Lipase A, lysosomal acid type

LIPA
Identifiers
Aliases	LIPA, CESD, LAL, lipase A, lysosomal acid type
External IDs	OMIM: 613497; MGI: 96789; HomoloGene: 37277; GeneCards: LIPA; OMA:LIPA - orthologs
Gene location (Human) Chr. Chromosome 10 (human) Band 10q23.31 Start 89,213,569 bp End 89,414,557 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19|19 C1 Start 34,469,718 bp End 34,504,874 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa duodenum corpus callosum visceral pleura C1 segment monocyte inferior ganglion of vagus nerve spleen trabecular bone lymph node Top expressed in left lobe of liver stroma of bone marrow right kidney human kidney calvaria thymus ciliary body lumbar spinal ganglion duodenum genital tubercle More reference expression data BioGPS n/a
Gene ontology Molecular function hydrolase activity hydrolase activity, acting on ester bonds lipase activity sterol esterase activity Cellular component lysosome fibrillar center lysosomal lumen intracellular membrane-bounded organelle Biological process lipid catabolic process homeostasis of number of cells within a tissue cytokine production cell population proliferation inflammatory response tissue remodeling cell morphogenesis lung development lipid metabolism low-density lipoprotein particle clearance sterol metabolic process cellular lipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3988 16889 Ensembl ENSG00000107798 ENSMUSG00000024781 UniProt P38571 Q9Z0M5 RefSeq (mRNA) NM_000235 NM_001127605 NM_001288979 NM_001111100 NM_021460 RefSeq (protein) NP_000226 NP_001121077 NP_001275908 NP_001104570 NP_067435 Location (UCSC) Chr 10: 89.21 – 89.41 Mb Chr 19: 34.47 – 34.5 Mb PubMed search
Wikidata
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Lipase A, lysosomal acid type is a protein that in humans is encoded by the LIPA gene.

Function

This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase or LAL). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides, leading to the production of free cholesterol and fatty acids. Notably, LAL is the only known acid lipase that hydrolyzes cholesteryl esters and triglycerides within the lysosomal environment.

LAL is essential to intracellular lipid metabolism in macrophages and hepatocytes. Upon uptake of LDL by endocytosis, cholesteryl esters and triglycerides are transported to lysosomes where they are hydrolyzed by LAL. The resulting free cholesterol either exits the lysosome for future use in membrane synthesis or is re-esterified in the endoplasmic reticulumby ACAT to form lipid droplets. This process is important for foam cell formation during atherogenesis.

The importance of LAL in cardiovascular disease has been highlighted by GWAS studies, which have identified variants in the LIPA locus that are associated with coronary artery disease. LAL was found to have high expression in macrophages located in atherosclerotic plaques, where its activity contributes to the accumulation of lipid droplets and the progression of plaque development.

Schematic overview of LAL function in lipid metabolism. LDL is hydrolyzed by LAL in the lysosome, producing free cholesterol, which either leaves the cell or is re-esterified in the endoplasmic reticulum by ACAT to form lipid droplets, the foundation of foam cells.

Mutations in the LIPA gene that cause loss-of-function can result in infant-onset Wolman disease, caused by a complete lack of LAL production, or a later-onset Cholesterol ester storage disease (CESD), caused by a 5-10% reduction in LAL production.

Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014].

Further reading

• Riemenschneider M, Mahmoodzadeh S, Eisele T, Klopp N, Schwarz S, Wagenpfeil S, Diehl J, Mueller U, Foerstl H, Illig T, Kurz A (2004). "Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease". Neurobiol. Aging. 25 (10): 1305–8. doi:10.1016/j.neurobiolaging.2004.01.001. PMID 15465627. S2CID 43039824.
• Papassotiropoulos A, Wollmer MA, Tsolaki M, Brunner F, Molyva D, Lütjohann D, Nitsch RM, Hock C (July 2005). "A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease". J Clin Psychiatry. 66 (7): 940–7. doi:10.4088/JCP.v66n0720. PMID 16013913.
• Zhao B, Fisher BJ, St Clair RW, Rudel LL, Ghosh S (October 2005). "Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to lipid droplets upon lipid loading". J. Lipid Res. 46 (10): 2114–21. doi:10.1194/jlr.M500207-JLR200. PMID 16024911.
• Zhao B, Natarajan R, Ghosh S (November 2005). "Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis". Physiol. Genomics. 23 (3): 304–310. CiteSeerX 10.1.1.861.6660. doi:10.1152/physiolgenomics.00187.2005. PMID 16131527.
• Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrièze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O'Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A (January 2006). "A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease". Am. J. Hum. Genet. 78 (1): 78–88. doi:10.1086/498851. PMC 1380225. PMID 16385451.
• von Trotha KT, Heun R, Schmitz S, Lütjohann D, Maier W, Kölsch H (July 2006). "Influence of lysosomal acid lipase polymorphisms on chromosome 10 on the risk of Alzheimer's disease and cholesterol metabolism". Neurosci. Lett. 402 (3): 262–6. doi:10.1016/j.neulet.2006.04.009. PMID 16730122. S2CID 8354106.
• Wang F, Wang W, Wähälä K, Adlercreutz H, Ikonen E, Tikkanen MJ (December 2008). "Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters" (PDF). Am. J. Physiol. Endocrinol. Metab. 295 (6): E1455–61. doi:10.1152/ajpendo.90527.2008. PMID 18796546. S2CID 18294238. Archived from the original (PDF) on 2019-02-28.
• Ruaño G, Bernene J, Windemuth A, Bower B, Wencker D, Seip RL, Kocherla M, Holford TR, Petit WA, Hanks S (February 2009). "Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone". Clin. Chim. Acta. 400 (1–2): 48–55. doi:10.1016/j.cca.2008.10.009. PMID 18996102.
• Pisciotta L, Fresa R, Bellocchio A, Pino E, Guido V, Cantafora A, Di Rocco M, Calandra S, Bertolini S (June 2009). "Cholesteryl Ester Storage Disease (CESD) due to novel mutations in the LIPA gene". Mol. Genet. Metab. 97 (2): 143–8. doi:10.1016/j.ymgme.2009.02.007. PMID 19307143.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.