LIPA hydrolyses sterol esters to sterols and fatty acids

Stable Identifier
R-HSA-8865667
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Lysosomal acid lipase/cholesteryl ester hydrolase (LIPA, aka lysosomal acid lipase, LAL) is structurally related to previously described enteric acid lipases and catalyses the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins (LDLs) (Anderson & Sando 1991, Ameis et al. 1994). LIPA is catalytically active in monomeric form. Defects in LIPA can cause Wolman disease (WOD; MIM:278000), a lysosomal lipid storage disorder where cholesteryl esters and triglycerides accumulate in most tissues of the body. WOD occurs in infancy and is nearly always fatal before the age of 1 (Anderson et al. 1994, Du et al. 1998).

Atherosclerosis is characterised by the accumulation of excess cholesterol in the artery wall. In later stages of atherosclerosis, both free cholesterol and cholesteryl ester droplets accumulate within the lysosome. As the cholesterol level increases, it inhibits the proton pumping ability of the vATPases, the pH inside the lysosome increases and renders LIPA catalytically inactive, contributing further to the progression of atherosclerosis (Dubland & Francis 2015).

Literature References
PubMed ID Title Journal Year
8112342 Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase

Ameis, D, Merkel, M, Eckerskorn, C, Greten, H

Eur. J. Biochem. 1994
25699256 Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism

Dubland, JA, Francis, GA

Front Cell Dev Biol 2015
9705237 Molecular and enzymatic analyses of lysosomal acid lipase in cholesteryl ester storage disease

Du, H, Sheriff, S, Bezerra, J, Leonova, T, Grabowski, GA

Mol. Genet. Metab. 1998
8146180 Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease

Anderson, RA, Byrum, RS, Coates, PM, Sando, GN

Proc. Natl. Acad. Sci. U.S.A. 1994
1718995 Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase. Similarities to gastric and lingual lipases

Anderson, RA, Sando, GN

J. Biol. Chem. 1991
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
sterol esterase activity of LIPA [lysosomal lumen]
Physical Entity
Activity
Orthologous Events
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Reviewed
Created