The catabolism of alpha 2- and
beta-very-low-density lipoproteins (VLDL) was studied in normolipidemic and hyperlipidemic subjects to determine whether differences in the catabolism of these subfractions are due to their composition. alpha 2-VLDL (
cholesterol/
triglyceride ratio, 00.18 +/- 0.06; and
apoprotein E/C ratio, 0.27 +/- 0.22, n = 4) and
beta-VLDL (
cholesterol/
triglyceride ratio, 0.67 +/- 0.13; and
apoprotein E/C ratio, 1.05 +/- 0.52, n = 4) were isolated from subjects with
broad beta disease, iodinated, and injected in five normolipidemic subjects, six with
broad beta disease, and five with endogenous
hypertriglyceridemia. VLDL, intermediate (IDL) and
low-density lipoprotein (
LDL)
apoprotein (
apo)-B radioactivity (
tetramethylurea insoluble) following injection of 125I-labeled alpha 2- and
beta-VLDL decayed biphasically in all subjects, and this decay in normolipidemic subjects was more rapid than in subjects with
broad beta disease (P = 0.004) or endogenous
hypertriglyceridemia (P = 0.004 for alpha 2- and P = 0.010 for
beta-VLDL). The residence times, however, for the delipidation chain in alpha 2-VLDL were similar in all the subjects and varied from three to six hours. The decay of radioactivity in
beta-VLDL in subjects with
broad beta disease was much slower (residence time, 36.9 +/- 24.4 hr, n = 7) than in normolipidemic subjects (residence time, 7.56 +/- 4.6 hr, n = 5) or in subjects with endogenous
hypertriglyceridemia (residence time, 10.6 +/- 4.65, n = 4). The residence time for alpha 2-VLDL was longer than for
beta-VLDL in all subjects, suggesting that alpha 2-VLDL is a precursor to
beta-VLDL. To test this directly, iodinated alpha 2-VLDL was injected into a subject with
broad beta disease and the radioactivity in the subfractions was followed. The radioactivity from alpha 2-VLDL was transferred into
beta-VLDL supporting, the notion that alpha 2-VLDL generated some
beta-VLDL.
Nicotinic acid treatment of a subject with
broad beta disease accelerated the catabolism of alpha 2- and
beta-VLDL without changing the VLDL composition.