Lysosomal Acid Lipase: Assay and Purification

Lysosomal acid lipase (LAL, E.C. 3.1.1.13) is a hydrolase involved in the intracellular degradation of lipoproteins. LAL was first described in fibroblasts (1 ), and since then found in all analyzed tissues with the exception of erythrocytes (2 ,3 ). The enzyme hydrolyzes cholesterol esters and triacylglycerols endocytosed by the cells and transferred to the lysosomal pathway. Cholesterol released by this reaction equilibrates with the cytoplasmic cholesterol pool and contributes to the regulation of intracellular lipid metabolism by three mechanisms: (1) free cholesterol reduces the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase, the key enzyme of cholesterol synthesis (4 ) (2) cholesterol activates its own esterification by acyl-CoA-cholesterol acyltransferase (5 ); and (3) cholesterol downregulates low-density lipoprotein receptor expression, which subsequently reduces cellular cholesterol uptake (6 ).