Page last updated: 2024-10-24

cholesterol efflux

Definition

Target type: biologicalprocess

The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle. [GOC:sart]

Cholesterol efflux is a critical process that removes excess cholesterol from cells, preventing its accumulation and the development of atherosclerosis. The process involves a series of steps mediated by specific proteins and involves the coordinated action of different cell types:

1. **Cellular Cholesterol Mobilization:** Cholesterol is mobilized from intracellular compartments like the endoplasmic reticulum and lysosomes, where it is stored. This step involves proteins like ATP-binding cassette transporter A1 (ABCA1) and ABCA7, which bind to cholesterol and facilitate its movement to the cell membrane.

2. **Cholesterol Transport to Acceptor Molecules:** Once at the cell membrane, cholesterol is transferred to acceptor molecules in the extracellular environment.
* **High-density lipoproteins (HDL):** HDL particles are the primary acceptors of cholesterol from cells. They are synthesized in the liver and have a structure that allows them to bind and transport cholesterol. ABCA1 is crucial for the transfer of cholesterol to HDL, forming nascent HDL particles.
* **Other Acceptors:** Other acceptors include scavenger receptor BI (SR-BI), which can directly take up cholesterol from cells, and various lipoproteins that can exchange cholesterol with HDL.

3. **Reverse Cholesterol Transport:** HDL particles with acquired cholesterol travel back to the liver through the bloodstream. This process is known as reverse cholesterol transport.
* **Cholesterol Esters:** In the plasma, cholesterol is converted to cholesterol esters by the enzyme lecithin-cholesterol acyltransferase (LCAT), making it more stable and allowing HDL to carry more cholesterol.
* **Delivery to Liver:** HDL particles deliver their cholesterol load to the liver, either directly or through exchange with other lipoproteins. The liver then processes the cholesterol and either uses it for biosynthesis or excretes it in bile.

4. **Cellular Cholesterol Homeostasis:** By removing excess cholesterol from cells, cholesterol efflux helps maintain cellular cholesterol homeostasis and prevent the buildup of cholesterol in the cell membrane and other compartments. This is essential for normal cell function and prevents the development of atherosclerosis.

This complex and well-regulated process plays a vital role in protecting against cardiovascular disease by removing excess cholesterol from cells and preventing its buildup in the arteries.'
"

Proteins (5)

ProteinDefinitionTaxonomy
Scavenger receptor class B member 1A scavenger receptor class B member 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8WTV0]Homo sapiens (human)
Lysosomal acid lipase/cholesteryl ester hydrolaseA lysosomal acid lipase/cholesteryl ester hydrolase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P38571]Homo sapiens (human)
Sterol O-acyltransferase 1A sterol O-acyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35610]Homo sapiens (human)
Catechol O-methyltransferaseA catechol O-methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P21964]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 (42)

CompoundDefinitionClassesRoles
oxyquinolineOxyquinoline: An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radio-indium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics.

quinolin-8-ol : A monohydroxyquinoline that is quinoline substituted by a hydroxy group at position 8. Its fungicidal properties are used for the control of grey mould on vines and tomatoes.
monohydroxyquinolineantibacterial agent;
antifungal agrochemical;
antiseptic drug;
iron chelator
verapamil2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile : A tertiary amino compound that is 3,4-dimethoxyphenylethylamine in which the hydrogens attached to the nitrogen are replaced by a methyl group and a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group.

verapamil : A racemate comprising equimolar amounts of dexverapamil and (S)-verapamil. An L-type calcium channel blocker of the phenylalkylamine class, it is used (particularly as the hydrochloride salt) in the treatment of hypertension, angina pectoris and cardiac arrhythmia, and as a preventive medication for migraine.

Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.
aromatic ether;
nitrile;
polyether;
tertiary amino compound
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
8-hydroxyquinoline-5-sulfonic acid8-hydroxyquinoline-5-sulfonic acid: RN given refers to parent cpd
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
rimcazolerimcazole: RN given refers to (cis)-isomer; structure given in first sourcecarbazoles
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
5'-methylthioadenosine5'-methylthioadenosine: structure

5'-S-methyl-5'-thioadenosine : Adenosine with the hydroxy group at C-5' substituted with a methylthio (methylsulfanyl) group.
thioadenosinealgal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
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
sitagliptinsitagliptin : A triazolopyrazine that exhibits hypoglycemic activity.triazolopyrazine;
trifluorobenzene
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
environmental contaminant;
hypoglycemic agent;
serine proteinase inhibitor;
xenobiotic
tolcaponetolcapone : Benzophenone substituted on one of the phenyl rings at C-3 and C-4 by hydroxy groups and at C-5 by a nitro group, and on the other phenyl ring by a methyl group at C-4. It is an inhibitor of catechol O-methyltransferase.

Tolcapone: A benzophenone and nitrophenol compound that acts as an inhibitor of CATECHOL O-METHYLTRANSFERASE, an enzyme involved in the metabolism of DOPAMINE and LEVODOPA. It is used in the treatment of PARKINSON DISEASE in patients for whom levodopa is ineffective or contraindicated.
2-nitrophenols;
benzophenones;
catechols
antiparkinson drug;
EC 2.1.1.6 (catechol O-methyltransferase) inhibitor
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
entacaponeentacapone : A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5-nitrophenyl group.

entacapone: structure given in first source
2-nitrophenols;
catechols;
monocarboxylic acid amide;
nitrile
antidyskinesia agent;
antiparkinson drug;
central nervous system drug;
EC 2.1.1.6 (catechol O-methyltransferase) inhibitor
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
lalistat 2
opicaponeopicapone: structure in first sourceoxadiazole;
ring assembly