Reactome | SOAT1,2 transfer acyl group to CHOL forming CHEST

SOAT1,2 transfer acyl group to CHOL forming CHEST

Stable Identifier

R-HSA-8876696

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, cytosol

ReviewStatus

5/5

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SOAT1,2 transfer acyl group to CHOL forming CHEST

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Excess cellular cholesterol (CHOL) is esterified and stored as cholesteryl ester (CHEST). The conversion is catalysed by the ER membrane-residing sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT 2, aka acyl-coenzyme A:cholesterol acyltransferase 1 and 2, ACAT1 and 2) (Chang et al. 1993, Oelkers et al. 1998, Lin et al. 1999). CHESTs are usually present at low levels in most cells but chronic accumulation of CHEST in macrophages causes these cells to appear foamy and is a characteristic of early stage atherosclerosis (Becker et al. 1994). The SOAT enzymes are being investigated as potential drug targets for atherosclerosis and for Alzheimer's disease (Chang et al. 2009). Alzheimer's disease is a prevalent neurodegenerative disease, characterised by a large extracellular accumulation of amyloid plaques, composed mainly of beta-amyloid peptide aggregates. Increases in free cholesterol in the membrane, which can be caused by inhibiting ACAT1, can lead to the decrease of amyloid precursor protein processing. Pharmacological inhibitors of ACAT1 are potential treatment routes for Alzheimer's disease (Puglielli et al. 2001, Chang et al. 2009, Zhu et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
10438503	Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains Chang, TY, Chen, J, Cheng, D, Lin, S, Liu, MS	J. Biol. Chem.	1999
8049197	Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase Lackner, KJ, Schmitz, G, Fehringer, P, Böttcher, A, Becker, A, Aslanidis, C, Notka, F	Arterioscler. Thromb.	1994
11584272	Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide Chang, TY, Konopka, G, Tanzi, RE, Berezovska, O, Ingano, LA, Kovacs, DM, Hyman, BT, Puglielli, L, Pack-Chung, E	Nat. Cell Biol.	2001
26474739	ACAT1 regulates the dynamics of free cholesterols in plasma membrane which leads to the APP-α-processing alteration Guo, D, Song, B, Xiong, Y, Li, Q, Li, B, Zhao, X, Xu, J, Zhu, M, Chang, CC, Hu, G, Chang, T, Zhang, X, Chen, J	Acta Biochim. Biophys. Sin. (Shanghai)	2015
19141679	Acyl-coenzyme A:cholesterol acyltransferases Li, BL, Urano, Y, Chang, TY, Chang, CC	Am. J. Physiol. Endocrinol. Metab.	2009
9756920	Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes Billheimer, JT, Behari, A, Sturley, SL, Oelkers, P, Cromley, D	J Biol Chem	1998
8407899	Molecular cloning and functional expression of human acyl-coenzyme A:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells Chang, TY, Chang, CC, Huh, HY, Cadigan, KM	J. Biol. Chem.	1993