Reactome | LIPA hydrolyses sterol esters to sterols and fatty acids

LIPA hydrolyses sterol esters to sterols and fatty acids

Stable Identifier

R-HSA-8865667

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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LIPA hydrolyses sterol esters to sterols and fatty acids

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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
25699256	Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism Francis, GA, Dubland, JA	Front Cell Dev Biol	2015
8112342	Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase Ameis, D, Eckerskorn, C, Merkel, M, Greten, H	Eur. J. Biochem.	1994
9705237	Molecular and enzymatic analyses of lysosomal acid lipase in cholesteryl ester storage disease Sheriff, S, Du, H, Bezerra, J, Grabowski, GA, Leonova, T	Mol. Genet. Metab.	1998
8146180	Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease Coates, PM, Byrum, RS, Sando, GN, Anderson, RA	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 Sando, GN, Anderson, RA	J. Biol. Chem.	1991