Abstract
The interaction of lysosomal cholesterol esterase with liposome-CHL-E composed of PC and PE at various ratios was investigated. Liposomes were prepared by sonicating lyophilized cholesteryl-1-[14C]-oleate with phospholipids (1: 66) at various ratios of PC to PE (PC only, 25, 10, 3, 1, 0.5). Rat liver lysosomal fraction, guinea pig peritoneal macrophages and the ring of rat thoracic aorta were used to examine the interaction of the liposomes with the enzyme, cells and tissues, respectively. The hydrolytic rates of liposome-CHL-E by cholesterol esterase in rat liver lysosomal fraction were markedly changed with varying ratios of PC to PE in the liposomes. The largest Vmax and the smallest Km were obtained with the liposome with the ratio of PC/PE: 1. Vmax and Km were getting less and greater, respectively, in the order of the ratio: 1, 0.5, 3, 10 and 25.
The uptake and degradation of liposome-CHL-E by guinea pig peritoneal macrophages during 24hr incubation, was greatest in the liposome with the ratio 1, followed by those with the ratio: 0.5, 3, and 10, 25, PC only. However, the rate of degradation of liposome-CHL-E to the uptake was in almost the same degree with various liposomes. A similar result was obtained when the liposomes were incubated with rabbit aortic ring preparation, in which the rate of the degradation was less than in the macrophages, especially of the liposomes with the ratios larger than 10.
The ratio of PC/PE in VLDL-LDL fraction of cholesterol fed-rabbit serum was analyzed to examine if a change in the ratio would occur during atherogenesis. PC/PE ratios were getting greater with an increase in cholesterol level in the fraction, and there was a significant linear correlation between them (r=0.507). These results suggest that the metabolic rate of LDL-CHL-E, a native substrate for cholesterol esterase, changes with the composition of phospholipids in the particles, and that the change in the composition in LDL will occur in certain pathological conditions.
