SOAT1,2 transfer acyl group to CHOL forming CHEST

Stable Identifier
R-HSA-8876696
Type
Reaction [transition]
Species
Homo sapiens
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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
8049197 Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase

Becker, A, Böttcher, A, Lackner, KJ, Fehringer, P, Notka, F, Aslanidis, C, Schmitz, G

Arterioscler. Thromb. 1994
10438503 Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains

Lin, S, Cheng, D, Liu, MS, Chen, J, Chang, TY

J. Biol. Chem. 1999
11584272 Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide

Puglielli, L, Konopka, G, Pack-Chung, E, Ingano, LA, Berezovska, O, Hyman, BT, Chang, TY, Tanzi, RE, Kovacs, DM

Nat. Cell Biol. 2001
26474739 ACAT1 regulates the dynamics of free cholesterols in plasma membrane which leads to the APP-α-processing alteration

Zhu, M, Zhao, X, Chen, J, Xu, J, Hu, G, Guo, D, Li, Q, Zhang, X, Chang, CC, Song, B, Xiong, Y, Chang, T, Li, B

Acta Biochim. Biophys. Sin. (Shanghai) 2015
19141679 Acyl-coenzyme A:cholesterol acyltransferases

Chang, TY, Li, BL, Chang, CC, Urano, Y

Am. J. Physiol. Endocrinol. Metab. 2009
9756920 Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes

Oelkers, P, Behari, A, Cromley, D, Billheimer, JT, Sturley, SL

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, CC, Huh, HY, Cadigan, KM, Chang, TY

J. Biol. Chem. 1993
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Title
cholesterol O-acyltransferase activity of SOAT1,2 [endoplasmic reticulum membrane]
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