INVOLVEMENT OF THE LYSOSOME IN THE CATABOLISM OF INTRACELLULAR LYSOPHOSPHATIDYLCHOLINE AND EVIDENCE FOR DISTINCT POOLS OF LYSOPHOSPHATIDYLCHOLINE

The role of the lysosome in the metabolism of lysophosphatidylcholine was investigated in isolated rat hepatocytes. Chloroquine, primaquine, and ammonium chloride caused a 2.5-fold increase in radioactive lysop hosphatidylcholine in [methyl-H-3]choline-labeled cells. This effect w as confirmed by a 1.7-fold increase in lysophosphatidylcholine mass in chloroquine-treated hepatocytes. Chloroquine caused a 2.7-fold increa se in radioactive lysophosphatidylethanolamine in [1-H-3]ethanolamine- labeled cells and a 2.3-fold increase in radio-active lysophosphatidyl choline in [methyl-H-3]methionine-labeled cells. Chloroquine did not a ffect formation of choline-containing aqueous metabolites or the level of radioactivity in phosphatidylcholine (PC). The effect of chloroqui ne on radioactive lysophosphatidylcholine accumulation was concentrati on-dependent and occurred within 10 min, consistent with rapid inhibit ion of lysosomal function. As there was no observed decrease in the H- 3 in PC, the accumulation of lysophosphatidylcholine was likely due to the inhibition of acid lysophospholipase activity in chloroquine-trea ted cells. The accumulation of lysophosphatidylcholine in the presence of chloroquine was observed in both short-term- (30 min) and equilibr ium-(24 h) [methyl-H-3]choline-labeled cells. Simultaneous incubation of hepatocytes with both albumin and chloroquine increased the radioac tivity in lysophosphatidylcholine in the medium independently of the a ccumulation of radioactive lysophosphatidylcholine in the cells. The r esults suggest that there are separate pools of lysophosphatidylcholin e in the hepatocyte and that the pool donated to an extracellular acce ptor is different from the lysosomal pool. This study is the first to suggest that lysosomes are involved in the catabolism of intracellular lysophosphatidylcholine in isolated rat hepatocytes.