Metabolism of C - apolipoproteins : kinetics of C - 11 , C - llll and C - Il 12 , and VLDL - apolipoprotein B in normal and hyperlipoproteinemic subjects

The turnover and metabolism of the individual C apolipoproteins (C-11, C-IIIl, and C-I&) were studied following the injection of 1251-labeled VLDL into 15 normal and hyperlipoproteinemic subjects. The C apolipoproteins from very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were separated by analytical isoelectric focusing, and subsequent densitometric scanning and radioassay of the stained bands yielded values for specific activity. In 13 of 15 subjects, kinetics of C-11, C-IIIl, and C-111, were best described by a one-pool model, whereas two subjects showed biexponential kinetics. The specific activity-time curves for VLDL and HDL were superimposable, indicating rapid exchange of all C apolipoproteins in hyperlipidemic as well as in normal subjects. In each subject the half-life was similar for C-11, C-HI,, and C-II12, which suggests similar synthesis and catabolic mechanisms for each C apo1ipoprotein.g The mass of exchangeable C-I1 (range 1.0-5.8 mg/kg), C-III1 (2.6-20 mg/kg), and C-111, (2.0-13 mg/kg) increased with plasma triglyceride concentrations. Values for flux of C-I1 were 1.02.8 mg/d per kg, for C-111, 1.6-5.6 mgid per kg, and for C-111, 1.2-3.1 mg/d per kg, but they were not related to levels of plasma triglyceride. However the irreversible fractional catabolic rates were inversely related to C apolipoprotein (and triglyceride) mass, suggesting that expansion in C apolipoprotein pool size is related to slower removal, due t o the longer residence time of triglyceride-rich VLDL particles in plasma. This was confirmed by similar findings for B apolipoprotein kinetics in VLDL carried out simultaneously.-Huff, M. W., N. H. Fidge, P. J. Nestel, T. Billington, and B. Watson. Metabolism of C-apolipoproteins: kinetics of C-11, (2-111, and C-III,, and VLDLapolipoprotein B in normal and hyperlipoproteinemic subjects. J . Lipid Res. 198 1. 22: 12351246. Supplementary key words VLDI. . HDL . isoelectric focusing T h e C group of apolipoproteins consists of small molecular weight peptides apoC-I, apoC-11, and apoC-111. Together, the C-apolipoproteins make up approximately 50% and 10% of VLDL and HDL proteins, respectively, and in normal subjects a re equally distributed between VLDL and HDL (1, 2 ) . Of the C group of apolipoproteins, apoC-I1 has been shown to be a potent activator of lipoprotein lipase ( 3 ) . Its central role in lipoprotein catabolism has been demonstrated by Breckenridge et al. (4) who reported a subject with apoC-I1 deficiency and severe hypertriglyceridemia. ApoC-I is thought to be an activator of a specific lipoprotein lipase ( 5 ) and to stimulate the activity of 1ecithin:cholesterol acyltransferase (6), an enzyme which, like lipoprotein lipase, has a crucial role in lipoprotein lipid transport. Little is known of the function of the C-I11 group of peptides which contain between zero and two or more sialic acid residues per mole of protein (7), and are denoted as C-III,,, C-III', etc. ApoC-I11 has been reported to inhibit lipoprotein lipase in vitro (8, 9). Shelburne et al. (10) have shown that human apoCI11 inhibits the apoE-stimulated uptake of rat lymph chylomicrons in an isolated rat liver perfusion system. However Windler, Chao, and Have1 (1 1) have shown that rat apoC-111, as well as rat apoC-11, is equally effective in inhibiting the hepatic clearance of rat lymph chylomicrons. The role of apoC-111 has been more difficult o assess in vivo, although reports suggest that the ratio of apoC-I1 to apoC-I11 modulates the catabolism of triglyceride-rich lipoproteins (12, 13). Furthermore, the distribution of C peptides between HDL and triglyceride-rich particles is different in normolipidemic and hypertriglyceridemic