Degradation of lysophosphatidylcholine by lysosomes. Stimulation of lysophospholipase C by taurocholate and deficiency in Niemann-Pick fibroblasts.

Hydrolysis of 2-[1-14C]oleoyl phosphatidylcholine and of 1-[1-14C]oleoyl lysophosphatidylcholine by lysosomes prepared from rat liver using Triton WR-1339 has been studied. At pH 5.0 sodium taurocholate stimulated the release by the soluble lysosomal fraction of labelled lysophosphatidylcholine, diacyl- and monoacylglycerol and fatty acids from [14C]phosphatidylcholine. The time course of appearance of labelled products suggested that monoacylglycerol could be released as a result of the action of phospholipase A1 followed by lysophospholipase C or by the initial action of phospholipase C followed by monoacylglycerol lipase. The hydrolysis of 1-[14C]acyl lysophosphatidylcholine was also stimulated by sodium taurocholate under similar conditions; however, only release of monoacylglycerol was increased, whereas release of fatty acid was inhibited. Mg2+ inhibited the release of labelled monoacylglycerol and of fatty acid from lysophosphatidylcholine. The detergents deoxycholate and Triton X-100 and phospholipids were strongly inhibitory. 5'-AMP almost completely suppressed release of monoacylglycerol but increased release of fatty acid. Chloroquine strongly suppressed release of monoacylglycerol and only at high concentration (1.25 mM) diminished fatty acid release. In the presence of sodium taurocholate the predominant mechanism for degradation of phosphatidylcholine by the soluble fraction of lysosomes involves phospholipase A followed by phospholipase C. Assay of release of monoacylglycerol from [14C]lysophosphatidylcholine catalyzed by extracts of fibroblasts from patients with Niemann-Pick disease and controls in the presence of taurocholate revealed that lysophospholipase C activity was lacking in those cell lines that were deficient in sphingomyelinase. This suggests that lysophospholipase C and sphingomyelinase activities may be catalyzed by one enzyme.