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