Page last updated: 2024-10-24

sterol O-acyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: acyl-CoA + a sterol = CoA + a sterol ester. [EC:2.3.1.26, GOC:mah]

Sterol O-acyltransferase activity is a crucial enzymatic process involved in the modification of sterols, particularly cholesterol, by attaching a fatty acid chain to the hydroxyl group at the 3-beta position. This process is catalyzed by a family of enzymes known as sterol O-acyltransferases (SOATs), also referred to as acyl-CoA:cholesterol acyltransferases (ACATs). The primary function of SOATs is to esterify cholesterol, converting it to cholesterol esters. This esterification plays a significant role in regulating intracellular cholesterol homeostasis and lipid metabolism.

SOATs are involved in several critical cellular processes:

- **Cholesterol Storage:** By converting free cholesterol into cholesterol esters, SOATs facilitate the storage of cholesterol within lipid droplets, effectively decreasing the levels of free cholesterol within the cell. This mechanism is crucial for preventing the accumulation of free cholesterol, which could potentially disrupt membrane fluidity and cellular function.

- **Lipid Transport:** Cholesterol esters are less soluble in water than free cholesterol, rendering them more suitable for transport within the bloodstream. This transportation is facilitated by lipoprotein particles, which are responsible for delivering cholesterol to various tissues.

- **Cholesterol Metabolism:** SOATs participate in the regulation of cholesterol synthesis and degradation pathways. By modulating cholesterol esterification, SOATs contribute to maintaining appropriate levels of cholesterol within the cell.

- **Cellular Signaling:** SOATs have been implicated in cellular signaling pathways, particularly those associated with cell growth and proliferation.

- **Atherosclerosis:** The activity of SOATs, particularly ACAT1, has been linked to the development of atherosclerosis. Increased levels of cholesterol esters in the bloodstream contribute to the formation of atherosclerotic plaques, which can narrow arteries and increase the risk of cardiovascular diseases.

The molecular mechanism underlying sterol O-acyltransferase activity involves the transfer of an acyl group from an acyl-CoA molecule to the hydroxyl group of a sterol molecule. This reaction is typically catalyzed by a two-step mechanism:

1. **Acyl-CoA Binding:** The enzyme first binds an acyl-CoA molecule, typically palmitoyl-CoA or oleoyl-CoA, in its active site.

2. **Sterol Binding:** Subsequently, the enzyme binds the sterol molecule, usually cholesterol, in close proximity to the acyl-CoA.

3. **Acyl Transfer:** The enzyme facilitates the transfer of the acyl group from the acyl-CoA to the 3-beta hydroxyl group of the sterol molecule, forming a cholesterol ester.

SOATs are critical enzymes with a wide range of functions, contributing to crucial cellular processes like cholesterol homeostasis, lipid metabolism, and cellular signaling. Their activity is tightly regulated to ensure proper cholesterol levels and prevent the development of cardiovascular diseases.'
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Proteins (2)

ProteinDefinitionTaxonomy
Sterol O-acyltransferase 1A sterol O-acyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35610]Homo sapiens (human)
Sterol O-acyltransferase 2A sterol O-acyltransferase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75908]Homo sapiens (human)

Compounds (32)

CompoundDefinitionClassesRoles
diethyl pyrocarbonatediethyl pyrocarbonate : The diethyl ester of dicarbonic acid.

Diethyl Pyrocarbonate: Preservative for wines, soft drinks, and fruit juices and a gentle esterifying agent.
acyclic carboxylic anhydride
procainamideprocainamide : A benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias.

Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.
benzamidesanti-arrhythmia drug;
platelet aggregation inhibitor;
sodium channel blocker
edrophonium chlorideedrophonium chloride : The chloride salt of edrophonium. A reversible inhibitor of cholinesterase with a rapid onset (30-60 seconds after injection) but a short duration of action (5-15 minutes), it is used in myasthenia gravis both diagnostically and to distinguish between under- or over-treatment with other anticholinesterases. It has also been used for the reversal of neuromuscular blockade in anaesthesia, and for the management of poisoning due to tetrodotoxin, a neuromuscular blocking toxin found in puffer fish and other marine animals.chloride salt;
quaternary ammonium salt
antidote;
diagnostic agent;
EC 3.1.1.8 (cholinesterase) inhibitor
territrem bterritrem B: tremorgenic mycotoxin from Aspergillus terreus; RN given refers to (4aR-(4aalpha,6abeta,12aalpha,12bbeta))-isomer
pd 128042PD 128042: structure given in first sourceanilide
cl 277082CL 277082: structure given in first source
1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone: an inhibitor of cholesterol absorption; structure given in first source
atractylenolide iiiatractylenolide III: from Atractylodes macrocephala Koidz; structure in first sourcenaphthofuranmetabolite
avasimibemonoterpenoid
22s-hydroxycholesterol(22S)-22-hydroxycholesterol : An oxysterol that is the 22S-hydroxy derivative of cholesterol.22-hydroxy steroid;
3beta-hydroxy-Delta(5)-steroid;
oxysterol
f 1394F 1394: an acyl-CoA:cholesterol acyltransferase (ACAT) inibitor; structure given in first source
oleic acidoleic acid : An octadec-9-enoic acid in which the double bond at C-9 has Z (cis) stereochemistry.

Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)
octadec-9-enoic acidantioxidant;
Daphnia galeata metabolite;
EC 3.1.1.1 (carboxylesterase) inhibitor;
Escherichia coli metabolite;
mouse metabolite;
plant metabolite;
solvent
beta-hydroxyisovalerylshikonin
shikoninshikonin: a naphthazarin; has antineoplastic and angiogenesis inhibiting activitieshydroxy-1,4-naphthoquinone
carbenoxolone
pactimibe
linoleic acidlinoleic acid : An octadecadienoic acid in which the two double bonds are at positions 9 and 12 and have Z (cis) stereochemistry.

Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
octadecadienoic acid;
omega-6 fatty acid
algal metabolite;
Daphnia galeata metabolite;
plant metabolite
oleylamidealiphatic amide : A carboxamide in which the amide linkage is bonded directly to an aliphatic system.

oleamide : A fatty amide derived from oleic acid.

oleylamide: plastic additive; can cause contact urticaria; RN given refers to (Z)-isomer; a sleep inducing factor
primary fatty amidehuman metabolite;
plant metabolite
muromonab-cd3cudraflavone B : An extended flavonoid that consists of a pyranochromane skeleton that is 2H,6H-pyrano[3,2-g]chromen-6-one substituted by geminal methyl groups at position 2, a 2,4-dihydroxyphenyl group at position 8, a hydroxy group at position 5 and a prenyl group at position 7. Isolated from Morus alba and Morus species it exhibits anti-inflammatory activity.

cudraflavone B: antiproliferative from Cudrania tricuspidata
extended flavonoid;
pyranochromane;
trihydroxyflavone
anti-inflammatory agent;
plant metabolite
macluraxanthone bmacluraxanthone B : A member of the class of xanthones that is 9H-xanthen-9-one substituted by hydroxy groups at positions 1, 3, 6 and 7, a dimethylallyl group at position 2 and a prenyl group at position 4. Isolated from Maclura tinctoria and Cudrania tricuspidata, it exhibits anti-HIV and antineoplastic activity.

macluraxanthone B: from the plant Maclura tinctoria; structure in first source
phenols;
xanthones
anti-HIV agent;
antineoplastic agent;
metabolite
oleoylanilideoleoylanilide: alters lipid metabolism of lung & adipose tissue; do not confuse with oleoanilide; RN given refers to (Z)-isomer

oleylanilide : The fatty amide resulting from the formal condensation of oleic acid and aniline.
anilide;
fatty amide
Pipercidebenzodioxoles
linoleamidelinoleamide : A fatty amide obtained from linoleic acid.

linoleamide: C18-H33-N-O
primary fatty amidehuman metabolite
manzamine amanzamine A : An alkaloid of the class of beta-carbolines isolated from Haliclona and Acanthostrongylophora. It exhibits inhibitory activity against Glycogen Synthase Kinase-3 (EC 2.7.11.26).

manzamine A: RN given refers to (1R-(1R*,9Z,13S*,13aR*,20aR*,21aR*)-isomer; RN for cpd without isomeric designation not avail 12/92
alkaloid;
beta-carbolines;
isoquinolines
animal metabolite;
anti-HSV-1 agent;
antimalarial;
antineoplastic agent;
EC 2.7.11.26 (tau-protein kinase) inhibitor;
marine metabolite
eflucimibeeflucimibe: a powerful and systemic acylcoenzyme A: cholesterol acyltransferase inhibitor
arisugacinarisugacin A : An organic heterotetracyclic compound that is 4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-4a,6,6a,12,12a,12b-hexahydro-4H,11H-benzo[f]pyrano[4,3-b]chromene-1,11(5H)-dione substituted by 3,4-dimethoxyphenyl group at position 9 (the 4aR,6aR,12aS,12bS steroisomer). Isolated from the culture broth of Penicillium, it acts as a selective inhibitor of acetylcholinesterase.

arisugacin: isolated from Penicillium sp. FO-4259; structure given in first source
aromatic ether;
delta-lactone;
enone;
organic heterotetracyclic compound;
tertiary alcohol
antimicrobial agent;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
metabolite;
Penicillium metabolite
manassantin bmanassantin B : A lignan isolated from Saururus cernuus and Saururus chinensis and has been shown to exhibit antineoplastic activity.

manassantin B: isolated from the roots of Saururus chinensis; structure in first source
benzodioxoles;
dimethoxybenzene;
lignan;
oxolanes;
secondary alcohol
antineoplastic agent;
metabolite
cudraxanthone lcudraxanthone L: from the root bark of Cudrania tricuspidata; structure in first source
pyripyropene apyripyropene A : A sesquiterpenoid that consists of (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-(acetoxymethyl)-12-hydroxy-4,6a,12b-trimethyl-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-diol in which the hydrogens of the 3- and 6-hydroxy functions are substituted by acetyl groups.

pyripyropene A: from Aspergillus fumigatus FO-1289; structure given in first source
organic heterotetracyclic compound;
sesquiterpenoid
acyl-CoA:cholesterol acyltransferase 2 inhibitor;
metabolite
cudraflavanone acudraflavanone A: antineoplastic from Cudrania tricuspidata; structure in first source
azd7687AZD7687: structure in first source
manassantin amanassantin A : A lignan isolated from Saururus cernuus and Saururus chinensis and has been shown to exhibit antineoplastic activity.

manassantin A: a dineolignan from Saururus cernuus; structure in first source