Information on EC 2.3.1.26 - sterol O-acyltransferase

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY
2.3.1.26
-
RECOMMENDED NAME
GeneOntology No.
sterol O-acyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acyl-CoA + cholesterol = CoA + cholesterol ester
show the reaction diagram
mechanism, a histidine is implicated in the catalytic mechanism of the enzyme
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Steroid biosynthesis
-
-
sterol:steryl ester interconversion (yeast)
-
-
SYSTEMATIC NAME
IUBMB Comments
acyl-CoA:cholesterol O-acyltransferase
The animal enzyme is highly specific for transfer of acyl groups with a single cis double bond that is nine carbon atoms distant from the carboxy group.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ACAT
-
-
-
-
acyl coenzyme A-cholesterol-O-acyltransferase
-
-
-
-
acyl-CoA:cholesterol acyltransferase
-
-
-
-
acylcoenzyme A:cholesterol O-acyltransferase
-
-
-
-
acyltransferase, cholesterol
-
-
-
-
cholesterol acyltransferase
-
-
-
-
cholesterol ester synthase
-
-
-
-
cholesterol ester synthetase
-
-
-
-
cholesteryl ester synthetase
-
-
-
-
sterol-ester synthase
-
-
-
-
sterol-ester synthetase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9027-63-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ACAT1 expressed by CHO cells; ACAT2 expressed by CHO cells
-
-
Manually annotated by BRENDA team
African green monkey
-
-
Manually annotated by BRENDA team
recombinant isoforms ACAT1 and ACAT2
-
-
Manually annotated by BRENDA team
African green monkey
-
-
Manually annotated by BRENDA team
expression in chinese hamster ovary cells, isoform ACAT2
-
-
Manually annotated by BRENDA team
isoform ACAT1
-
-
Manually annotated by BRENDA team
isoforms ACTA1 and ACAT2, overexpression in rat hepatoma McA-RH7777 cells
-
-
Manually annotated by BRENDA team
recombinant isoforms ACAT1 and ACAT2 with His-tag each
-
-
Manually annotated by BRENDA team
transforming growth factor-beta1 increases enzyme expression 2fold with an increase in activity of 1.8fold during differentiation of monocytes to macrophages. Addition of transforming growth factor-beta1 after differentiation does not alter enzyme expression
-
-
Manually annotated by BRENDA team
male, F1B hybrid, fed with a modified version of the NIH-07 open formula, cereal-based rodent diet enriched with one out of 4 dietary fatty acids
-
-
Manually annotated by BRENDA team
Syrian hamster
-
-
Manually annotated by BRENDA team
inbred strains with high/low response in low-density lipoprotein cholesterol to dietary cholesterol and fat, resp.
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
C57B1/6
-
-
Manually annotated by BRENDA team
isoform ACAT1
UniProt
Manually annotated by BRENDA team
isoform ACAT2
UniProt
Manually annotated by BRENDA team
Mus musculus C57B1/6
C57B1/6
-
-
Manually annotated by BRENDA team
male Sprague-Dawley strain
-
-
Manually annotated by BRENDA team
male wistar rat
-
-
Manually annotated by BRENDA team
male Wistar strain
-
-
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
male Sprague-Dawley strain
-
-
Manually annotated by BRENDA team
Rattus norvegicus male Wistar
male Wistar strain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mice lacking ACAT1 or ACAT2 do not have a decreased PREG ester contents in adrenals, nor do they have altered levels of the three major secreted adrenal steroids in serum, mice lacking ACAT1 or ACAT2 do not have a decreased pregnenolone ester contents in adrenals, nor do they have altered levels of the three major secreted adrenal steroids in serum
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + cholesterol
CoA + cholesteryl acetate
show the reaction diagram
-
16% of the activity with oleoyl-CoA
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
esterification of 3beta-hydroxy group
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
acyl-CoA derivatives can be replaced by ATP, Mg2+, CoA and fatty acids, in-situ production of acyl-CoA
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
acyl-CoA derivatives can be replaced by ATP, Mg2+, CoA and fatty acids, in-situ production of acyl-CoA
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
the animal enzyme is highly specific for transfer of acyl groups with a single cis-double-bond 9 carbon atoms distant from the carboxyl group
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
ACAT-1 plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
Rattus norvegicus male Wistar
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
Rattus norvegicus male Sprague-Dawley
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
Rattus norvegicus male Sprague-Dawley
-
-
-
?
docosahexaenoyl-CoA + cholesterol
CoA + cholesteryl docosahexanoate
show the reaction diagram
-
rate of cholesteryl ester formation is faster and more cholesteryl ester is formed with oleic acid compared to docosahexanoic acid. Docosahexanoic acid substantially reduces cholesteryl ester formation when given in combination with oleic acid
-
-
?
elaidoyl-CoA + cholesterol
CoA + cholesteryl elaidate
show the reaction diagram
-
-
-
?
lauroyl-CoA + cholesterol
CoA + cholesteryl laurate
show the reaction diagram
-
62% of the activity with oleoyl-CoA
-
?
linelaidoyl-CoA + cholesterol
CoA + cholesteryl linelaidate
show the reaction diagram
-
-
-
?
linoleoyl-CoA + cholesterol
CoA + cholesteryl linoleate
show the reaction diagram
-
-
-
?
linoleoyl-CoA + cholesterol
CoA + cholesteryl linoleate
show the reaction diagram
-
-
-
?
linoleoyl-CoA + cholesterol
CoA + cholesteryl linoleate
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
may play an important role in regulation of the accumulation of cholesterol esters within smooth muscle cells of the artery wall during atherogenesis and in synthesis of cholesterol esters during hepatic very low-density lipoprotein synthesis and secretion
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
role in lipoprotein metabolism and atherogenesis
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
the enzyme is relevant for cellular cholesterol esterification in vivo, the regulation in human mononuclear phagocytes indicates that the enzyme is also involved in foam cell formation during early atherogenesis
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
the high activity of intestinal enzyme renders it possible that the enzyme plays a role in cholesterol absorption
-
?
myristoyl-CoA + cholesterol
CoA + cholesteryl myristate
show the reaction diagram
-
37% of the activity with oleoyl-CoA
-
?
oleoyl-CoA + 4alpha-methylcholest-7-en-3beta-ol
CoA + 4alpha-methylcholest-7-en 3-oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + 4alpha-methylcholest-7-en-3beta-ol
CoA + 4alpha-methylcholest-7-en 3-oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + 4alpha-methylcholest-7-en-3beta-ol
CoA + oleate ester of 4alpha-methylcholest-7-en-3beta-ol
show the reaction diagram
-
-
-
?
oleoyl-CoA + 5alpha,6alpha-epoxycholesterol
CoA + 5alpha,6alpha-epoxycholesteryl oleate
show the reaction diagram
-
activity comparable to cholesterol
-
-
?
oleoyl-CoA + 5alpha-cholest-8(14)-en-3beta-ol-15-one
CoA + cholestanyl oleate
show the reaction diagram
Rattus norvegicus, Rattus norvegicus male Sprague-Dawley
-
-
-
?
oleoyl-CoA + 5alpha-cholest-8(14)-en-3beta-ol-15-one
CoA + oleate ester of 5alpha-cholest-8(14)-en-3beta-ol-15-one
show the reaction diagram
Rattus norvegicus, Rattus norvegicus male Sprague-Dawley
-
-
-
?
oleoyl-CoA + 7alpha-hydroxycholesterol
CoA + 7alpha-hydroxycholesteryl oleate
show the reaction diagram
-
activity comparable to cholesterol
-
-
?
oleoyl-CoA + campesterol
CoA + campesteryl oleate
show the reaction diagram
-
campesterol is a poor substrate
-
?
oleoyl-CoA + campesterol
CoA + campesteryl oleate
show the reaction diagram
-
20% of the activity with cholesterol
-
?
oleoyl-CoA + cholest-4-en-3beta-ol
CoA + cholest-4-en 3-oleate
show the reaction diagram
-
low activity
-
?
oleoyl-CoA + cholest-4-en-3beta-ol
CoA + cholest-4-en 3-oleate
show the reaction diagram
-
low activity
-
?
oleoyl-CoA + cholestanol
CoA + cholestanyl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholestanol
CoA + cholestanyl oleate
show the reaction diagram
-
cholestanol is esterified by the enzyme at almost the same rate as cholesterol
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
Q61263
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
P53629
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
O75908
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
-
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
highest activity
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
recombinant enzyme
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
the dimeric enzyme responds to cholesterol in essentially the same manner as the tetrameric enzyme
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
rate of cholesteryl ester formation is faster and more cholesteryl ester is formed with oleic acid compared to docosahexanoic acid. Docosahexanoic acid substantially reduces cholesteryl ester formation when given in combination with oleic acid
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
-
intrinsic fluorescence spectroscopy is used to study the binding between the enzyme and its substrates in CHAPS/phospholipid mixed micelles. Results show that oleoyl-CoA binds to ACAT1 with Kd=1.9 M and elicits significant structural changes of the protein as manifested by the significantly positive changes in its fluorescence spectrum
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
Rattus norvegicus male Wistar
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
Rattus norvegicus male Wistar
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
Rattus norvegicus male Sprague-Dawley
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesteryl oleate
show the reaction diagram
Rattus norvegicus male Sprague-Dawley
-
-
-
?
oleoyl-CoA + cholesterol
CoA + cholesterol oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
oleoyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
oleoyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
oleoyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
oleoyl-CoA + cholesterol
?
show the reaction diagram
-
ACAT activity assay
-
-
?
oleoyl-CoA + desmosterol
CoA + desmosteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + desmosterol
CoA + desmosteryl oleate
show the reaction diagram
-
62% of the activity with cholesterol
-
?
oleoyl-CoA + episterol
CoA + episteryl oleate
show the reaction diagram
-
62% of the activity with cholesterol
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
P53629
endogenous ergosterol as substrate or exogenous ergosterol in the form of ergosterol/phosphatidylcholine vesicles as substrate
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
-
recombinant enzyme: restores ergosteryl oleate formation in vivo to only approximately 8% of that catalysed by yeast enzyme in wild-type cells
-
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
-
147% of the activity with cholesterol
-
?
oleoyl-CoA + ergosterol
CoA + ergosteryl oleate
show the reaction diagram
-
53% of the activity with cholesterol
-
-
?
oleoyl-CoA + fecosterol
CoA + fecosteryl oleate
show the reaction diagram
-
48% of the activity with cholesterol
-
?
oleoyl-CoA + lanosterol
CoA + lanosteryl oleate
show the reaction diagram
-
65% of the activity with cholesterol
-
?
oleoyl-CoA + lathosterol
CoA + lathosteryl oleate
show the reaction diagram
-
-
-
?
oleoyl-CoA + lathosterol
CoA + lathosteryl oleate
show the reaction diagram
-
41% of the activity with cholesterol
-
?
oleoyl-CoA + sitosterol
CoA + cholesteryl oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + sitosterol
CoA + sitosterol oleate
show the reaction diagram
-
-
-
-
?
oleoyl-CoA + zymosterol
CoA + zymosteryl oleate
show the reaction diagram
-
93% of the activity with cholesterol
-
?
oleyl-CoA + cholesterol
?
show the reaction diagram
-
-
-
-
-
oleyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
oleyl-CoA + cholesterol
?
show the reaction diagram
-
activity assay
-
-
?
palmitoleoyl-CoA + cholesterol
CoA + cholesteryl palmitoleate
show the reaction diagram
-
91% of the activity with oleoyl-CoA
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
approximately 50% of the activity with oleoyl-CoA
-
?
palmitoyl-CoA + cholesterol
CoA + cholesteryl palmitate
show the reaction diagram
-
47% of the activity with oleoyl-CoA
-
?
pregnenolone + oleyl CoA
?
show the reaction diagram
-
without cholesterol, pregnenolone is a poor ACAT substrate, with cholesterol, the Vmax for PREG esterification increases by 100fold, without cholesterol, pregnenolone is a poor ACAT substrate, with cholesterol, the Vmax for pregnenolone esterification increases by 100fold
-
-
?
stearoyl-CoA + cholesterol
CoA + cholesteryl stearate
show the reaction diagram
-
-
-
-
?
stearoyl-CoA + cholesterol
CoA + cholesteryl stearate
show the reaction diagram
-
-
-
?
stearoyl-CoA + cholesterol
CoA + cholesteryl stearate
show the reaction diagram
-
-
-
?
stearyl-CoA + cholesterol
CoA + cholesteryl stearate
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
Rattus norvegicus, Rattus norvegicus male Sprague-Dawley
-
the enzyme plays an important role in maintenance of hepatic cholesterol homeostasis
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
oleic acid is not incorporated into cholesterol esters by placental microsomes even in the presence of ATP, CoA and MgCl2
-
-
-
additional information
?
-
-
structural requirements of sterol substrate
-
-
-
additional information
?
-
-
enzyme activity is regulated by the acyl-CoA binding protein ACBP
-
-
-
additional information
?
-
-
the enzyme has a broad substrate specificity for sterols and acyl-CoAs
-
-
-
additional information
?
-
-
campesterol is a poor substrate, indicating the alkyl side chain plays an important role in the enzyme reaction
-
-
-
additional information
?
-
-
maximal ester formation is obtained when the longest chain on C-20 has five carbons and either an increase or decrease in the number of carbons reduce the amount of ester formed
-
-
-
additional information
?
-
-
a part of the substrate selectivity may be due to the presence of acyl-CoA hydrolase in the microsomal preparations. For this enzyme, the preferred substrate is palmitoyl-CoA which is hydrolysed about 8times faster than oleoyl-CoA, investigations into the sterol specificity of the enzyme
-
-
-
additional information
?
-
-
sitosterol, stigmasterol, ergosterol, lanosterol, cycloartenol are not substrates
-
-
-
additional information
?
-
-
3-epicholesterol is not a substrate, indicating a requirement for a 3beta-hydroxyl group
-
-
-
additional information
?
-
-
two closely related enzymes identified that catalyse the esterification of cholesterol using acyl-CoA substrates, namely ACAT1 and ACAT2, the orientation of ACAT2 in the endoplasmic reticulum membrane, in addition to its expression only in liver and intestine, suggests that this enzyme may have as a primary function, the secretion of cholesteryl esters into apolipoprotein B-containing lipoproteins
-
-
-
additional information
?
-
-
isoform ACAT2 displays significantly greater selectivity for cholesterol compared with sitosterol than ACAT1
-
-
-
additional information
?
-
-
stereochemistry of 3-hydroxyl group at steroid ring is a critical structural feature for ACAT1 isoform
-
-
-
additional information
?
-
-
very poor substrates: 7-ketocholesterol, 7beta-hydroxycholesterol, 5beta,6beta-epoxycholesterol, 24(S),25-epoxycholesterol
-
-
-
additional information
?
-
O88908
hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins
-
-
-
additional information
?
-
-
ACAT2 plays an important role in intestinal cholesterol absorption
-
-
-
additional information
?
-
Rattus norvegicus male Sprague-Dawley
-
structural requirements of sterol substrate, campesterol is a poor substrate, indicating the alkyl side chain plays an important role in the enzyme reaction, maximal ester formation is obtained when the longest chain on C-20 has five carbons and either an increase or decrease in the number of carbons reduce the amount of ester formed, sitosterol, stigmasterol, ergosterol, lanosterol, cycloartenol are not substrates, 3-epicholesterol is not a substrate, indicating a requirement for a 3beta-hydroxyl group
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
-
?
acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
ACAT-1 plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
-
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
may play an important role in regulation of the accumulation of cholesterol esters within smooth muscle cells of the artery wall during atherogenesis and in synthesis of cholesterol esters during hepatic very low-density lipoprotein synthesis and secretion
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
responsible for cellular synthesis of cholesterol esters in various cell types
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
role in lipoprotein metabolism and atherogenesis
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
the enzyme is relevant for cellular cholesterol esterification in vivo, the regulation in human mononuclear phagocytes indicates that the enzyme is also involved in foam cell formation during early atherogenesis
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
-
the high activity of intestinal enzyme renders it possible that the enzyme plays a role in cholesterol absorption
-
?
long-chain fatty acyl-CoA + cholesterol
CoA + cholesterol ester
show the reaction diagram
Rattus norvegicus, Rattus norvegicus male Sprague-Dawley
-
the enzyme plays an important role in maintenance of hepatic cholesterol homeostasis
-
?
additional information
?
-
-
two closely related enzymes identified that catalyse the esterification of cholesterol using acyl-CoA substrates, namely ACAT1 and ACAT2, the orientation of ACAT2 in the endoplasmic reticulum membrane, in addition to its expression only in liver and intestine, suggests that this enzyme may have as a primary function, the secretion of cholesteryl esters into apolipoprotein B-containing lipoproteins
-
-
-
additional information
?
-
O88908
hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CoA
-
required by the in-situ acyl-CoA production
CoA
-
required by the in-situ acyl-CoA production
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
stimulates
Mg2+
-
required for the acylation of free cholesterol
Mg2+
-
stimulates
Mg2+
-
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl (9Z,12E)-octadeca-9,12-dienoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-methylbutanoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl benzoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl butanoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pent-4-enoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pentanoate
-
-
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl propanoate
-
-
(1R,3R,7R)-1-[(1S)-1-hydroxypropyl]-3,7-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]heptan-5-one
-
45% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(1R,3R,7S)-1-[(1S)-1-hydroxypropyl]-3,7-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]heptan-5-one
-
66% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(1R,3R,7S)-1-[(1S)-1-hydroxypropyl]-3,7-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]heptan-5-one
-
0.01 mM, 66% inhibition
(1S)-1-[(1R,3R,5R)-3,5-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]hept-1-yl]propan-1-ol
-
0.01 mM, 45% inhibition
(24R)-ethylcholest-5-ene-3,7-diol
-
-
(3R,5R,7R,8S)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1S)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
0.01 mM, 23% inhibition
(3R,5S,7S,8R)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1R)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
27% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-6-(pentanoyloxy)-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-3-yl benzoate
-
; selective for isoform ACAT2
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl dipentanoate
-
; selective for isoform ACAT2
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl 3-methylbutanoate
-
; selective for isoform ACAT2
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate
-
; i.e. pyripyropene A,selective for isoform ACAT2
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-3-(butanoyloxy)-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl hexanoate
-
; selective for isoform ACAT2
(3S,4S)-3-[(1R,2R)-2-azido-1-hydroxybutyl]-3-bromo-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
65% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(3S,4S)-3-[(1S,2S)-2-azido-1-hydroxybutyl]-3-bromo-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
60% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(3S,4S,4aR,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-4,12,12b-trihydroxy-6a-methyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl (2E)-pent-2-enoate
-
; selective for isoform ACAT2
(3S,5R,7R,8S)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1S)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
0.01 mM, 27% inhibition
(3S,5S,7S,8R)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1R)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
23% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(1-methylethyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
; selective for isoform ACAT2
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(2-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
; selective for isoform ACAT2
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(4-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
; selective for isoform ACAT2
(4S)-3-[(1R,2S)-2-azido-1-hydroxybutyl]-3-[(R)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
0.01 mM, 87% inhibition
(4S)-3-[(1R,2S)-2-azido-1-hydroxybutyl]-3-[(S)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
87% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(4S)-3-[(1S,2R)-2-azido-1-hydroxybutyl]-3-[(R)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
79% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
(4S)-3-[(1S,2R)-2-azido-1-hydroxybutyl]-3-[(S)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
0.01 mM, 79% inhibition
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid
-
-
(6R,9S,13S)-3-benzyl-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
inhibition of both isoforms ACAT1 and ACAT2; inhibition of both isoforms ACAT1 and ACAT2
(6S,9S,13R)-9-(2-chlorobenzyl)-6-methyl-3-[(1S)-1-methylpropyl]-13-pentyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT1
(6S,9S,13S)-6-methyl-13-[(1S)-1-methylnonyl]-3-[(1S)-1-methylpropyl]-9-(naphthalen-2-ylmethyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT2
(6S,9S,13S)-6-methyl-9-(4-methylbenzyl)-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT1
(6S,9S,13S)-9-(3-chlorobenzyl)-6-methyl-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT1
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1R)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT2
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
; selective inhibition of isoform ACAT2
(S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-alpha-phenylacetanilide
-
i.e. F12511, may have direct antiatherosclerotic effects on the cells of the vascular wall
(S)-7-dimethylamino-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-isobutyryl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
-
shows about 16fold stronger anti-foam cell formation activity, 3fold stronger hepatic ACAT inhibitory activity, similar anti-low density lipoprotein (LDL) oxidative activity and 2fold more potent protective activity against macrophage cell death by oxidative stress in comparison with Pactimibe
(S)-N-(2,6-diisopropylphenyl)-2-octanoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
-
ratio IC50 of pactimibe/IC50 of test compound: 2.2
-
(S)-N-(4-amino-2,6-diisopropylphenyl)-2-octanoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride
-
ratio IC50 of pactimibe/IC50 of test compound: 0.96
-
(S)-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-octanoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
-
ratio IC50 of pactimibe/IC50 of test compound: 10
-
(Z)-17(20)-dehydrocholesterol
-
inhibits esterification of endogenous cholesterol
1-(2,6-diisopropyl-phenyl)-3-[4-(4'-nitrophenylthio)phenyl] urea
-
VULM 1457
1-(3,6-dimethylpyrazin-2-yl)-4-(5-phenylpyridazin-3-yl)-1,4-diazepane
-
0.1 mg/ml, 62% inhibition
1-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]-3-{4-[(ethylamino)methyl]-2,6-bis(1-methylethyl)phenyl}urea
-
IC50: 680 nM
1-[2,4-bis(1-methylethyl)pyridin-3-yl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]urea
-
IC50: 5.4 nM
1-[3-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 43 nM
1-[4-(aminomethyl)-2,6-bis(1-methylethyl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]urea
-
IC50: 382 nM
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-(1-butyl-4-{3-[3-(ethylamino)propoxy]phenyl}-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl)urea
-
IC50: 452 nM
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-2-oxo-4-[3-(3-piperidin-1-ylpropoxy)phenyl]-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 540 nM
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-2-oxo-4-[3-(3-pyrrolidin-1-ylpropoxy)phenyl]-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 427 nM
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
i.e. SMP-797, possessing a potent ACAT inhibitory activity and significantly enhanced aqueous solubility under acidic conditions. The compound is a promising agent for oral treatment of hypercholesterolemia.IC50: 21 nM
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(4-hydroxybutoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 61 nM
1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-({1-[2-(3-hydroxypropoxy)phenyl]-4-(3-methoxyphenyl)piperidin-4-yl}methyl)urea
-
-
1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-{[1-(2-butoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl}urea
-
poor solubility
1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-{[1-(2-butoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl}urea
-
-
17alpha-hydroxyprogesterone
-
-
2,3,6,8-tetramethoxy-5-(piperidin-1-ylsulfonyl)-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 10.53% inhibition
2,3,6,8-tetramethoxy-5-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)sulfonyl]-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 51.34% inhibition
2,3,6,8-tetramethoxy-5-{[4-(3-methylphenyl)piperazin-1-yl]sulfonyl}-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 64.8% inhibition
2,3,6,8-tetramethoxy-5-{[4-(4-methoxyphenyl)piperazin-1-yl]sulfonyl}-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 36.92% inhibition
2,3,6,8-tetramethoxy-5-{[4-(pyridin-2-yl)piperazin-1-yl]sulfonyl}-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 43.56% inhibition
2,3,6,8-tetramethoxy-9-oxo-N-(2-phenylpropyl)-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 10.78% inhibition
2,3,6,8-tetramethoxy-N-(naphthalen-2-ylmethyl)-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 25% inhibition
2-[(2E,6Z,8E,10E)-dodeca-2,6,8,10-tetraenoylamino]-1,1-dimethylethyl acetate
-
IC50: 0.0281 mM; IC50: 0.0875 mM
2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
-
K-604
20-Methylcholesterol
-
inhibits esterification of endogenous cholesterol
20alpha-hydroxypregn-4-en-3-one
-
-
2alpha,3beta,23-trihydroxyolean-12-en-28-oic acid
-
arjunolic acid, at 0.1 mg/ml, 60.8% inhibition of isoform ACAT1, 5.3% inhibition of isoform ACAT2
2alpha,3beta-dihydroxyolean-12-en-28-oic acid
-
maslinic acid, at 0.1 mg/ml, 46.2% inhibition of isoform ACAT1, 17.3% inhibition of isoform ACAT2
-
2alpha,3beta-dihydroxyurs-12-en-28-oic acid
-
corosolic acid, at 0.1 mg/ml, 46.7% inhibition of isoform ACAT1, 3% inhibition of isoform ACAT2
-
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(5-phenylpyridazin-3-yl)amino]pentyl]urea
-
0.05 mg/ml, 46% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(5-phenylpyridazin-3-yl)sulfanyl]pentyl]urea
-
0.05 mg/ml, 75% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(5-phenylpyridazin-3-yl)sulfinyl]pentyl]urea
-
0.05 mg/ml, 62% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(5-phenylpyridazin-3-yl)sulfonyl]pentyl]urea
-
0.05 mg/ml, 67% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(6-phenylpyridazin-3-yl)amino]pentyl]urea
-
0.05 mg/ml, 89% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(6-phenylpyridazin-3-yl)sulfinyl]pentyl]urea
-
0.05 mg/ml, 55% inhibition
3-(2,4-difluorophenyl)-1-heptyl-1-[5-[(6-phenylpyridazin-3-yl)sulfonyl]pentyl]urea
-
0.05 mg/ml, 43% inhibition
3-(2,4-difluorophenyl)-1-octyl-1-[5-[(6-phenylpyridazin-3-yl)sulfanyl]pentyl]urea
-
0.05 mg/ml, 44% inhibition
3-(2,4-difluorophenyl)-1-[5-[(5,6-diphenylpyridazin-3-yl)amino]pentyl]-1-heptylurea
-
0.05 mg/ml, 87% inhibition
3-(2,4-difluorophenyl)-1-[5-[(5,6-diphenylpyridazin-3-yl)sulfanyl]pentyl]-1-heptylurea
-
0.05 mg/ml, 75% inhibition
3-(2,4-difluorophenyl)-1-[5-[(5,6-diphenylpyridazin-3-yl)sulfinyl]pentyl]-1-heptylurea
-
0.05 mg/ml, 65% inhibition
3-(2,4-difluorophenyl)-1-[5-[(5,6-diphenylpyridazin-3-yl)sulfonyl]pentyl]-1-heptylurea
-
0.05 mg/ml, 70% inhibition
3-[4-(3,6-dimethylpyrazin-2-yl)piperazin-1-yl]-5-phenylpyridazine
-
0.1 mg/ml, 57% inhibition
3beta,23-dihydroxyurs-12-en-28-oic acid
-
23-hydroxyursolic acid, at 0.1 mg/ml, 41.5% inhibition of isoform ACAT1, 22.2% inhibition of isoform ACAT2
3beta-hydroxylup-20(29)-en-28-oic acid
-
-
3beta-hydroxyolean-12-en-28-oic acid
-
oleanoic acid, at 0.1 mg/ml, 22.6% inhibition of isoform ACAT1, 10.2% inhibition of isoform ACAT2
3beta-hydroxyurs-12-en-28-al
-
ursolic aldehyde, at 0.1 mg/ml, 21.8% inhibition of isoform ACAT1, 13% inhibition of isoform ACAT2
3beta-hydroxyurs-12-en-28-oic acid
-
ursolic acid, at 0.1 mg/ml, 23.1% inhibition of isoform ACAT1, 16.7% inhibition of isoform ACAT2
5,5'-dibutoxy-2,2'-bifuran
-
-
5,5'-dithiobis-(2-nitrobenzoate)
-
50% inhibition of ACAT1 at 0.01 mM
5-(1-butoxy-2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}propyl)-1,3-benzodioxole
-
0.125 mM, 28% inhibition; IC50: 0.017 mM
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-ethoxypropyl)-1,3-benzodioxole
-
0.125 mM, 29% inhibition; IC50: 0.031 mM
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-methoxypropyl)-1,3-benzodioxole
-
0.125 mM, 45% inhibition; IC50: 0.035 mM
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-propoxypropyl)-1,3-benzodioxole
-
0.125 mM, 33% inhibition; IC50: 0.014 mM
5-[(4-aminopiperazin-1-yl)sulfonyl]-2,3,6,8-tetramethoxy-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 14.5% inhibition
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(heptyloxy)propyl]-1,3-benzodioxole
-
0.125 mM, 26% inhibition; IC50: 0.05 mM
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(hexyloxy)propyl]-1,3-benzodioxole
-
0.125 mM, 33% inhibition; IC50: 0.034 mM
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(nonyloxy)propyl]-1,3-benzodioxole
-
0.125 mM, 10% inhibition; 0.125 mM, 25% inhibition
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(octyloxy)propyl]-1,3-benzodioxole
-
0.125 mM: 19% inhibition; 0.125 mM: 44% inhibition
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(pentyloxy)propyl]-1,3-benzodioxole
-
0.125 mM, 33% inhibition; IC50: 0.02 mM
5-{[(2R,6S)-2,6-dimethylmorpholin-4-yl]sulfonyl}-2,3,6,8-tetramethoxy-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 8.84% inhibition
5-{[3-(dimethylamino)pyrrolidin-1-yl]sulfonyl}-2,3,6,8-tetramethoxy-1,4-dihydro-9H-xanthen-9-one
-
10 microgram/ml, 20.96% inhibition
-
5alpha,8alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3beta-ol
-
-
5alpha-Cholest-8(14)-en-3beta-ol-15-one
-
inhibits the esterification of cholesterol
5alpha-dihydroprogesterone
-
inhibits esterification of endogenous cholesterol
5alpha-dihydroprogesterone
-
-
Acetic anhydride
-
2 distinct tissue types with difference in reactivity, the inhibitor appears to modify a histidine residue
acetone
-
about 40% inhibition at a final concentration of 1% v/v
acetone
-
30-50% inhibition at a final concentration of 1% v/v, inhibition prevented by the addition of cholesterol to the solvent
acetylshikonin
-
-
acyl-CoA binding protein
-
3fold decrease in activity
-
acyl-CoA binding protein/oleoyl-CoA complexes
-
strongly inhibit
-
ADP
-
inactivates
AM-251
-
selective antagonist of cannobinoid receptor CB1. Additionally, reatment of cells reduces cholesteryl ester synthesis in unstimulated and acetylated low densitixy lipoprotein-stimulated Raw 264.7 macrophages, CB2 +/+ and CB2-/- peritoneal macrophages, as well as in vitro, in mouse liver microsomes. Consistent with inhibition of ACAT, the development of foam cell characteristics in macrophages by treatment with acetylated low density lipoprotein is reduced
androstenedione
-
-
androsterone
-
inhibits esterification of endogenous cholesterol
ATP
-
inactivates
aurasperone A
-
isolation from the culture broth of Aspergillus species; isolation from the culture broth of Aspergillus species
aurasperone D
-
isolation from the culture broth of Aspergillus species; isolation from the culture broth of Aspergillus species
averufanin
-
isolation from the culture broth of Aspergillus species; isolation from the culture broth of Aspergillus species
beauvericin
-
IC50: 0.00035 mM, ACAT1; IC50: 0.00035 mM, ACAT2
beauveriolide I
-
IC50: 0.0019 mM, ACAT2; IC50: 0.0022 mM, ACAT1
beauveriolide I
-
-
beauveriolide III
-
IC50: 0.003 mM, ACAT1; IC50: 0.003 mM, ACAT2
beauveriolide III
-
-
beta-hydroxyisovalerylshikonin
-
-
beta-sanshool
-
extracted from Zanthoxylum piperitum DC; IC50: 0.012 mM; IC50: 0.039 mM
beta-sanshool acetate
-
semi-synthetic compound
betulin
-
; IC50: 0.083 mM, hACAT-1
Bovine serum albumin
-
inhibits at high concentrations
-
Bovine serum albumin
-
inhibits at high concentrations
-
butanol
-
about 40% inhibition at a final concentration of 1% v/v
butanol
-
30-50% inhibition at a final concentration of 1% v/v, inhibition prevented by the addition of cholesterol to the solvent
CI-1011
-
-
CI-976
-
inhibits
CI-976
-
cell-free extract of sat1 and sat2 cells: more than 95% inhibition at 0.2 mM, intact sat1 and sat2 cells: approximately 75-80% inhibition at 0.2 mM
CI-976
P53629
cell-free extract of wild-type cells: approximately 90% inhibition at 0.1 mM and more than 95% inhibition at 0.2 mM, intact wild-type cells: approximately 75-80% inhibition at 0.2 mM
CI-976
-
50% inhibition at 0.0116 mM
CL-283,546
-
IC50: 0.00006 mM, ACAT2; IC50: 0.00012 mM, ACAT1
CL-283,546
-
-
CP113818
-
recombinant enzyme, 80-90% inhibition at 0.0002 mM
Cycloartenol
-
inhibits esterification of exogenous cholesterol
dehydroisoandrosterone
-
-
dehydropipernonaline
-
-
dehydroretrofractamide
-
-
deoxycorticosterone
-
inhibits esterification of endogenous cholesterol
deoxycorticosterone
-
-
deoxycorticosterone
-
-
Detergents
-
-
Detergents
-
above their critical micelle concentration, e.g. cholate, deoxycholate, cetyltriethylammonium bromide, Triton X-100, Tween 20, Tween 80, Nonidet P40
diazepam
-
competes with oleoyl-CoA for its binding to microsomal membranes
diethyl dicarbonate
-
2 distinct tissue types with difference in reactivity, DEP-sensitive subtype typified by aortic ACTAT, DEP-resistant subtype typified by liver ACAT, irreversible inhibition, the inhibitor appear to modify a histidine residue
DuP 128
-
inhibits
DuP 128
-
-
DuP 128
P53629
approximately 50% inhibition at 0.03-0.04 mM
DuP 128
-
50% inhibition at 0.00013 mM for HisACAT1, 50% inhibition at 0.0001 mM for the mutants HisACAT1/p64 and HisACAT1/1-65
ergosterol
-
inhibits esterification of exogenous cholesterol
esculeogenin A
-
-
esculeoside A
-
-
estradiol-17beta
-
-
ethanol
-
about 40% inhibition at a final concentration of 1% v/v
ethanol
-
30-50% inhibition at a final concentration of 1% v/v, inhibition prevented by the addition of cholesterol to the solvent
ethyl 1-[(2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthen-5-yl)sulfonyl]piperidine-3-carboxylate
-
10 microgram/ml, 7.99% inhibition
ethyl N-methyl-N-[(2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthen-5-yl)sulfonyl]glycinate
-
10 microgram/ml, 16.79% inhibition
F12511
-
;
-
flavasperone
-
isolation from the culture broth of Aspergillus species, selective for isoform ACAT2
gamma-sanshool
-
extracted from Zanthoxylum piperitum DC; IC50: 0.0797 mM; IC50: 0.0826 mM
GERI-BP001M
-
0.1 mg/ml, 82% inhibition
GERIBP001M
-
0.05 mM, 83% inhibition
glisoprenin A
-
IC50: 0.0004 mM, ACAT1; IC50: 0.0013 mM, ACAT2
HWY-289
-
50% inhibition at 0.0132 mM
hydroxy-beta-sanshool
-
low inhibition; low inhibition
Inhibitor from rabbit liver
-
fatty acid ester, mostly stearate, of a pentacyclic triterpene acid, irreversible inhibition, which is prevented by incubation with bovine serum albumin, half-maximal inhibition occurs at an inhibitor concentration of 0.02 mM
-
isobutyrylshikonin
-
-
K-604
Q61263, Q88908
selective for isoform ACAT-1, use to measure the individual enzymatic activities of isoforms ACAT-1 and ACAT-2; selective for isoform ACAT-1, use to measure the individual enzymatic activities of isoforms ACAT-1 and ACAT-2
K97-0239A
-
IC50: 0.038 mM, ACAT2; IC50: 0.04 mM, ACAT1
K97-0239B
-
IC50: above 0.07 mM, ACAT1; IC50: above 0.7 mM, ACAT2
lanosterol
-
inhibits esterification of exogenous cholesterol
lupeol
-
; IC50: 0.048 mM, hACAT-1
manassantin B
Q61263, Q88908
inhibition of both isoforms ACAT-1 and ACAT-2; inhibition of both isoforms ACAT-1 and ACAT-2
methyl N-[(2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthen-5-yl)sulfonyl]glycinate
-
10 microgram/ml, 5.13% inhibition
MgATP2-
-
inhibition of activity
N'-(3,6-dimethylpyrazin-2-yl)-N,N-diheptylbutane-1,4-diamine
-
0.1 mg/ml, 55% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N,N-diheptylpentane-1,5-diamine
-
0.1 mg/ml, 58% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N,N-diheptylpropane-1,3-diamine
-
0.1 mg/ml, 52% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)butane-1,4-diamine
-
0.1 mg/ml, 87% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)heptane-1,7-diamine
-
0.1 mg/ml, 58% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 79% inhibition; 0.1 mg/ml, 95% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)octane-1,8-diamine
-
0.1 mg/ml, 76% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)pentane-1,5-diamine
-
0.1 mg/ml, 79% inhibition
N'-(3,6-dimethylpyrazin-2-yl)-N-heptyl-N-(5-phenylpyridazin-3-yl)propane-1,3-diamine
-
0.1 mg/ml, 70% inhibition
N,N-diethyl-1-[(2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthen-5-yl)sulfonyl]piperidine-3-carboxamide
-
10 microgram/ml, 12.59% inhibition
N-(3,6-dimethylpyrazin-2-yl)-N'-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 89% inhibition
N-(3-chlorobenzyl)-2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 15.76% inhibition
N-(4,6-dimethyl-1-pentylindolin-7-yl)-2,2-dimethylpropanamide
-
KY-455, an anti-oxidative ACAT inhibitor
N-(4-amino-2, 6-diisopropylphenyl)-N'-[1-butyl-4-[3-(3-hydroxypropoxy) phenyl]-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] urea hydrochloride monohydrate
-
SMP-797
N-(4-fluorobenzyl)-2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 10.24% inhibition
N-(5,6-diphenylpyridazin-3-yl)-N'-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 88% inhibition
N-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 72% inhibition
N-(6-chloropyridazin-3-yl)-N'-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 83% inhibition
N-(6-methoxypyridazin-3-yl)-N'-(5-phenylpyridazin-3-yl)hexane-1,6-diamine
-
0.1 mg/ml, 83% inhibition
N-(benzyloxy)-2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 16.76% inhibition
N-ethylmaleimide
-
50% inhibition of ACAT1 at 0.5 mM
N-[2-(3,4-dimethylphenyl)ethyl]-2,3,6,8-tetramethoxy-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 11.86% inhibition
N-[3-(3,4-dimethoxyphenyl)propyl]-2,3,6,8-tetramethoxy-N-methyl-9-oxo-4,9-dihydro-1H-xanthene-5-sulfonamide
-
10 microgram/ml, 30.06% inhibition
naphthalene-1-carboxylic acid [3-(6-bromo-imidazo[1,2-a]pyridin-2-yl)-phenyl]-amide
-
48% inhibition at 0.025 mg/ml
naphthalene-2-carboxylic acid (3-[6-(2,4-difluoro-phenyl)-imidazo[1,2-a]pyridin-2-yl]-phenyl)-amide
-
23.6% inhibition at 0.025 mg/ml
naphthalene-2-carboxylic acid [3-(6-bromo-imidazo[1,2-a]pyridin-2-yl)-phenyl]-amide
-
56% inhibition at 0.025 mg/ml
naphthalene-2-carboxylic acid [3-(6-naphtalen-2-yl-imidazo-[1,2-a]pyridin-2-yl)-phenyl]-amide
-
7.1% inhibition at 0.025 mg/ml
octimibate
-
inhibits
oleic acid anilide
-
-
oleoyl-CoA
-
inhibits at high concentrations, the inhibition is prevented by serum albumin
Organic solvents
-
inhibit by perturbing the membrane structure
-
Organic solvents
-
-
-
p-chloromercuribenzene sulfonic acid
-
50% inhibition of ACAT1 at 0.01 mM, Cys467 is one of the major targets for inhibition
p-mercuribenzoate
-
100% inhibition of liver and aortic enzyme at 1 mM
pactimibe
-
-
-
pactimibe sulfate
-
CS-505
PD138412
-
recombinant enzyme, 80-90% inhibition at 0.003 mM
-
phenochalasin A
-
IC50: above 0.1 mM, ACAT1; IC50: above 0.1 mM, ACAT2
phenochalasin A
-
-
Phenylglyoxal
-
concentration-dependent inhibition of liver enzyme with 65% inhibition at 5 mM
phosphatidylinositol
-
-
phosphatidylserine
-
not inhibitory
phosphatidylserine
-
-
piperchabamide D
-
-
Polyoxyethylated cholesterol
-
-
-
Pregn-5-en-3beta-ol
-
inhibits esterification of endogenous cholesterol
pregnenolone
-
inhibits esterification of endogenous cholesterol
pregnenolone
-
-
progesterone
-
inhibits esterification of endogenous cholesterol reversibly
progesterone
-
-
progesterone
-
half-maximal inhibitory concentration of 0.05 mM
progesterone
-
50% inhibition at 0.02 mM
progesterone
-
-
purpactin A
-
IC50: 0.0009 mM, ACAT1; IC50: 0.0018 mM, ACAT2
purpactin B
-
IC50: 0.012 mM, ACAT2; IC50: 0.022 mM, ACAT1
purpactin C
-
IC50: 0.028 mM, ACAT1; IC50: 0.03 mM, ACAT2
pyripyropene A
-
IC50: 0.00006 mM, ACAT2; IC50: above 0.03 mM, ACAT1
pyripyropene A
-
-
pyripyropene A
-
specific inhibition. Method for isolation and purification from Penicillium griseofulvum F1959
pyripyropene B
-
IC50: 0.0008 mM, ACAT2; IC50: 0.03 mM, ACAT1
pyripyropene C
-
IC50: 0.00035 mM, ACAT2; IC50: 0.015 mM, ACAT1
pyripyropene D
-
IC50: 0.0012 mM, ACAT2; IC50: 0.015 mM, ACAT1
retrofractamide A
-
-
saucemeol B
-
0.125 mM, 57% inhibition; IC50: 0.043 mM
SC-31769
-
20-oxa analog of 7-ketosterol
SC-31769
-
20-oxa analog of 7-ketosterol
sespendole
-
IC50: 0.012 mM, ACAT2; IC50: 0.02 mM, ACAT1
shikonin
-
-
sitosterol
-
inhibits esterification of exogenous cholesterol
SM-32504
-
IC50: 11 nM
sphingomyelin
-
-
spylidone
-
IC50: 0.003 mM, ACAT2; IC50: 0.007 mM, ACAT1
SR144528
-
selective antagonist of cannobinoid receptor CB1. Additionally, reatment of cells reduces cholesteryl ester synthesis in unstimulated and acetylated low densitixy lipoprotein-stimulated Raw 264.7 macrophages, CB2 +/+ and CB2-/- peritoneal macrophages, as well as in vitro, in mouse liver microsomes. Consistent with inhibition of ACAT, the development of foam cell characteristics in macrophages by treatment with acetylated low density lipoprotein is reduced
stanolone
-
inhibits esterification of endogenous cholesterol
sterigmatocystin
-
; isolation from the culture broth of Aspergillus species, selective for isoform ACAT2
stigmasterol
-
inhibits esterification of exogenous cholesterol
terpendole C
-
IC50: 0.0005 mM, ACAT2; IC50: 0.008 mM, ACAT1
testosterone
-
inhibits esterification of endogenous cholesterol
testosterone
-
-
testosterone
-
-
Tetranitromethane
-
100% inhibition of liver and aortic enzyme at 1 mM
Triton WR1339
-
90% inhibition at 0.3% wt./vol.
VULM 1457
-
-
YM-750
-
-
[4-(2-(3-[(naphthalene-2-carbonyl)-amino]-phenyl)-imidazo[1,2-a]pyridin-6-yl)-phenoxy]-acetic acid
-
15% inhibition at 0.025 mg/ml
[4-(2-(3-[(naphthalene-2-carbonyl)-amino]-phenyl)-imidazo[1,2-a]pyridin-6-yl)-phenoxy]-acetic acid ethyl ester
-
8.7% inhibition at 0.025 mg/ml
[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate
-
pactimibe sulfate
Miconazole
-
50% inhibition at 0.0224 mM
additional information
-
corticosterone, cortisol and estriol have little effect, enzyme activity in placenta may be regulated by endogenously synthesized steroid hormones
-
additional information
-
enhancement of inactivation of the enzyme by ATP/Mg, NaF and a heat-labile cytosolic factor is consistent with a protein kinase-catalyzed phosphorilation being involved in the short term regulation of the enzyme
-
additional information
-
regulation by non-sterol agents
-
additional information
-
regulation by non-sterol agents; the inhibitor CI-976 given to cholesterol-fed rabbits prevents the accumulation of monocyte-macrophages within a pre-established iliac-femoral lesion and significantly reduces foam cell area
-
additional information
-
regulation by non-sterol agents
-
additional information
-
not inhibitory: polyoxin D, amphotericin B, nikkomycin Z
-
additional information
-
poly(ADP-ribose) polymerase inhibition in foam cells resulted in significant sensitization to 7-ketocholesterol by increasing cellular-toxic-free cholesterol, potentially through a down-regulation of ACAT-1 expression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
25-hydroxycholesterol
-
not stimulatory
25-hydroxycholesterol
-
activates
25-hydroxycholesterol
-
activates
25-hydroxycholesterol
-
stimulates enzyme activity in liver microsomes in vitro with half-maximal stimulation at 0.0168 mM oxysterol. A major part of the activation of microsomal enzyme is not ascribable to increased substrate availability for the enzyme
25-hydroxycholesterol
-
-
6-ketocholestanol
-
added at high concentration causes modest increase in enzyme activity
7-ketocholesterol
-
added at high concentration causes modest increase in enzyme activity
7-oxocholesterol
-
-
Albumin
-
-
-
Albumin
-
required in the assay medium to prevent the high concentration of oleoly-CoA from inhibiting the enzyme presumably by disrupting the microsomal membrane
-
Albumin
-
stimulates, effect is dependent on oleoyl-CoA concentration
-
Albumin
-
stimulates
-
Albumin
-
stimulates
-
Albumin
-
-
-
ATP
-
slight stimulation
cholate
-
increase of activity in cholate-fed animals
cholesterol
-
exogenous, delivered as a Triton WR-1339 detergent dispersion, increases activity
cholesterol
-
exogenous, not stimulatory
cholesterol
-
exogenous, not stimulatory
cholesterol
-
increase of activity in cholesterol-fed animals
cholesterol
-
exogenous, not stimulatory
cholesterol
-
exogenous, 25% increase of adrenal microsome activity and 2fold increase of activity in liver
cholesterol
-
exogenous, not stimulatory
cholesterol
-
exogenous, in liposomes or in organic solvent, stimulates
cholesterol
-
addition of cholesterol to frozen microsomes prepared from unfrozen liver tissue increases the enzyme activity; addition of cholesterol to microsomes prepared from frozen liver tissue does not further increase the enzyme activity
cholesterol
-
exogenous cholesterol in the liposomes is absolutely necessary for activity of the reconstituted enzyme
cholesterol
-
serves as an enzyme activator in vitro, in addition to its role as an enzyme substrate
cholesterol
-
exogenous, added as phosphatidylcholine liposome or in acetone solution, stimulates
cholesterol
-
-
cholesterol
-
day 40 samples, exogenous, added as phosphatidylcholine liposomes, concentration-dependent increase in activity; day 50 and 60 samples: not stimulatory
cholesterol
-
presence of cholesterol stimulates reaction of ACAT1 with sitosterol up to 3fold, reaction of ACAT2 is only moderately activated
cholesterol
-
significant activation of reaction with 7-ketocholesterol as substrate, decrease in Hill coefficient from 3.0 without cholesterol to 1.1 with cholesterol
cholesterol
-
ACAT2 is transcriptionally regulated by cholesterol
cholesterol
-
-
cholesterol
-
acts as a strong activator and as a substrate; acts as a strong activator and as a substrate
liver fatty acid binding protein/bovine serum albumin
-
small increase in activity
-
low density lipoprotein
-
increase of activity
-
low density lipoprotein
Q61263
-
-
phosphatidylethanolamine
-
weak stimulatory effect on activity
sitosterol
-
; weak activator
TNF-alpha
-
up-regulating of ACAT1 expression
-
Mevalonolactone
-
intragastric administration, increasing sterol biosynthesis and increasing enzyme activity
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00163
cholesterol
-
-
0.06
cholesterol
-
with oleoyl-CoA
0.0022
Elaidoyl-CoA
-
-
0.0013
oleoyl-CoA
-
pH and temperature not specified in the publication
0.004
oleoyl-CoA
-
-
0.004
oleoyl-CoA
-
-
0.00462
oleoyl-CoA
-
-
0.0071
oleoyl-CoA
-
wild-type enzyme
0.0072
oleoyl-CoA
-
HisACAT1, mutant HisACAT1/P64
0.00999
oleoyl-CoA
-
-
0.0154
oleoyl-CoA
-
mutant HisACAT1/1-65
0.025
oleoyl-CoA
-
bound to acyl-CoA binding protein
0.03
oleoyl-CoA
-
in the absence of acyl-CoA binding protein
0.038
oleoyl-CoA
-
-
0.055
oleoyl-CoA
-
-
0.069
oleoyl-CoA
-
-
0.00000266
oleyl-CoA
-
pyripyropene A-insensitive chimera A2:1-479
0.00000333
oleyl-CoA
-
pyripyropene A-insensitive chimera A2:1-428
0.00000553
oleyl-CoA
-
wild typeACAT2
0.00000587
oleyl-CoA
-
pyripyropene A-insensitive mutant A2S494C
0.000008094
oleyl-CoA
-
pyripyropene A-insensitive mutant A2V493L
0.00001218
oleyl-CoA
-
pyripyropene A-insensitive mutant A2Q492L
0.038
palmitoyl-CoA
-
-
0.0012
pregnenolone
-
pH 7.4, 37C, with cholesterol (0.32 mM). Without cholesterol, the Km for pregnenolone is too high to be measurable
0.0064
stearoyl-CoA
-
pH and temperature not specified in the publication
0.0028
linoleoyl-CoA
-
-
additional information
additional information
-
-
-
additional information
additional information
-
use of kinetic parameters such as Km is of limited value due to the physical properties of oleoyl-CoA in solution and the addition of serum albumin to the assay
-
additional information
additional information
-
-
-
additional information
additional information
-
for the various Cys-deficient mutant ACAT1s, the Km value for oleoyl-coenzyme A is approximately 2fold higher than the value for the wild-type enzyme, ranging between 0.012 und 0.015 mM
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00006
(6R,9S,13S)-3-benzyl-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.00009
(6R,9S,13S)-3-benzyl-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.001
(6S,9S,13R)-9-(2-chlorobenzyl)-6-methyl-3-[(1S)-1-methylpropyl]-13-pentyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.04
(6S,9S,13R)-9-(2-chlorobenzyl)-6-methyl-3-[(1S)-1-methylpropyl]-13-pentyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.00025
(6S,9S,13S)-6-methyl-13-[(1S)-1-methylnonyl]-3-[(1S)-1-methylpropyl]-9-(naphthalen-2-ylmethyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.02
(6S,9S,13S)-6-methyl-13-[(1S)-1-methylnonyl]-3-[(1S)-1-methylpropyl]-9-(naphthalen-2-ylmethyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.0001
(6S,9S,13S)-6-methyl-9-(4-methylbenzyl)-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.004
(6S,9S,13S)-6-methyl-9-(4-methylbenzyl)-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.00015
(6S,9S,13S)-9-(3-chlorobenzyl)-6-methyl-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.0065
(6S,9S,13S)-9-(3-chlorobenzyl)-6-methyl-13-[(1S)-1-methylbutyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.0001
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1R)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.004
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1R)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.00027
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT2, 37C
0.01
(6S,9S,13S)-9-(diphenylmethyl)-6-methyl-13-[(1S)-1-methylpentyl]-3-[(1S)-1-methylpropyl]-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
-
isoform ACAT1, 37C
0.000378
2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
-
inhibition is competitive with respect to oleoyl-coenzyme A
0.05
20alpha-hydroxypregn-4-en-3-one
-
-
0.5
Acetic anhydride
-
less than, aortic enzyme
5
Acetic anhydride
-
greater than, liver enzyme
0.026
CI-976
-
-
0.04
diethyl dicarbonate
-
aortic enzyme
1.5
diethyl dicarbonate
-
liver enzyme
0.00515
HWY-289
-
-
0.039
Miconazole
-
-
0.05
progesterone
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0138
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-methylbutanoate
-
-
0.0251
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-methylbutanoate
-
-
0.0537
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl benzoate
-
-
0.0562
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl benzoate
-
-
0.0496
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl butanoate
-
-
0.0776
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl butanoate
-
-
0.0307
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pent-4-enoate
-
-
0.0714
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pent-4-enoate
-
-
0.0845
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pentanoate
-
-
0.0948
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl pentanoate
-
-
0.0224
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl propanoate
-
-
0.025
(24R)-ethylcholest-5-ene-3,7-diol
-
-
0.000025
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-6-(pentanoyloxy)-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-3-yl benzoate
-
isoform ACAT1, cell-based assay
0.000062
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-6-(pentanoyloxy)-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-3-yl benzoate
-
isoform ACAT2, cell-based assay
0.00001
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl dipentanoate
-
isoform ACAT1, cell-based assay
0.00007
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-12,12b-dihydroxy-4,6a-dimethyl-4-[[(methylsulfonyl)oxy]methyl]-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl dipentanoate
-
isoform ACAT2, cell-based assay
0.000006
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl 3-methylbutanoate
-
isoform ACAT2, cell-based assay
0.0035
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl 3-methylbutanoate
-
isoform ACAT1, cell-based assay
0.00007
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate
-
isoform ACAT2, cell-based assay
0.08
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate
-
isoform ACAT1, cell-based assay
0.000012
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-3-(butanoyloxy)-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl hexanoate
-
isoform ACAT2, cell-based assay
0.00001
(3S,4S,4aR,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-4,12,12b-trihydroxy-6a-methyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl (2E)-pent-2-enoate
-
isoform ACAT2, cell-based assay
0.00001
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(1-methylethyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT2, cell-based assay
0.0007
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(1-methylethyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT1, cell-based assay
0.00001
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(2-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT2, cell-based assay
0.0032
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(2-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT1, cell-based assay
0.00001
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(4-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT2, cell-based assay
0.000113
(S)-7-dimethylamino-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-isobutyryl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
-
pH 7.4, 37C
0.00068
1-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]-3-{4-[(ethylamino)methyl]-2,6-bis(1-methylethyl)phenyl}urea
-
IC50: 680 nM
0.0000054
1-[2,4-bis(1-methylethyl)pyridin-3-yl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]urea
-
IC50: 5.4 nM
0.000043
1-[3-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 43 nM
0.000382
1-[4-(aminomethyl)-2,6-bis(1-methylethyl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl]urea
-
IC50: 382 nM
0.000452
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-(1-butyl-4-{3-[3-(ethylamino)propoxy]phenyl}-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl)urea
-
IC50: 452 nM
0.00054
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-2-oxo-4-[3-(3-piperidin-1-ylpropoxy)phenyl]-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 540 nM
0.000427
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-2-oxo-4-[3-(3-pyrrolidin-1-ylpropoxy)phenyl]-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 427 nM
0.000021
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
i.e. SMP-797, possessing a potent ACAT inhibitory activity and significantly enhanced aqueous solubility under acidic conditions. The compound is a promising agent for oral treatment of hypercholesterolemia.IC50: 21 nM
0.000061
1-[4-amino-2,6-bis(1-methylethyl)phenyl]-3-{1-butyl-4-[3-(4-hydroxybutoxy)phenyl]-2-oxo-1,2,4a,8a-tetrahydro-1,8-naphthyridin-3-yl}urea
-
IC50: 61 nM
0.000018
1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-({1-[2-(3-hydroxypropoxy)phenyl]-4-(3-methoxyphenyl)piperidin-4-yl}methyl)urea
-
pH 7.4
0.000032
1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-{[1-(2-butoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl}urea
-
pH 7.4
0.0281
2-[(2E,6Z,8E,10E)-dodeca-2,6,8,10-tetraenoylamino]-1,1-dimethylethyl acetate
-
IC50: 0.0281 mM
0.0875
2-[(2E,6Z,8E,10E)-dodeca-2,6,8,10-tetraenoylamino]-1,1-dimethylethyl acetate
-
IC50: 0.0875 mM
0.000068
2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
-
inhibition of cholesterol esterification in human monocyte-derived macrophages
0.00045
2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
-
recombinant ACAT-1, K-604 is 229-fold more selective for ACAT-1 than for ACAT-2
0.1028
2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
-
recombinant ACAT-2
0.0115
3beta-hydroxylup-20(29)-en-28-oic acid
-
-
0.0339
3beta-hydroxylup-20(29)-en-28-oic acid
-
-
0.16
5,5'-dibutoxy-2,2'-bifuran
-
-
0.19
5,5'-dibutoxy-2,2'-bifuran
-
-
0.017
5-(1-butoxy-2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}propyl)-1,3-benzodioxole
-
IC50: 0.017 mM
0.031
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-ethoxypropyl)-1,3-benzodioxole
-
IC50: 0.031 mM
0.035
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-methoxypropyl)-1,3-benzodioxole
-
IC50: 0.035 mM
0.014
5-(2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-propoxypropyl)-1,3-benzodioxole
-
IC50: 0.014 mM
0.05
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(heptyloxy)propyl]-1,3-benzodioxole
-
IC50: 0.05 mM
0.034
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(hexyloxy)propyl]-1,3-benzodioxole
-
IC50: 0.034 mM
0.02
5-[2-{4-[(2S,3R,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyltetrahydrofuran-2-yl]-2-methoxyphenoxy}-1-(pentyloxy)propyl]-1,3-benzodioxole
-
IC50: 0.02 mM
0.0387
5alpha,8alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3beta-ol
-
-
0.2
5alpha,8alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3beta-ol
-
-
0.1122
acetylshikonin
-
-
0.1289
acetylshikonin
-
-
0.0015
aurasperone A
-
isoform ACAT2, 37C, cell-based assay
0.006
aurasperone A
-
isoform ACAT1, 37C, cell-based assay
0.0015
aurasperone D
-
isoform ACAT2, 37C, cell-based assay
0.007
aurasperone D
-
isoform ACAT1, 37C, cell-based assay
0.0043
avasimibe
-
macrophage
0.0082
avasimibe
-
liver
0.0092
avasimibe
-
ACAT-2
0.014
avasimibe
-
THP-1 cell
0.0235
avasimibe
-
ACAT-1
0.012
averufanin
-
isoform ACAT2, 37C, cell-based assay
0.0218
averufanin
-
isoform ACAT1, 37C, cell-based assay
0.00013
beauvericin
-
-
0.00035
beauvericin
-
IC50: 0.00035 mM, ACAT1; IC50: 0.00035 mM, ACAT2
0.00035
beauvericin
-
enzyme assay
0.0007
beauvericin
-
cell-based assay
0.002
beauvericin
-
cell-based assay
0.0006
beauveriolide I
-
cell-based assay
0.00078
beauveriolide I
-
-
0.0019
beauveriolide I
-
IC50: 0.0019 mM, ACAT2
0.0019
beauveriolide I
-
enzyme assay
0.0022
beauveriolide I
-
IC50: 0.0022 mM, ACAT1
0.0022
beauveriolide I
-
enzyme assay
0.02
beauveriolide I
-
cell-based assay
0.00041
beauveriolide III
-
-
0.0009
beauveriolide III
-
cell-based assay
0.003
beauveriolide III
-
IC50: 0.003 mM, ACAT1; IC50: 0.003 mM, ACAT2
0.003
beauveriolide III
-
enzyme assay
0.02
beauveriolide III
-
cell-based assay
0.1698
beta-hydroxyisovalerylshikonin
-
-
0.1869
beta-hydroxyisovalerylshikonin
-
-
0.012
beta-sanshool
-
; IC50: 0.012 mM
0.039
beta-sanshool
-
; IC50: 0.039 mM
0.0281
beta-sanshool acetate
-
-
0.0875
beta-sanshool acetate
-
-
0.083
betulin
-
IC50: 0.083 mM, hACAT-1
0.01872
CI-1011
-
recombinant ACAT-1
0.01911
CI-1011
-
recombinant ACAT-2
0.00006
CL-283,546
-
IC50: 0.00006 mM, ACAT2
0.00006
CL-283,546
-
enzyme assay
0.00009
CL-283,546
-
cell-based assay
0.0001
CL-283,546
-
cell-based assay
0.00012
CL-283,546
-
IC50: 0.00012 mM, ACAT1
0.00012
CL-283,546
-
enzyme assay
0.09
dehydropipernonaline
-
-
0.06
dehydroretrofractamide
-
-
0.006
flavasperone
-
isoform ACAT2, 37C, cell-based assay
0.0797
gamma-sanshool
-
; IC50: 0.0797 mM
0.0826
gamma-sanshool
-
; IC50: 0.0826 mM
0.0246
glabrol
-
-
0.026
glabrol
-
-
0.0004
glisoprenin A
-
IC50: 0.0004 mM, ACAT1
0.0004
glisoprenin A
-
enzyme assay
0.0013
glisoprenin A
-
IC50: 0.0013 mM, ACAT2
0.0013
glisoprenin A
-
enzyme assay
0.0043
glisoprenin A
-
cell-based assay
0.01
glisoprenin A
-
cell-based assay
0.012
glisoprenin A
-
-
0.0575
isobutyrylshikonin
-
-
0.1
K-604
Q61263, Q88908
isoform ACAT-1, semniferous tubules
1
K-604
Q61263, Q88908
isoform ACAT-2, semniferous tubules
0.0015
K97-0239A
-
-
0.009
K97-0239A
-
cell-based assay
0.013
K97-0239A
-
cell-based assay
0.038
K97-0239A
-
IC50: 0.038 mM, ACAT2
0.038
K97-0239A
-
enzyme assay
0.04
K97-0239A
-
IC50: 0.04 mM, ACAT1
0.04
K97-0239A
-
enzyme assay
0.0017
K97-0239B
-
-
0.013
K97-0239B
-
cell-based assay
0.07
K97-0239B
-
IC50: above 0.07 mM, ACAT1
0.07
K97-0239B
-
enzyme assay
0.7
K97-0239B
-
IC50: above 0.7 mM, ACAT2
0.048
lupeol
-
IC50: 0.048 mM, hACAT-1
0.0000532
N-(4-amino-2,6-diisopropylphenyl)-N'-([1-(2-butoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]-methyl)urea
-
pH 7.4
0.0152
oleic acid anilide
-
inhibited ACAT activity in THP-1 macrophages
0.000312
pactimibe
-
pH 7.4, 37C
-
0.002
pactimibe sulfate
-
liver
0.0027
pactimibe sulfate
-
macrophage
0.003
pactimibe sulfate
-
ACAT-2
0.0047
pactimibe sulfate
-
THP-1 cell
0.0049
pactimibe sulfate
-
ACAT-1
0.0405
pellitorin
-
-
0.0006
phenochalasin A
-
-
0.02
phenochalasin A
-
cell-based assay
0.1
phenochalasin A
-
IC50: above 0.1 mM, ACAT1; IC50: above 0.1 mM, ACAT2
0.1
phenochalasin A
-
enzyme assay
0.0135
piperchabamide D
-
-
0.0037
pipercide
-
-
0.0009
purpactin A
-
IC50: 0.0009 mM, ACAT1
0.0009
purpactin A
-
enzyme assay
0.0015
purpactin A
-
cell-based assay
0.0018
purpactin A
-
IC50: 0.0018 mM, ACAT2
0.0018
purpactin A
-
enzyme assay
0.0025
purpactin A
-
cell-based assay
0.0045
purpactin A
-
-
0.0022
purpactin B
-
enzyme assay
0.0057
purpactin B
-
cell-based assay
0.01
purpactin B
-
cell-based assay
0.012
purpactin B
-
IC50: 0.012 mM, ACAT2
0.012
purpactin B
-
enzyme assay
0.02
purpactin B
-
-
0.022
purpactin B
-
IC50: 0.022 mM, ACAT1
0.0028
purpactin C
-
enzyme assay
0.01
purpactin C
-
cell-based assay
0.018
purpactin C
-
-
0.028
purpactin C
-
IC50: 0.028 mM, ACAT1
0.03
purpactin C
-
IC50: 0.03 mM, ACAT2
0.03
purpactin C
-
enzyme assay
0.00006
pyripyropene A
-
IC50: 0.00006 mM, ACAT2
0.00006
pyripyropene A
-
enzyme assay
0.00007
pyripyropene A
-
cell-based assay
0.03
pyripyropene A
-
IC50: above 0.03 mM, ACAT1
0.03
pyripyropene A
-
enzyme assay
0.08
pyripyropene A
-
cell-based assay
0.08
pyripyropene A
-
-
0.0008
pyripyropene B
-
IC50: 0.0008 mM, ACAT2
0.0008
pyripyropene B
-
enzyme assay
0.002
pyripyropene B
-
cell-based assay
0.03
pyripyropene B
-
IC50: 0.03 mM, ACAT1
0.03
pyripyropene B
-
enzyme assay
0.038
pyripyropene B
-
-
0.048
pyripyropene B
-
cell-based assay
0.00035
pyripyropene C
-
IC50: 0.00035 mM, ACAT2
0.00035
pyripyropene C
-
enzyme assay
0.00036
pyripyropene C
-
cell-based assay
0.015
pyripyropene C
-
IC50: 0.015 mM, ACAT1
0.015
pyripyropene C
-
enzyme assay
0.032
pyripyropene C
-
cell-based assay
0.04
pyripyropene C
-
-
0.0012
pyripyropene D
-
IC50: 0.0012 mM, ACAT2
0.0012
pyripyropene D
-
enzyme assay
0.0015
pyripyropene D
-
cell-based assay
0.015
pyripyropene D
-
IC50: 0.015 mM, ACAT1
0.015
pyripyropene D
-
enzyme assay
0.035
pyripyropene D
-
-
0.038
pyripyropene D
-
cell-based assay
0.0245
retrofractamide A
-
-
0.043
saucemeol B
-
IC50: 0.043 mM
0.004
sespendole
-
-
0.0065
sespendole
-
cell-based assay
0.012
sespendole
-
IC50: 0.012 mM, ACAT2
0.012
sespendole
-
cell-based assay; enzyme assay
0.02
sespendole
-
IC50: 0.02 mM, ACAT1
0.02
sespendole
-
enzyme assay
0.0704
shikonin
-
-
0.1382
shikonin
-
-
0.000011
SM-32504
-
IC50: 11 nM
0.000031
SMP-797
-
-
0.003
spylidone
-
IC50: 0.003 mM, ACAT2
0.003
spylidone
-
enzyme assay
0.005
spylidone
-
cell-based assay
0.007
spylidone
-
IC50: 0.007 mM, ACAT1
0.007
spylidone
-
enzyme assay
0.025
spylidone
-
cell-based assay
0.042
spylidone
-
-
0.0024
sterigmatocystin
-
isoform ACAT2, 37C, cell-based assay
0.03
sterigmatocystin
-
isoform ACAT1, 37C, cell-based assay
0.0005
terpendole C
-
IC50: 0.0005 mM, ACAT2
0.0005
terpendole C
-
enzyme assay
0.0025
terpendole C
-
-
0.008
terpendole C
-
IC50: 0.008 mM, ACAT1
0.008
terpendole C
-
enzyme assay
0.01
terpendole C
-
cell-based assay
0.00069
[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate
-
hepatic ACAT
0.00072
[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate
-
intestinal ACAT
0.0019
[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate
-
macrophage ACAT
0.0159
[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate
-
adrenal ACAT
0.0287
(1R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl propanoate
-
-
additional information
(1R,3R,7R)-1-[(1S)-1-hydroxypropyl]-3,7-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]heptan-5-one
-
45% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
additional information
(1R,3R,7S)-1-[(1S)-1-hydroxypropyl]-3,7-diphenyl-6-[(1S)-1-phenylethyl]-2-oxa-6-azaspiro[3.3]heptan-5-one
-
66% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
0.102
(24R)-ethylcholest-5-ene-3,7-diol
-
-
additional information
(3R,5S,7S,8R)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1R)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
27% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
0.0028
(3S,4R,4aS,6S,6aS,12R,12aR,12bR)-4-[(acetyloxy)methyl]-3-(butanoyloxy)-12,12b-dihydroxy-4,6a-dimethyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl hexanoate
-
isoform ACAT1, cell-based assay
additional information
(3S,4S)-3-[(1R,2R)-2-azido-1-hydroxybutyl]-3-bromo-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
65% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
additional information
(3S,4S)-3-[(1S,2S)-2-azido-1-hydroxybutyl]-3-bromo-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
60% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
0.0042
(3S,4S,4aR,6S,6aS,12R,12aR,12bR)-3-(acetyloxy)-4-[(acetyloxy)methyl]-4,12,12b-trihydroxy-6a-methyl-11-oxo-9-pyridin-3-yl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-6-yl (2E)-pent-2-enoate
-
isoform ACAT1, cell-based assay
additional information
(3S,5S,7S,8R)-7-ethyl-8-hydroxy-3,5-diphenyl-2-[(1R)-1-phenylethyl]-6-oxa-2-azaspiro[3.4]octan-1-one
-
23% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
0.0038
(4aR,4bS,6S,6aS,12R,12aR,12bR,14aS)-12,12b-dihydroxy-4a,6a-dimethyl-2-(4-methylphenyl)-11-oxo-9-pyridin-3-yl-4,4a,4b,5,6,6a,12,12a,12b,13,14,14a-dodecahydro-11H-pyrano[4',3':2,3]chromeno[6,5-f][1,3]benzodioxin-6-yl pentanoate
-
isoform ACAT1, cell-based assay
additional information
(4S)-3-[(1R,2S)-2-azido-1-hydroxybutyl]-3-[(S)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
87% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
additional information
(4S)-3-[(1S,2R)-2-azido-1-hydroxybutyl]-3-[(R)-hydroxy(phenyl)methyl]-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-2-one
-
79% inhibition, reference standard lovastatin, literature data reference IC50 = 0.012 mM, 0.0168 mM when concurrently tested
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000053 - 0.000008
-
-
0.0000178
-
microsomal preparation
0.0000222
-
microsomes
0.0000293
-
ACAT2 activity, effect on ChSI on hepatic ACAT2 expression, high cholesterol synthesis inhibition, high ChSI
0.0000333
-
ACAT2 activity, effect on ChSI on hepatic ACAT2 expression, low cholesterol synthesis inhibition, low ChSI
0.0000377
-
ACAT2 activity, effect on cholesterol synthesis inhibition on hepatic ACAT2 expression, placebo
0.00005
-
whole homogenate of biopsies from distal duodenum-proximal jejunum
0.000053
-
microsomal preparations from ileum, mean value
0.0000582
-
microsomal fraction without 25-hydroycholesterol
0.00006
-
cholesterol added in Tween 80
0.000062
-
microsomal preparations from duodenum, mean value
0.000063
-
cholesterol added in acetone
0.00008
-
solubilized enzyme
0.000081
-
ACAT activity in liver, 100 mg/kg/day esculeoside A
0.000088
-
ACAT activity in peritoneal macrophage, 100 mg/kg/day esculeoside A
0.000089
-
microsomes + 5 mM ATP + 50 mM NaF + 5 mM MgCl2 + 0.005 mM cAMP + 0.005 mg protein kinase
0.000093
-
microsomes + 5 mM ATP
0.0000982
-
microsomal fraction with 25-hydroycholesterol
0.000099
-
microsomes + 5 mM ATP + 50 mM NaF + 5 mM MgCl2
0.0001042
-
aortic microsomal preparation
0.000117
-
control microsomes
0.000126
-
microsomes + 5 mM MgCl2 + 50 mM NaF
0.000132
-
microsomes + 50 mM NaF
0.000144
-
ACAT activity in intestine, 100 mg/kg/day esculeoside A; ACAT activity in intestine, control
0.00015
-
kidney microsomes
0.00015
-
ACAT activity in peritoneal macrophage, control
0.000156
-
ACAT activity in liver, control
0.000169
-
microsomes + 5 mM MgCl2
0.00021
-
microsomal preparations from jejunum, mean value
0.000368
-
day 30 of development, endogenous cholesterol as substrate
0.000808
-
microsomal preparation from day 40 of development measured at 33C
0.000824
-
microsomal preparation from day 40 of development measured at 37C
0.00087
-
small intestine microsomes
0.0009
-
recombinant enzyme
0.0012
-
recombinant enzyme ACAT1, vector: pcDNA3+, cell type: AC29
0.00135
-
liver microsomes
0.001585
-
day 50 of development, endogenous cholesterol as substrate
0.0017
-
liver microsomes
0.0019
-
recombinant enzyme ACAT2, vector: pCMV5, cell type: AC29
0.0022
-
recombinant enzyme ACAT2, vector: pcDNA3+, cell type: AC29
0.0037
-
adrenal microsomes
0.0038
-
recombinant enzyme ACAT2, vector: pcDNA3+, cell type: COS
0.00561
-
TNFalpha treatment, duration 1 h
0.00562
-
TNFalpha treatment, duration 0.5 h; TNFalpha treatment, duration 0 h
0.00842
-
TNFalpha treatment, duration 2 h
0.00868
-
TNFalpha treatment, duration 6 h
0.0102
-
TNFalpha treatment, duration 12 h
0.01121
-
TNFalpha treatment, duration 24 h
0.0127
-
ACAT2 activity in HuH-7 cells, control
0.015
-
partially purified enzyme
0.0192
-
ACAT2 activity in HuH-7 cells, 30 microM HDL cholesterol
0.02041
-
TNFalpha treatment, duration 48 h
0.0347
-
ACAT2 activity in HuH-7 cells, 0.5 mM LDL cholesterol
0.039
-
ACAT2 activity in HuH-7 cells, control
0.0558
-
ACAT1 activity in HuH-7 cells, control
0.0701
-
ACAT1 activity in HuH-7 cells, 0.5 mM LDL cholesterol
0.086
-
ACAT1 activity in HuH-7 cells, control
0.0946
-
ACAT2 activity in HuH-7 cells, 0.1 mM free cholesterol
0.1102
-
ACAT1 activity in HuH-7 cells, 0.1 mM free cholesterol
0.1861
-
ACAT1 activity in HuH-7 cells, 30 microM HDL cholesterol
3.5 - 4
-
purified recombinant enzyme
2210
-
ACAT2 activity in Hep-G2 cells, control
3220
-
ACAT2 activity in Hep-G2 cells, control
4650
-
ACAT1 activity in Hep-G2 cells, 1.5 mM LDL cholesterol
4730
-
ACAT1 activity in Hep-G2 cells, 1 mM HDL cholesterol
4980
-
ACAT1 activity in Hep-G2 cells, control
5030
-
ACAT2 activity in Hep-G2 cells, 1.5 mM LDL cholesterol
5750
-
ACAT1 activity in Hep-G2 cells, control
5810
-
ACAT1 activity in Hep-G2 cells, 0.9 mM free cholesterol
6230
-
ACAT2 activity in Hep-G2 cells, 1 mM HDL cholesterol
9560
-
ACAT2 activity in Hep-G2 cells, 0.9 mM free cholesterol
additional information
-
-
additional information
-
assay method
additional information
-
-
additional information
-
assay method
additional information
-
overview: normal and cholesterol-fed organs
additional information
-
overview: effect of fasting, feeding with cholesterol or cholate, atherogenic diet administration of Triton WR 1339 and administration of mevanolactone, evidence for a circadian rhythm
additional information
-
overview: specific activities in microsomes stored at -40C for up to 6 weeeks
additional information
-
enhancement of activity following 8-11 weeks of cholesterol feeding
additional information
-
-
additional information
-
comparison of enzyme activities of cells grown in fetal calf serum medium and in delipidated serum medium
additional information
-
overview: enzyme activity under various conditions
additional information
-
-
additional information
-
comparison of enzyme activities of cells grown in fetal calf serum medium and in delipidated serum medium
additional information
-
activation of the enzyme by adding 25-hydroxycholesterol to intact cells or to cell-free extracts
additional information
-
when yeast-expressed enzyme activity is measured in the presence of ergosterol liposomes, specific activity is reduced more than 80%, recombinant enzyme is active but unable to esterify ergosterol efficiently
additional information
-
enhancement of activity following 8-11 weeks of cholesterol feeding
additional information
-
-
additional information
-
overview: enzyme activity at various days of development with and without exogenous cholesterol
additional information
-
the enzyme activity of a stable clone of H293 cells expressing HisACAT1/Flag is about 9-10times higher than that of a stable clone of CHO cells either expressing hACAT1 or expressing HisACAT1
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
-
activity assay
7.4
-
activity assay
7.4
-
activity assay
7.4
-
assay at
7.4
-
assay at; assay at
7.8
-
ACAT activity assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.6 - 7.4
-
2fold higher activity at pH 5.6 than at pH 7.4
6.5 - 8.4
-
pH 6.5: 55% of activity maximum, pH 8.4: 75% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
assay at
33
-
assay at, the reaction rate is not significantly different from that at 37C
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
Q61263
assay at
37
-
assay at
37
P53629
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
activity assay
37
-
activity assay
37
-
ACAT activity assay
37
-
activity assay
37
-
microsomal ACAT assay
37
-
activity assay
37
-
microsomal ACAT assay
37
-
activity assay
37
-
activity assay
37
-
assay at; assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q61263
low expression
Manually annotated by BRENDA team
-
ACAT1 enzyme, high mRNA signal
Manually annotated by BRENDA team
Q61263
highly expressed
Manually annotated by BRENDA team
-
1.7fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
highest activity and highest mRNA level, significant immunohistochemical reactivity
Manually annotated by BRENDA team
-
ACAT1 enzyme, highest mRNA signal
Manually annotated by BRENDA team
-
ACAT1: strongly present in the cells of the cortex
Manually annotated by BRENDA team
-
41fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
atheroschlerotic tissue
Manually annotated by BRENDA team
-
extremely low activity
Manually annotated by BRENDA team
Q61263
low expression
Manually annotated by BRENDA team
-
1.6fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
CHO cells, cultured cells
Manually annotated by BRENDA team
-
ACAT1, distal tubules and podocytes
Manually annotated by BRENDA team
Q61263
low expression
Manually annotated by BRENDA team
-
ACAT1 enzyme, high mRNA signal
Manually annotated by BRENDA team
-
6fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
the CDX2 (caudal type homeobox transcription factor 2) expression is elevated, accounting for its elevated ACAT2 expression
Manually annotated by BRENDA team
-
high percentage (seven of fourteen) of liver samples from patients affected with hepatocellular carcinoma exhibit elevated ACAT2 expression
Manually annotated by BRENDA team
-
two different forms of the enzyme are present, ACAT1 and ACAT2
Manually annotated by BRENDA team
-
23fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
high activity, high mRNA level, significant immunohistochemical reactivity
Manually annotated by BRENDA team
-
expression of ACAT2 mRNA
Manually annotated by BRENDA team
-
ACAT2: strongly present in the apical third of the mucosal cells, ACAT1: strong signal in goblet cells, Paneth cells and villus macrophages
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
microsomal preparation, highest activity
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
ACAT1 enzyme, high mRNA signal
Manually annotated by BRENDA team
-
ACAT1 present
Manually annotated by BRENDA team
-
27fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
the enzyme activity is very low in fetal livers but is largely induced shortly after birth
Manually annotated by BRENDA team
-
expression of ACAT2 mRNA. ACAT1 enzyme: high mRNA signal
Manually annotated by BRENDA team
-
nonparenchymal cells contain 30fold more enzyme message than parenchymal cells
Manually annotated by BRENDA team
-
high activity, extremely low mRNA level and negligible immunohistochemical reactivity
Manually annotated by BRENDA team
Q61263
enzyme levels are doubled in animals fed an atherogenic diet
Manually annotated by BRENDA team
-
isoform ACAT2, high expression
Manually annotated by BRENDA team
O88908
hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins
Manually annotated by BRENDA team
-
in normal adult human liver, CDX2 (caudal type homeobox transcription factor 2) expression is not detectable and the ACAT2 expression is very low
Manually annotated by BRENDA team
-
increased ACAT activity with progressive age
Manually annotated by BRENDA team
Mus musculus C57B1/6
-
increased ACAT activity with progressive age
-
Manually annotated by BRENDA team
Rattus norvegicus male Wistar, Rattus norvegicus male Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
3fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
relative high level of mRNA
Manually annotated by BRENDA team
-
ACAT1, villus
Manually annotated by BRENDA team
-
loss of ACAT activity in macrophages, either by pharmacological inhibition or by genetic knockout of ACAT-1, results in reduced induction of apoptosis in response to 7-ketocholesterol or oxidized low density lipoproteins. The apoptotic signal generated in macrophages by ACAT may be an arachidonyl oxysterol
Manually annotated by BRENDA team
-
monocyte-derived macrophage
Manually annotated by BRENDA team
-
primary isoform expressed is ACAT1
Manually annotated by BRENDA team
-
serotonin upregiulates ACAT-1 expression in human monocyte-macrophages
Manually annotated by BRENDA team
-
25fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
ACAT1 enzyme, high mRNA signal
Manually annotated by BRENDA team
Q61263
highly expressed
Manually annotated by BRENDA team
Q61263
low expression
Manually annotated by BRENDA team
-
isoform ACAT2, high expression
Manually annotated by BRENDA team
-
7fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
1.8fold induction of activity after 60 days of cholesterol feeding
Manually annotated by BRENDA team
-
THP-1 cell-derived foam cell
Manually annotated by BRENDA team
-
ACAT1 enzyme, high mRNA signal
Manually annotated by BRENDA team
-
embryo, membrane, at various stages of development
Manually annotated by BRENDA team
additional information
-
overview: enzyme activity in normal and cholesterol-fed organs, identification of two distinct tissue types of the enzyme
Manually annotated by BRENDA team
additional information
Q61263
effect of an atherogenic diet upon hepatic and intestinal enzyme mRNA expression and on enzyme mRNA expression in aorta and peritoneal macrophages. Enzyme activity in the liver is regulated at least in part by enzyme mRNA abundance
Manually annotated by BRENDA team
additional information
-
isoform ACAT1, present in all tissues examined
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
approximately 10-15% of the enzyme in freshly harvested, non-attached macrophages is exposed to the extracellular space
Manually annotated by BRENDA team
-
reticular/nuclear
-
Manually annotated by BRENDA team
-
little activity
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
little activity
-
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
rough, membranes
-
Manually annotated by BRENDA team
-
cytoplasmic surface of
-
Manually annotated by BRENDA team
-
submicrosomal distribution
-
Manually annotated by BRENDA team
-
submicrosomal distribution
-
Manually annotated by BRENDA team
-
intrinsic membrane enzyme, highest activity
-
Manually annotated by BRENDA team
Mus musculus C57B1/6
-
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus male Wistar
-
submicrosomal distribution
-
-
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
intrinsic membrane enzyme, highest activity
-
-
Manually annotated by BRENDA team
Rattus norvegicus male Sprague-Dawley
-
little activity
-
Manually annotated by BRENDA team
additional information
-
-
-
Manually annotated by BRENDA team
additional information
-
cholesterol flux into and out of the endoplasmic reticulum
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
44000
-
determined by SDS-PAGE and Western Blot analysis
684800
47000
-
immunoblotting, ACAT2 enzyme
486708
50000
-
immunoblotting, ACAT1 enzyme and Cys-mutants
486709
50000
-
determined by SDS-PAGE and Western Blot analysis
684786
52000
-
recombinant enzyme
486700
53000
-
immunoblotting, ACAT1 enzyme
486708
56000
-
SDS-PAGE
718887
63700
-
deduced from amino acid sequence data
486699
64000
Q61263
deduced from amino acid sequence data
486698
64000
-
deduced from amino acid sequence data
486704
64810
-
deduced from the ORF analysis of enzyme cDNA
486695
64810
-
-
486703
71600
P53629
deduced from amino acid sequence data
486700
213000
-
approximately, liver membranes, radiation inactivation analysis
486703
additional information
-
expected monomer molecular masses of different fusion proteins range between 33000 and 41000 Da, sucrose density gradient velocity ultracentrifugation shows molecular masses of different fusion proteins ranging from 70000 to 160000 Da, thus some fusion proteins behave as tetramers in solution and other behave as dimers in solution
486710
additional information
-
method to quantify and map the disulfide linkage. Cys92 is located on the cytoplasmic side of the endoplasmic reticulum membrane and the disulfide is located in the ER lumen, while all other free Cys are located within the hydrophobic regions of the enzyme
672028
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 58000, SDS-PAGE
?
-
x * 45000-50000, SDS-PAGE
?
-
x * 64000, denaturing electrophoresis conditions
?
-
x * 71300, calculated, x * 71000, SDS-PAGE
homotetramer
-
use of chemical cross-linking agent disuccinimidyl suberate causes the formation of material two to four times the size of the monomeric enzyme when added to intact cells expressing either wild-type ACAT1 or mutant ACAT1 C92/333/345/365/387/467/516/528/546A
homotetramer
-
HisACAT1
additional information
-
SDS-PAGE: detection of two protein bands with apparent sizes at 50 and 56 kDa, immunoblots: existence of 100 and 200 kDa bands, clarification of these observations needed
additional information
-
deleting a dimer-forming motif from the full-length ACAT1 converts the enzyme from a homotetramer to a homodimer that is more catalytically active than the native homotetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
Q61263
two potential N-glycosylation sites close to the C-terminal end of the polypeptide identified
glycoprotein
-
two potential N-glycosylation motifs at N329 and N387, only the second of which is present in the human enzyme
glycoprotein
-
-
glycoprotein
-
two potential N-glycosylation sites close to the C-terminal end of the polypeptide identified
glycoprotein
P53629
there are six potential N-linked glycosylation sites in sat1, two of which are conserved in sat2
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
-
apparent t1/2 of activity loss: approximately 12 min for HisACAT1 and 20 min for the mutant HisACAT1/1-65, for the mutant HisACAT1/P64 the heat inactivation curve falls between the curves for HisACAT1 and HisACAT/1-65 and its shape seems to be biphasic
486710
80
-
10 min, complete loss of activity
486685
100
-
liver enzyme, 10 min, activity destroyed
486677
additional information
-
the enzyme activity in Chinese hamster cells is more thermolabile than the enzyme activity in human cells
486695
additional information
-
enzyme activity expressed in Sf9 insect cells exhibits heat stability comparable of that of human enzyme, its heat stability is significantly greater than that of hamster enzyme
486697
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the use of organic solvents or strong detergents for the suspension of cholesterol must be avoided because of their affect on the enzyme
additional information
Rattus norvegicus male Sprague-Dawley
-
the use of organic solvents or strong detergents for the suspension of cholesterol must be avoided because of their affect on the enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-40C, stable for several weeks
-
-80C, stable for several weeks
-
-70C, biopsies, potassium phosphate buffer, stable for at least 3 years
-
-70C, microsomal preparations, stable for up to 1.5 years
-
-70C, liver microsomal enzyme, stable for several months
-
-80C, stable for several weeks
-
frozen, stable for up to 2 weeks
-
ovary, labile to freezing
-
-80C, stable for several weeks
-
-70C, liver microsomal enzyme, stable for several months
-
4C, Tris buffer, 1 mM EDTA, pH 7.7, 6.0 mg/ml protein, 5.0 mg/ml cholate, 5.5 mg/ml deoxycholate, 0.5 M potassium chloride, solubilized enzyme, stable for at least 18 h
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
microsomes from AC29 cells are prepared
-
microsomes from AC29 cells are prepared
-
microsomes are prepared
-
microsomal fractions are prepared
-
microsomal fractions of CHO cells are prepared
-
microsomal fractions of Hi5 cells containing baculovirally expressed hACAT-1 are prepared and used as the source for the enzyme; microsomal fractions of Hi5 cells containing baculovirally expressed hACAT-2 are prepared and used as the source for the enzyme
-
microsomal fractions of Hi5 cells containing baculovirally expressed hACAT-1 are used as sources of the enzyme; microsomal fractions of Hi5 cells containing baculovirally expressed hACAT-2 are used as sources of the enzyme
-
microsomes are prepared
-
microsomes prepared from monocyte-derived macrophagesare are used as an enzyme source
-
of the glutathione S-transferase-ACAT1 peptide fusion protein using chromatography on glutathione-Sepharose 4B column and of various recombinant HisACAT1s expressed in infected H5 cells using a Talon Superflow resin
-
of the recombinant enzyme using solubilization with CHAPS und KCl, chromatography on cobalt column and chromatography on monoclonal antibody affinity column
-
microsomes are prepared
-
liver microsomes are prepared
-
microsomal fractions are prepared
-
microsomes are prepared
-
based on solubilization in CHAPS, preparative free-flow isotachophoresis, and further separation of the protein showing enzyme activity by preparative free-flow IEF, followed by removal of nonglycosylated proteins by ConA-affinity chromatography and preparative SDS-PAGE
-
partial, using ammonium acetate fractionation and Sepharose 4B column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
all constructs, full-length, chimeras and mutants are cloned into the pCDNA3 vector, AC29 cells are transfected
-
expression of isoforms ACAT1 and ACAT2 in CHO cell; expression of isoforms ACAT1 and ACAT2 in CHO cell
-
expression of isoforms ACAT1 and ACAT2 in CHO cells; expression of isoforms ACAT1 and ACAT2 in CHO cells
-
expression of isoforms ACT1 and ACAT2 in CHO cell; expression of isoforms ACT1 and ACAT2 in CHO cell
-
cDNA cloned
-
a recombinant baculovirus transfer vector is constructed by subcloning of human ACAT-1 cDNA into pFASTBacHis; a recombinant baculovirus transfer vector is constructed by subcloning of human ACAT-2 cDNA into pFASTBacHis
-
a stable cell line expressing hACAT-1 from AC-29 cells is established; a stable cell line expressing hACAT-2 from AC-29 cells is established
-
CHO cells stably overexpressing human ACAT-1 are used; CHO cells stably overexpressing human ACAT-2 are used
-
expressed as a His-tagged fusion protein in Escherichia coli; expressed as a His-tagged fusion protein in Escherichia coli
-
expression in enzyme-deficient mutant chinese hamster ovary cells
-
expression in enzyme-deficient mutant chinese hamster ovary cells; expression in insect SF9 cells
-
expression in enzyme-deficient mutant chinese hamster ovary cells; expression of an antisense cDNA in HepG2 cells; sequence analysis and human cDNA clones indicate homology to liver carboxylesterase
-
expression in insect SF9 cells
-
expression in sat1 sat2 mutant cells of Saccharomyces cerevisiae
-
expression of ACAT1 in infected insect High Five cells
-
mutants generated by baculovirus expression technology; mutants generated by baculovirus expression technology
-
production of glutathione S-transferase-ACAT1 fusion proteins, expression of fusion proteins in Escherichia coli and expression of various recombinant HisACAT1s in infected H5 cells
-
recombinant hACAT1 (HisACAT1/Flag) is expressed in HEK293 cells
-
recombinant hACAT1 expressed in CHO cells
-
the baculovirus system is used
-
using the baculovirus system
-
expression in enzyme-deficient mutant chinese hamster ovary cells
Q61263
expression in Xenopus oocytes
-
expression in AC29 cells
-
presence of two gene products: ACAT1 and ACAT2, the gene product ACAT2 cloned from an African green monkey liver cDNA library. Transfection of the cloned ACAT2 cDNA into two different mammalian cell types
-
expression in human embryonic kidney A293 cells and expression in Chinese hamster ovary cells
-
two genes, SAT1 and SAT2 encode isozymes of the enzyme
P53629
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
extracellular signal-regulated kinase inhibitor PD98059, p38 mitogen-activated protein kinase inhibitor SB203580, or c-Jun N-terminal kinase inhibitor SP600125 down-regulate the expression of ACAT1 in a dose-dependent manner
-
no effect from androgen treatment on ACAT1 protein expression in LNCaP cells nor from treatment on ACAT2 expression in PC-3 cells
-
ACAT2 expression is induced upon androgen agonist R1881 treatment of LNCaP cells. Increase in the in vitro ACAT1 activity in PC-3 cells treated with androgen
-
angiotensin II significantly increases ACAT1 protein expression in a time- or concentration-dependent manner. Application of angiotensin II type 1 receptor agonist L162313, but not angiotensin II type 2 receptor agonist CGP42112A, mimicks the effects of angiotensin II treatment in inducing ACAT1 protein expression. ACAT activity and ACAT1 mRNA levels are also significantly increased by angiotensin II. Two-fold increases in ACAT1 protein expression and ACAT activity with angiotensin II treatment are completely inhibited by angiotensin type I receptor antagonists candesartan, [Sar(1),Ile(8)]-angiotensin II
-
in PC-3 cells treated with androgen agonist R1881, ACAT1 protein expression and cholesterol ester levels are decreased
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A1:1-123
-
chimeric protein A1(1-123)-A2(105-526)
A1:1-385
-
chimeric protein A1(1-385)-A2(364-440)-A1(463-550)
A1:1-71
-
chimeric protein A1(1-71)-A2(70-562)
A1D400N
-
mutant, evaluation of conserved aspartic acid residues
A1D406A
-
mutant, evaluation of conserved aspartic acid residues
A1H386N
-
mutant, identification of essential histidines required for activity
A1H425A
-
mutant, identification of essential histidines required for activity
A1H460A
-
mutant, identification of essential histidines required for activity
A1S128A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S194A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S269A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S410A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S412A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S414L
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1S456A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A1Y142F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y308F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y312F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y322F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y404F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y433F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A1Y518F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2:1-227
-
chimeric protein A2(1-227)-A1(248-489)-A2(468-526)
A2:1-249
-
chimeric protein A2(1-249)-A1(270-362)-A2(341-526)
A2:1-363
-
chimeric protein A2(1-363)-A1(386-462)-A2(441-526)
A2:1-428
-
chimeric protein A2(1-428)-A1(444-550)
A2:1-440
-
chimeric protein A2(1-440)-A1(463-502)-A2(480-526)
A2:1-479
-
chimeric protein A2(1-479)-A1(502-550)
A2C497S
-
A2 mutant
A2I491V
-
A2 mutant
A2L480M
-
A2 mutant
A2L495F
-
A2 mutant
A2M484S
-
A2 mutant
A2Q489N
-
A2 mutant
A2Q492L
-
A2 mutant
A2R504Q
-
A2 mutant
A2S494C
-
A2 mutant
A2V493L
-
A2 mutant
Ch1
-
chimeric protein A2(1-428)-A1(451-462)-A2(441-526)
CT504
-
A2(1-504)
A2D378E
-
mutant, evaluation of conserved aspartic acid residues
A2D384A
-
mutant, evaluation of conserved aspartic acid residues
A2H364N
-
mutant, identification of essential histidines required for activity
A2H403A
-
mutant, identification of essential histidines required for activity
A2H438A
-
mutant, identification of essential histidines required for activity
A2S109A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S176A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S249A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S388A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S390A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S392A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2S434A
-
mutant, identification of the role of conserved serine residues in determination of the activity
A2Y124F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y286F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y290F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y300F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y382F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y411F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
A2Y496F
-
mutant, evaluation of the role of conserved tyrosine residues as a requirement for the activity
C333A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-333 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C333A/C345A/C365A
-
expressed in H5 cells, the mutant contains essentially the same activity as the wild-type ACAT1. Sensitive to p-chloromercuribenzene sulfonic acid inhibition
C345A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-345 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C345A/C467A
-
insensitive to p-chloromercuribenzene sulfonic acid
C365A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-365 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C387A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-387 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C467A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-467 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C516A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-516 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C528A
-
expressed in H5 cells, the mutant retains a significant amount of activity, Cys-528 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C546A
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expressed in H5 cells, the mutant retains a significant amount of activity , Cys-546 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C92A
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expressed in H5 cells, the mutant retains a significant amount of activity, Cys-92 is not essential for ACAT1 catalysis, the mutant is expressed as a single, undegraded 50-kDA band
C92A/C333A/C345A/C365A/C387A/C467A/C516A
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resistant to p-chloromercuribenzene sulfonic acid inhibition
C92A/C333A/C345A/C365A/C387A/C467A/C516A/C528A/C54
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expressed in H5 cells or in ACAT-deficient Chinese hamster ovary cells: both mutants retain partial enzyme activity, this mutant is localized in endoplasmic reticulum in Chinese hamster ovary cells, homotetramer. Insensitive to p-chloromercuribenzene sulfonic acid
C92A/C333A/C345A/C365A/C387A/C467A/C516A/C546A
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this mutant is localized in endoplasmic reticulum in Chinese hamster ovary cells, expressed in H5 cells or in ACAT-deficient Chinese hamster ovary cells: both mutants retain partial enzyme activity. Resistant to p-chloromercuribenzene sulfonic acid inhibition
C92A/C333A/C345A/C365A/C387A/C516A/C528A/C546A
-
sensitive to p-chloromercuribenzene sulfonic acid inhibition
C92A/C333A/C345A/C365A/C467A/C516A/C546A
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expressed in H5 cells or in ACAT-deficient Chinese hamster ovary cells: both mutants retain partial enzyme activity. Resistant to p-chloromercuribenzene sulfonic acid inhibition
C92A/C333A/C365A/C387A/C467A/C516A/C528A/C546A
-
insensitive to p-chloromercuribenzene sulfonic acid
C92A/C467A/C516A/C546A
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expressed in H5 cells or in ACAT-deficient Chinese hamster ovary cells: both mutants retain partial enzyme activity, this mutant is localized in endoplasmic reticulum in Chinese hamster ovary cells
H360A
-
complete loss of activity
H386A
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complete loss of activity. Enzymatic activity is restored to values below 37% of the level of the wild-type activity when cholesterol is replaced by 25-hydroxycholesterol as substrate
H399A
-
complete loss of activity
H425A
-
59% of the wild-type activity, inhibitory sensitivity against oleic acid anilide ias decreased about 3fold
H434A
-
almost complete loss of activity
H434N
-
almost complete loss of activity
H460A
-
complete loss of activity
H501A
-
75% of the wild-type activity, inhibitory sensitivity against oleic acid anilide ias decreased about 10fold
S245A
-
no loss of activity
S245L
-
about 40% loss of activity
H527A
-
96% of the wild-type activity, inhibitory sensitivity against oleic acid anilide ias decreased about 10fold
additional information
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production of double or single proline mutants derived from glutathione S-transferase-ACAT1 fusion proteins shows that the dimer-forming domain is within ACAT1 amino acids 30 to 94. Production of mutants derived from the recombinant plasmid pHisACAT1 to test the effect of mutagenizing or deleting the N-terminal peptide on the oligomerization state of ACAT1
additional information
-
insertion of two different antigenic tags at various hydrophilic regions flanking each of the predicted transmembrane domains, analysis indicates that the enzyme contains only 2 detectable transmembrane domains, located near the N-terminal region
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
solubilization of enzyme activity by deoxycholate, reconstitution of the solubilized activity into liposome of known cholesterol and phospholipid content by employing a cholate dialysis procedure
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solubilization of the cell extracts with deoxycholate followed by dilution into preformed liposomes
-
solubilization of the cell extracts with deoxycholate followed by dilution into preformed liposomes
-
solubilization of enzyme activity from Ehrlich ascites cells, the solubilized activity can be reconstituted as a liposome complex after the detergent is removed
-
the enzyme must be reconstituted into an artificial membrane for optimal activity
-
reconstitution with liposomes
-
solubilization of enzyme activity by deoxycholate, reconstitution of the solubilized activity into liposome of known cholesterol and phospholipid content by employing a cholate dialysis procedure
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
identified as a major target for inhibition, based on the hypothesis that enzyme inhibitors may have a direct antiatherosclerotic effect within the arterial wall and a direct effect in blocking cholesterol absorption in the small intestine, and in reducing very-low-density lipoprotein secretion in the hepatocytes
medicine
-
for both isoform ACTA1 and ACAT2, overexpression in rat hepatoma McA-RH7777 cells results in increased synthesis, cellular accumulation, and secretion of cholesteryl esters. This leads to decreased intracellular degradation and increased secretion of very low density liporotein apoB. Overexpression of ACAT2 has significantly greater impact upon assembly and secretion of very low density liporotein from liver cells than that of ACAT1
medicine
-
elevated ACAT2expression may serve as a new biomarker for certain forms of hepatocellular carcinoma
medicine
-
systemic ACAT inhibition reduces circulating tumor necrosis factor-alpha levels in hypercholesterolemic subjects and improves resistance-vessel endothelial function, with small effects on circulating cholesterol. This may be a novel therapeutic strategy to target vascular inflammation and endothelial dysfunction in atherosclerosis
medicine
-
an anti-oxidative ACAT inhibitor or the combination of an antioxidant and an ACAT inhibitor protects foam cells from oxidative stress and effectively reduces cholesterol levels, which would be a promising approach in anti-atherosclerotic therapy
medicine
-
statin treatment reduces ACAT2 activity in human liver and this effect, in combination with a reduced ApoE expression, may contribute to the favorable lowering of VLDL cholesterol seen in addition to the LDL lowering during statin treatment
medicine
-
the study provides evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis
pharmacology
-
ACAT-1 and ACAT-2 selective inhibitors may prove to have clinical benefit to reduce atherosclerosis via directly reducing the size of the lipid-rich core in the atherosclerotic plaques or the absorption of cholesterol in intestine, respectively
pharmacology
-
K-604, a potent and selective inhibitor of ACAT-1, suppresses the development of atherosclerosis in an animal model without affecting plasma cholesterol levels, providing direct evidence that pharmacological inhibition of ACAT-1 in the arterial walls leads to suppression of atherosclerosis
pharmacology
-
the data suggest that antiatherosclerotic activity of licorice in hypercholesterolemic patients might be related with its ACAT inhibitory effects
medicine
-
ACAT is a key enzyme in controlling cholesterol metabolism and represents a promising target for the development of therapeutic agents and inhibitors to control hypercholesterolemia, atherosclerosis and Alzheimer's disease
medicine
-
the results suggest that the ACAT inhibitor VULM 1457 is a prospective hypolipidemic and anti-atherogenic drug which treats diabetes
medicine
-
feeding a diet suplemented with linoleic acid, conjugated linoleic acid, alpha-linolenic acid or conjugated linolenic acid results in decrease in plasma cholesterol, with conjugated linoleic acid being the most effective. Diets have no effect on sterol regulatory element binding protein-2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7-hydroxylase. The four octadecaenoic acids increase the excretion of fecal neutral sterols with conjugated linoleic acid being most effective followed by alphga-linolenic acid, linoleic acid and conjugated linolenic acid. Dietary conjugated linoleic acid is associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase activity followed by alpha-linolenic acid, linoleic acid and conjugated linolenic acid in a decreasing trend
nutrition
-
increase in enzyme activity in animals fed with palmitic acid. No difference in hepatic enzyme activity in animals fed with oleic acid or linoleic acid
nutrition
-
feeding a diet suplemented with linoleic acid, conjugated linoleic acid, alpha-linolenic acid or conjugated linolenic acid results in decrease in plasma cholesterol, with conjugated linoleic acid being the most effective. Diets have no effect on sterol regulatory element binding protein-2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7-hydroxylase. The four octadecaenoic acids increase the excretion of fecal neutral sterols with conjugated linoleic acid being most effective followed by alphga-linolenic acid, linoleic acid and conjugated linolenic acid. Dietary conjugated linoleic acid is associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase activity followed by alpha-linolenic acid, linoleic acid and conjugated linolenic acid in a decreasing trend
medicine
-
inbred strains with high/low response in low-density lipoprotein cholesterol to dietary cholesterol and fat, resp. High responding animals have significantly higher percent cholesterol absorption, hepatic free and esterified cholesterol, and hepatic enzyme activity than low responding animals on high cholesterol and high fat diet. Hepatic enzyme activity, but not the intestinal activity is associated with hepatic cholesterol concentration and percent cholesterol absorption
analysis
-
use of inhibitor K-604, selective for isoform ACAT-1, to measure the individual enzymatic activities of isoforms ACAT-1 and ACAT-2 in semniferous tubule
medicine
O88908
hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins, and therapeutic interventions, such as the ACAT2-specific antisense oligonucleotide used here, which reduce acyltransferase 2 (ACAT2) function in the liver without affecting ACAT1, may provide clinical benefit for cardiovascular disease prevention
medicine
-
the study provides evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis
pharmacology
-
the results strongly support the idea that CS-505 could be promising as a therapeutic agent for the treatment of atherosclerosis
medicine
-
the results suggest that this novel hypolipidaemic agent exert antiarrhythmic and infarct size-limiting effects in the diabetic-hypercholesterolaemic rat heart
pharmacology
-
the data suggest that antiatherosclerotic activity of licorice in hypercholesterolemic patients might be related with its ACAT inhibitory effects