Reaction: LIPA hydrolyses sterol esters to sterols and fatty acids
- in pathway: LDL clearance
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).
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).
Reaction - small molecule participants:
CHOL [lysosomal lumen]
FA [lysosomal lumen]
H2O [lysosomal lumen]
Reactome.org reaction link: R-HSA-8865667
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Reaction input - small molecules:
water
Reaction output - small molecules:
cholesterol
fatty acid
Reactome.org link: R-HSA-8865667