Cholesterol ester and triglyceride metabolism in intact fibroblasts from patients with Wolman's disease and cholesterol ester storage disease.
Cholesterol ester and triglyceride metabolism was examined in intact fibroblast monolayers from normal individuals and patients with Wolman's disease and cholesterol ester storage disease. Cholesterol esters were introduced into cells by incubation in medium containing [3H]cholesteryl linoleate (CL) bound to human low density lipoprotein. Triglycerides were introduced by incubation with glycerol tri[1-14C]oleate (triolein) bound to human very low-density lipoprotein. Both types of mutant cell lines accumulated the unhydrolyzed substrates to a greater extent than did normal cells with the greatest accumulation observed in Wolman's disease cells. Wolman's disease cells hydrolyzed CL at 10-22% and triolein at 11-19% the rate of normal cells; cholesterol ester storage disease cells hydrolyzed these substrates at 28-49 and 30-47% the normal rate, respectively. In contrast, assays of acid lipase activity in cell lysates revealed less than 1% of control activity in both disorders. The data suggest that the mutant acid lipase present in Wolman's disease and cholesterol ester storage disease is more active in the intact cell than assays of cell lysates would indicate. In addition, the differences observed between the two disorders provide a biochemical explanation for the different phenotypes associated with the two disorders.
D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000172:deficiency; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008049:Lipase