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Literature summary for 2.3.1.26 extracted from

  • Rogers, M.A.; Liu, J.; Song, B.L.; Li, B.L.; Chang, C.C.; Chang, T.Y.
    Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): enzymes with multiple sterols as substrates and as activators (2015), J. Steroid Biochem. Mol. Biol., 151, 102-107.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
ent-cholesterol
-
Homo sapiens
ent-cholesterol
-
Mus musculus
epi-cholesterol
-
Homo sapiens
epi-cholesterol
-
Mus musculus
additional information enzyme ACAT1 can be activated by a variety of sterols. All sterols that possess the iso-octyl side chain including cholesterol, oxysterols, various plant sterols can all be activators of ACAT. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates Homo sapiens
additional information enzyme ACAT1 can be activated by a variety of sterols. All sterols that possess the iso-octyl side chain including cholesterol, oxysterols, various plant sterols can all be activators of ACAT. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates Mus musculus
additional information enzyme ACAT1 can be activated by a variety of sterols. All sterols that possess the iso-octyl side chain including cholesterol, oxysterols, various plant sterols can all be activators of ACAT. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates. When pregnenolone and cholesterol (or other sterol analogues) are both present, binding of cholesterol at site A causes conformational changes, enabling the enzyme to increase the rate of esterification reaction much more efficiently Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene ACAT1, human Acat1 is located in two different chromosomes, chromosomes 1 and 7, with each site containing a distinct promoter: chromosome 1 contains exons 1-16, and chromosome 7 contains the optional long exon Xa, recombinant expression, functional complementation of a Chinese hamster ovary cell mutant lacking ACAT activity, the majority of ACAT1 mRNAs is transcribed from exons 1-16 Homo sapiens
gene ACAT1, in mouse the Acat1 gene is located solely on chromosome 1 and contains 17 exons Mus musculus
gene ACAT2, human gene Acat2 is located in chromosome 12 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information ACAT1 is an allosteric enzyme, modeling, overview Mus musculus
additional information
-
additional information ACAT1 is an allosteric enzyme, modeling, overview. When assayed in reconstituted liposomes or in mixed micelles, the purified recombinant enzyme responds to cholesterol as its substrate in a sigmoidal manner, kinetic analysis Homo sapiens
additional information
-
additional information ACAT2 is an allosteric enzyme, modeling, overview Mus musculus
additional information
-
additional information ACAT2 is an allosteric enzyme, modeling, overview. The enzyme responds to cholesterol as its substrate in a sigmoidal manner, kinetic analysis Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum ACAT1 is a resident enzyme at the endoplasmic reticulum Homo sapiens 5783
-
endoplasmic reticulum ACAT1 is a resident enzyme at the endoplasmic reticulum Mus musculus 5783
-
additional information ACAT1 is in a position to esterify cholesterol and various cholesterol metabolites (i.e., oxysterols, pregnenolone etc.) traversing through the mitochondria and endoplasmic reticulum membranes Homo sapiens
-
-
additional information ACAT1 is in a position to esterify cholesterol and various cholesterol metabolites (i.e., oxysterols, pregnenolone etc.) traversing through the mitochondria and endoplasmic reticulum membranes Mus musculus
-
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
48000
-
x * 48000, SDS-PAGE Homo sapiens
50000
-
4 * 50000, enzyme protein transcribed from exons 1-16, SDS-PAGE, 4 * 56000, second enzyme variant from chromosome 7, SDS-PAGE, ACAT1 may act as a dimer of dimer Homo sapiens
50000
-
4 * 50000, SDS-PAGE, ACAT1 may act as a dimer of dimer Mus musculus
56000
-
4 * 50000, enzyme protein transcribed from exons 1-16, SDS-PAGE, 4 * 56000, second enzyme variant from chromosome 7, SDS-PAGE, ACAT1 may act as a dimer of dimer Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the enzyme contains two different binding sites for steroidal molecules. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including pregnenolone, oxysterols such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc., and various plant sterols, can all be ACAT substrates. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates ?
-
?
additional information Mus musculus the enzyme contains two different binding sites for steroidal molecules. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including pregnenolone, oxysterols such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc., and various plant sterols, can all be ACAT substrates. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O75908 SOAT2 or ACAT2
-
Homo sapiens P35610 SOAT1 or ACAT1
-
Mus musculus O88908 SOAT2 or ACAT2
-
Mus musculus Q61263 SOAT1 or ACAT1
-

Purification (Commentary)

Purification (Comment) Organism
recombinant 50-kDa human ACAT1 to homogeneity with full retention in enzymatic activity Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
adrenal gland
-
Homo sapiens
-
brain ACAT1 expression Mus musculus
-
hepatocyte
-
Homo sapiens
-
hepatocyte
-
Mus musculus
-
intestine
-
Homo sapiens
-
intestine
-
Mus musculus
-
JURKAT cell
-
Homo sapiens
-
lymphoma cell
-
Homo sapiens
-
additional information ACAT1 is ubiquitously expressed in essentially all tissues examined Homo sapiens
-
additional information ACAT1 is ubiquitously expressed in essentially all tissues examined Mus musculus
-
additional information ACAT2 is mainly expressed in the intestines and hepatocytes. It is also expressed in various other tissues, but at much lower levels than ACAT1 Homo sapiens
-
additional information ACAT2 is mainly expressed in the intestines and hepatocytes. It is also expressed in various other tissues, but at much lower levels than ACAT1 Mus musculus
-
neuroblastoma cell
-
Homo sapiens
-
SH-SY5Y cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acyl-CoA + 24(S)-hydroxycholesterol
-
Homo sapiens CoA + acyl (24S)-24-hydroxycholesterol
-
?
acyl-CoA + cholesterol cholesterol is the preferred acceptor substrate Homo sapiens CoA + cholesterol ester
-
?
acyl-CoA + cholesterol cholesterol is the preferred acceptor substrate Mus musculus CoA + cholesterol ester
-
?
acyl-CoA + cholesterol cholesterol is the preferred acceptor substrate, and for ACAT1, the preferred fatty acyl-CoA is oleoyl coenzyme A Homo sapiens CoA + cholesterol ester
-
?
acyl-CoA + cholesterol cholesterol is the preferred acceptor substrate, and for ACAT1, the preferred fatty acyl-CoA is oleoyl coenzyme A Mus musculus CoA + cholesterol ester
-
?
acyl-CoA + pregnenolone
-
Homo sapiens CoA + pregnenolyl 3-O-acyl ester
-
?
acyl-CoA + pregnenolone
-
Mus musculus CoA + pregnenolyl 3-O-acyl ester
-
?
additional information the enzyme contains two different binding sites for steroidal molecules. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including pregnenolone, oxysterols such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc., and various plant sterols, can all be ACAT substrates. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates Homo sapiens ?
-
?
additional information the enzyme contains two different binding sites for steroidal molecules. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including pregnenolone, oxysterols such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc., and various plant sterols, can all be ACAT substrates. Pregnenolone can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates Mus musculus ?
-
?
additional information when assayed in reconstituted liposomes or in mixed micelles, the purified recombinant enzyme responds to cholesterol as its substrate in a sigmoidal manner. When pregnenolone and cholesterol (or other sterol analogues) are both present, binding of cholesterol at site A causes conformational changes, enabling the enzyme to increase the rate of esterification reaction much more efficiently Homo sapiens ?
-
?
oleoyl-CoA + cholesterol cholesterol is the preferred acceptor substrate, and for ACAT1, the preferred fatty acyl-CoA is oleoyl coenzyme A Homo sapiens CoA + cholesteryl oleate
-
?
oleoyl-CoA + cholesterol cholesterol is the preferred acceptor substrate, and for ACAT1, the preferred fatty acyl-CoA is oleoyl coenzyme A Mus musculus CoA + cholesteryl oleate
-
?

Subunits

Subunits Comment Organism
? x * 48000, SDS-PAGE Homo sapiens
tetramer 4 * 50000, enzyme protein transcribed from exons 1-16, SDS-PAGE, 4 * 56000, second enzyme variant from chromosome 7, SDS-PAGE, ACAT1 may act as a dimer of dimer Homo sapiens
tetramer 4 * 50000, SDS-PAGE, ACAT1 may act as a dimer of dimer Mus musculus

Synonyms

Synonyms Comment Organism
ACAT
-
Homo sapiens
ACAT
-
Mus musculus
ACAT1
-
Homo sapiens
ACAT1
-
Mus musculus
ACAT2
-
Homo sapiens
ACAT2
-
Mus musculus
acyl-CoA:cholesterol acyltransferase
-
Homo sapiens
acyl-CoA:cholesterol acyltransferase
-
Mus musculus
SOAT
-
Homo sapiens
SOAT
-
Mus musculus
Soat1
-
Homo sapiens
Soat1
-
Mus musculus
Soat2
-
Homo sapiens
Soat2
-
Mus musculus

General Information

General Information Comment Organism
evolution along with acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), ACAT1 and ACAT2 are founding members of the membrane-bound O-acyltransferase (MBOAT) enzyme family. MBOATs are multispan membrane enzymes that use long-chain or medium-chain fatty acyl-CoA as the first substrate, and catalyze the transfer of the fatty acyl group to the 3beta-hydroxyl moiety of a certain hydrophobic substance as the second substrate. An MBOAT contains two active sites: a histidine within a long hydrophobic peptide region, and an asparagine located within a long hydrophilic peptide region Homo sapiens
evolution along with acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), ACAT1 and ACAT2 are founding members of the membrane-bound O-acyltransferase (MBOAT) enzyme family. MBOATs are multispan membrane enzymes that use long-chain or medium-chain fatty acyl-CoA as the first substrate, and catalyze the transfer of the fatty acyl group to the 3beta-hydroxyl moiety of a certain hydrophobic substance as the second substrate. An MBOAT contains two active sites: a histidine within a long hydrophobic peptide region, and an asparagine located within a long hydrophilic peptide region Mus musculus
malfunction blocking ACAT enzyme activity with ACAT inhibitors, or with genetic ablation of ACAT1, significantly increases macrophage apoptosis Homo sapiens
malfunction blocking ACAT enzyme activity with ACAT inhibitors, or with genetic ablation of ACAT1, significantly increases macrophage apoptosis Mus musculus
metabolism the enzyme converts cholesterol to cholesteryl esters and plays key roles in the regulation of cellular cholesterol homeostasis. It metabolizes diverse substrates including both sterols and certain steroids, and it contains two different binding sites for steroidal molecules Homo sapiens
metabolism the enzyme converts cholesterol to cholesteryl esters and plays key roles in the regulation of cellular cholesterol homeostasis. It metabolizes diverse substrates including both sterols and certain steroids, and it contains two different binding sites for steroidal molecules Mus musculus
physiological function a major function of ACATs is to protect against the unnecessary built up of free cholesterol within the cell membranes. ACAT1 may be involved in negatively regulating steroidogenesis in human adrenal cells. Both ACAT1 and ACAT2 can control the oxysterol levels by directly esterifying them, in a cell-type specific manner. ACAT can also control oxysterol levels by altering the cholesterol pool from which oxysterols are derived Homo sapiens
physiological function a major function of ACATs is to protect against the unnecessary built up of free cholesterol within the cell membranes. Both ACAT1 and ACAT2 can control the oxysterol levels by directly esterifying them, in a cell-type specific manner. ACAT can also control oxysterol levels by altering the cholesterol pool from which oxysterols are derived Mus musculus
physiological function a major function of ACATs is to protect against the unnecessary built up of free cholesterol within the cell membranes. In intestines, ACAT2 provides cholesteryl esters for lipoprotein assemblies. Both ACAT1 and ACAT2 can control the oxysterol levels by directly esterifying them, in a cell-type specific manner. ACAT can also control oxysterol levels by altering the cholesterol pool from which oxysterols are derived Homo sapiens
physiological function a major function of ACATs is to protect against the unnecessary built up of free cholesterol within the cell membranes. In intestines, ACAT2 provides cholesteryl esters for lipoprotein assemblies. Both ACAT1 and ACAT2 can control the oxysterol levels by directly esterifying them, in a cell-type specific manner. ACAT can also control oxysterol levels by altering the cholesterol pool from which oxysterols are derived Mus musculus