kg/day) was significantly lower than that of apoB-100 SR (1.53 +/-0.22 mg/kg/day; p < 0.001) of Lp(a). Plasma concentrations of Lp(a) were significantly correlated with both apo(a) SR and apoB-100 SR (r = 0.837 and r = 0.789, respectively; p < 0.001), and negatively with apo(a) FCR and Lp(a) apoB-100 FCR (r=-0.547 and r = - 0.717, respectively; p < 0.01). 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 rather, it re-associates at least once with another apoB-100 particle, probably newly synthesized, during its plasma metabolism.