Sterol O-acyltransferase

Short description: Class of enzymes

sterol O-acyltransferase

Identifiers
EC number| 2.3.1.26
CAS number| 9027-63-8
Databases
IntEnz| IntEnz view
BRENDA| BRENDA entry
ExPASy| NiceZyme view
KEGG| KEGG entry
MetaCyc| metabolic pathway
PRIAM| profile
PDB structures| RCSB PDB PDBe PDBsum
Gene Ontology| AmiGO  / QuickGO
| Search

PMC| articles
PubMed| articles
NCBI| proteins
sterol O-acyltransferase 1

Identifiers
Symbol| SOAT1
Alt. symbols| ACAT, SOAT, STAT
NCBI gene| 6646
HGNC| 11177
OMIM| 102642
RefSeq| NM_003101
UniProt| P35610
Other data
EC number| 2.3.1.26
Locus| Chr. 1 q25
sterol O-acyltransferase 2

Identifiers
Symbol| SOAT2
Alt. symbols| ACAT2
NCBI gene| 8435
HGNC| 11178
OMIM| 601311
RefSeq| NM_003578
UniProt| O75908
Other data
EC number| 2.3.1.26
Locus| Chr. 12 [1]

Sterol O-acyltransferase (also called Acyl-CoA cholesterol acyltransferase, Acyl-CoA cholesterin acyltransferase[citation needed] or simply ACAT) is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.

Sterol O-acyltransferase catalyzes the chemical reaction:

acyl-CoA + cholesterol ⇌ CoA + cholesterol ester

Thus, the two substrates of this enzyme are acyl-CoA and cholesterol, whereas its two products are CoA and cholesteryl ester.

This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups, the membrane-bound O-acyltransferases. This enzyme participates in bile acid biosynthesis.

## Contents

* 1 Class and structure
* 2 Mechanism
* 3 Isoforms
* 3.1 SOAT1 (ACAT1)
* 3.2 SOAT2 (ACAT2)
* 4 Yeast
* 5 Plant Synthesis of Steryl Esters
* 6 See also
* 7 References
* 8 Further reading

## Class and structure

Acyl-CoA cholesterol acyl transferase EC 2.3.1.26, more simply referred to as ACAT, also known as sterol O-acyltransferase (SOAT), belongs to the class of enzymes known as acyltransferases. The role of this enzyme is to transfer fatty acyl groups from one molecule to another. ACAT is an important enzyme in bile acid biosynthesis.

In nearly all mammalian cells, ACAT catalyzes the intracellular esterification of cholesterol and formation of cholesteryl esters. The esterification of cholesterol mediated by ACAT is functionally significant for several reasons. ACAT-mediated esterification of cholesterol limits its solubility in the cell membrane lipids and thus promotes accumulation of cholesterol ester in the fat droplets within cytoplasm; this process is important because the toxic accumulation of free cholesterol in various cell membrane fractions is prevented. Most of the cholesterol absorbed during intestinal transport undergoes ACAT-mediated esterification before incorporation in chylomicrons. In the liver, ACAT-mediated esterification of cholesterol is involved in the production and release of apoB-containing lipoproteins. ACAT also plays an important role in foam cell formation and atherosclerosis by participating in accumulating cholesterol esters in macrophages and vascular tissue. The rate-controlling enzyme in cholesterol catabolism, hepatic cholesterol 7-hydroxylase, is believed to be regulated partly by ACAT.[1]

## Mechanism

The mechanism scheme is as follows:
Acyl-CoA + Cholesterol ←→ CoA + Cholesteryl ester[2]

## Isoforms

There are two isoforms of SOAT (also sometimes referred to as ACAT) that have been reported to date: SOAT1 and SOAT2. SOAT1 is characterized by its ubiquitous presence in tissues with the exception of the intestine, where SOAT2 is prevalent. The different isoforms are also associated with different pathologies associated with abnormalities in lipid metabolism.[3]

### SOAT1 (ACAT1)

Previous studies have shown that SOAT modulates proteolytic processing in cell-based and animal models of Alzheimer's disease. A follow-up study reports that SOAT1 RNAi reduced cellular SOAT1 protein and cholesteryl ester levels while causing a slight increase in free cholesterol content of endoplasmic reticulum membranes. The data also showed that a modest decrease in SOAT activity led to suppressive effects on Abeta generation.[3]

### SOAT2 (ACAT2)

In a recent study, it was shown that SOAT2 activity is upregulated as a result of chronic renal failure. This study was specific to hepatic SOAT, which plays a major role in hepatic production and release of very low density lipoprotein (VLDL), release of cholesterol, foam cell formation, and atherogenesis.[3] In another study, non-human primates revealed a positive correlation between liver cholesteryl ester secretion rate and the development of coronal artery atherosclerosis. The results of the experiment are indicative that under all of the conditions of cellular cholesterol availability tested, the relative level of SOAT2 expression affects the cholesteryl ester content, and therefore the atherogenecity of nascent apoB-containing lipoproteins.[4]

## Yeast

In yeast, acyl-CoA:sterol acyltransferase (ASAT) is functionally equivalent to ACAT. Although studies in vitro and in yeast suggest that the acyl-CoA binding protein (ACBP) may modulate long-chain fatty acyl-CoA (LCFA-CoA) distribution, the physiological function in mammals is unresolved. Recent research suggests that ACBP expression may play a role in LCFA-CoA metabolism in a physiological context.[5]

In S. cerevisiae, the accumulation of ergosteryl esters accompanies entry into the stationary phase and sporulation. Researchers have identified two genes in yeast, ARE2 and ARE1, that encode the different isozymes of ASAT. In yeast, Are2 is the major catalytic isoform. Mitotic cell growth and spore germination are not compromised when these genes are deleted, but diploids that are homozygous for an ARE2 null mutation exhibit a decrease in sporulation efficiency.[6]

## Plant Synthesis of Steryl Esters

In plants cellular sterol ester synthesis is performed by an enzyme different from mammalian ACAT and yeast ASAT; it is performed by Phospholipid:Sterol Acyltransferase (PSAT). A recent study shows that PSAT is involved in the regulation of the pool of free sterols and the amount of free sterol intermediates in the membranes. It is also described as the only intracellular enzyme discovered that catalyzes an acyl-CoA independent sterol ester formation. PSAT is therefore considered to have a similar physiological function in plant cells as ACAT in animal cells.[7]

## See also

* ACAT1 mRNA
* Lecithin—cholesterol acyltransferase (LCAT)

## References

1. ↑ "Structure of the human acyl-CoA:cholesterol acyltransferase-2 (ACAT-2) gene and its relation to dyslipidemia". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1531 (3): 230–40. April 2001. doi:10.1016/S1388-1981(01)00106-8. PMID 11325614.
2. ↑ "KEGG Reaction: R01461". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. http://www.genome.jp/dbget-bin/www_bget?reaction+R01461. Retrieved 2009-05-06.
3. ↑ 3.0 3.1 3.2 "ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins". Journal of Lipid Research 48 (7): 1618–27. July 2007. doi:10.1194/jlr.M700109-JLR200. PMID 17438337.
4. ↑ "Knockdown of ACAT-1 Reduces Amyloidogenic Processing of APP". FEBS Letters 581 (8): 1688–92. April 2007. doi:10.1016/j.febslet.2007.03.056. PMID 17412327.
5. ↑ "Acyl-coenzyme A binding protein expression alters liver fatty acyl-coenzyme A metabolism". Biochemistry 44 (30): 10282–97. August 2005. doi:10.1021/bi0477891. PMID 16042405.
6. ↑ "Molecular cloning and characterization of two isoforms of Saccharomyces cerevisiae acyl-CoA:sterol acyltransferase". The Journal of Biological Chemistry 271 (39): 24157–63. September 1996. doi:10.1074/jbc.271.39.24157. PMID 8798656. http://www.jbc.org/cgi/content/full/271/39/24157.
7. ↑ "Cellular sterol ester synthesis in plants is performed by an enzyme (phospholipid:sterol acyltransferase) different from the yeast and mammalian acyl-CoA:sterol acyltransferases". The Journal of Biological Chemistry 280 (41): 34626–34. October 2005. doi:10.1074/jbc.M504459200. PMID 16020547.

## Further reading

* Figure 2 of the esterification reaction with one molecule of free cholesterol, oleic acid, catalyzed by acyl-CoA: cholesterol acyltransferase. It gives the cholesterol ester cholesterol oleate. from Sigrid Hahn; Hans-Ulrich Klör (2001). Knoll Lexikon Adipositas. Aesopus-Verlag. ISBN 978-3-7773-1774-8. https://books.google.com/books?id=N1BAAAAACAAJ. Retrieved 22 June 2013(German) Encyclopedia obesity
* Sgoutas DS (1970). "Effect of geometry and position of ethylenic bond upon acyl coenzyme A--cholesterol-O-acyltransferase". Biochemistry 9 (8): 1826-33. doi:10.1021/bi00810a024. PMID 5439042.
* "Role of acylcoenzyme A: cholesterol o-acyltransferase in cholesterol metabolism". Prog. Lipid Res. 18 (1): 31-53. 1979. doi:10.1016/0163-7827(79)90003-1. PMID 42927.
* "Characterization of sterol-ester synthetase in Saccharomyces cerevisiae". Biochim. Biophys. Acta 575 (1): 148-55. 1979. doi:10.1016/0005-2760(79)90140-1. PMID 389289.

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* e

Transferases: acyltransferases (EC 2.3)

2.3.1: other than amino-acyl groups|

* acetyltransferases: Acetyl-Coenzyme A acetyltransferase
* N-Acetylglutamate synthase
* Choline acetyltransferase
* Dihydrolipoyl transacetylase
* Acetyl-CoA C-acyltransferase
* Beta-galactoside transacetylase
* Chloramphenicol acetyltransferase
* N-acetyltransferase
* Serotonin N-acetyl transferase
* HGSNAT
* ARD1A
* Histone acetyltransferase
* P300/CBP
* NAT2

* palmitoyltransferases: Carnitine O-palmitoyltransferase
* CPT1
* CPT2
* Serine C-palmitoyltransferase
* SPTLC1
* SPTLC2

* other: Acyltransferase like 2
* Aminolevulinic acid synthase
* Beta-ketoacyl-ACP synthase
* Glyceronephosphate O-acyltransferase
* Lecithin—cholesterol acyltransferase

* Glycerol-3-phosphate O-acyltransferase
* 1-acylglycerol-3-phosphate O-acyltransferase
* 2-acylglycerol-3-phosphate O-acyltransferase
* ABHD5

2.3.2: Aminoacyltransferases|

* Gamma-glutamyl transpeptidase
* Peptidyl transferase
* Transglutaminase
* Tissue transglutaminase
* Keratinocyte transglutaminase
* Factor XIII

2.3.3: converted into alkyl on transfer|

* Citrate synthase
* ATP citrate lyase
* HMG-CoA synthase
* Malate synthase

* v
* t
* e

Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

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