Lysosomal Acid Lipase
Lysosomal acid lipase is responsible for the acid lipolysis of cellular lipid stores, breaking down cholesteryl esters and triglycerides. Mutations in the gene for LAL (LIPA) lead to lysosomal storage disorders, and changes in LAL activity have been linked to atherosclerosis.
Lysosomal Acid Lipase Inhibitors |
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|---|---|
| Cat. No. | 产品名称/活性 |
| 6098 | Lalistat 1 |
| Potent and selective LAL inhibitor | |
| 6099 | Lalistat 2 |
| Selective LAL inhibitor | |
Lysosomal acid lipase (LAL) EC 3.1.1.13 is an enzyme responsible for the breakdown of cholesteryl esters and triglycerides in lysosomes and is encoded by the Lipase A, lysosomal acid type (LIPA) gene. LAL plays a key role in lipophagy and mutations in the LIPA gene lead to lysosomal storage disorders.
Following internalization of lipoprotein particles via receptor mediated endocytosis, LAL catalyzes the hydrolysis of cholesteryl esters and triglycerides. This process produces free cholesterol and fatty acids, which are required by the body as components in all cell membranes; precursors for oxysterol, steroid hormones and bile acids; and in vitamin D synthesis. The activity of LAL requires the acidic environment of lysosomes (pH 3.5 - 4.5) and is inhibited by the increase in pH caused by free cholesterol build up within lysosomes.
Mutations in LIPA lead to lysosomal storage disorders: a reduction in expression with some remaining enzyme activity results in cholesteryl ester storage disease (CESD), whereas complete lack of LAL activity causes Wolman disease, characterised by digestive problems and failure to thrive in infants. Additionally, as a key enzyme in acid lipolysis of cellular lipid stores, LAL plays a fundamental role in lipophagy (a subtype of autophagy). The misregulation of lipophagy is associated with a variety of diseases including lysosomal storage disorders, atherosclerosis and obesity.