Human triglyceride-rich lipoprotein apo E kinetics and its relationship toLDL apo B-100 metabolism

Apolipoprotein (apo) E is a multifunctional protein that can act as a ligan d for lipoprotein receptors. The receptor-mediated clearance of the triglyc eride-rich lipoproteins (TRL) chylomicrons and VLDL from plasma is, in part , dependent on apo E. Enrichment of VLDL with apo E is thought to enhance r eceptor-mediated clearance of VLDL resulting in a low rate of conversion of VLDL to LDL. However. the kinetic mechanism controlling the concentration of apo E in VLDL is not known. We conducted kinetic studies on apo E in the TRL fraction (d < 1,006 g/ml) and apo B-100 in the TRL acid LDL (d = 1.019 -1.063 g/ml) fractions to assess the kinetic determinants of apo E concentr ation in TRL and to determine the effects that TRL apo E production and cle arance rates have on the production rate of LDL apo B-100. Nineteen males b etween the ages of 24 and 73 underwent a primed-constant infusion with deut erated leucine tracer in the constantly-fed state. Apo B-LOO from TRL and L DL, and apo E from TRL were isolated and their tracer incorporation measure d by gas chromatography;mass spectrometry. The residence time and productio n rates of each protein were determined from the kinetic data using, the SA AM II modeling program. The residence time and production rate of TRL apo E were about one-half that of TRL apo B-100 (1.8 <plus/minus> 1.0 vs. 2.9 +/ - 2.1 h and 14.5 +/- 11.0 vs. 27.6 +/- 17.3 mg/kg per day, respectively). T he production rate of TRL apo E was weakly correlated with the production r ate of TRL apo B-100 (r = 0.324, P = 0.07). Multiple regression analysis sh owed that the residence time of TRL apo B-100 and the relative TRL apo E pr oduction rate (relative to the TRL apo B100 production rate) were negativel y associated with LDL apo B-100 production rate, accounting for 68% of its variability. We conclude that (1) the concentration of apo E in TRL is high ly correlated to its production rate, suggesting that production rate regul ates the TRL apo E concentration. and (2) individuals with a relatively sho rt TRL apo B-100 residence time and those producing TRL with a relatively l ow apo E content have: the highest LDL apo B-100 production rates. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.