Page last updated: 2024-10-24

regulation of cholesterol efflux

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of cholesterol efflux. Cholesterol efflux is the directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle. [GOC:BHF, GOC:dph, GOC:tb]

Cholesterol efflux is a critical process for maintaining cellular cholesterol homeostasis and preventing the accumulation of excess cholesterol in cells, which can lead to the development of atherosclerosis. This complex process involves the coordinated action of various proteins and enzymes that facilitate the removal of cholesterol from cells and its transport to other tissues for excretion.

The first step in cholesterol efflux is the mobilization of cholesterol from intracellular stores, primarily the plasma membrane and intracellular lipid droplets. This is achieved through the action of specific cholesterol transporters, such as ABCA1 and ABCG1, which are located in the cell membrane.

ABCA1 is a major player in cholesterol efflux, responsible for transporting cholesterol from cells to lipid-poor apolipoprotein A-I (apoA-I) to form nascent high-density lipoprotein (HDL). This process is ATP-dependent and involves the flipping of cholesterol from the inner leaflet of the cell membrane to the outer leaflet, where it can be picked up by apoA-I. ABCG1, another important transporter, facilitates the efflux of cholesterol from intracellular lipid droplets to nascent HDL particles.

Once cholesterol is bound to apoA-I, it is transported to the liver, where it is either metabolized or excreted in bile. This process of reverse cholesterol transport plays a crucial role in removing excess cholesterol from peripheral tissues and preventing atherosclerosis.

Several other factors influence cholesterol efflux, including the availability of apoA-I, the activity of enzymes like lecithin:cholesterol acyltransferase (LCAT), and the presence of various regulatory proteins.

LCAT is an enzyme responsible for esterifying cholesterol in HDL particles, which enhances their stability and promotes the transfer of cholesterol to other lipoproteins.

A variety of regulatory proteins, including the nuclear receptor LXRα, are involved in regulating cholesterol efflux. LXRα is activated by oxysterols and can bind to specific DNA sequences to induce the transcription of genes involved in cholesterol efflux, including ABCA1 and ABCG1.

Overall, cholesterol efflux is a complex and tightly regulated process involving multiple steps and factors. This process is essential for maintaining cholesterol homeostasis and preventing the development of atherosclerosis. Dysregulation of cholesterol efflux can lead to accumulation of cholesterol in cells, contributing to cardiovascular disease.'
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Proteins (1)

ProteinDefinitionTaxonomy
Cholesteryl ester transfer proteinA cholesteryl ester transfer protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:P11597]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
niacinNiacin: A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties.

nicotinic acid : A pyridinemonocarboxylic acid that is pyridine in which the hydrogen at position 3 is replaced by a carboxy group.

vitamin B3 : Any member of a group of vitamers that belong to the chemical structural class called pyridines that exhibit biological activity against vitamin B3 deficiency. Vitamin B3 deficiency causes a condition known as pellagra whose symptoms include depression, dermatitis and diarrhea. The vitamers include nicotinic acid and nicotinamide (and their ionized and salt forms).
pyridine alkaloid;
pyridinemonocarboxylic acid;
vitamin B3
antidote;
antilipemic drug;
EC 3.5.1.19 (nicotinamidase) inhibitor;
Escherichia coli metabolite;
human urinary metabolite;
metabolite;
mouse metabolite;
plant metabolite;
vasodilator agent
ursolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
geroprotector;
plant metabolite
torcetrapib(trifluoromethyl)benzenes;
carbamate ester;
quinolines
anticholesteremic drug;
CETP inhibitor
sb 203580imidazoles;
monofluorobenzenes;
pyridines;
sulfoxide
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent
delta-8-tetrahydrocannabinol1-benzopyran
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source

alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group.
1,4-benzoquinones;
ansamycin;
carbamate ester;
secondary amino compound;
tertiary amino compound
Hsp90 inhibitor
tanespimycinCP 127374: analog of herbimycin A1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound
antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
dalcetrapibdalcetrapib: inhibits cholesteryl ester transfer protein (CETP)anilide
am-411
sc 795
3-((3-(4-chloro-3-ethylphenoxy)phenyl)(3-(1,1,2,2-tetrafluoroethoxy)benzyl)amino)-1,1,1-trifluoropropan-2-ol3-((3-(4-chloro-3-ethylphenoxy)phenyl)(3-(1,1,2,2-tetrafluoroethoxy)benzyl)amino)-1,1,1-trifluoropropan-2-ol: inhibits cholesteryl ester transfer protein; structure in first source
amg 3AMG 3: structure in first source
km-233KM-233: used for the treatment of high-grade glioma; structure in first source
mk 0354
anacetrapib
gdc 0941pictrelisib : A sulfonamide composed of indazole, morpholine, and methylsulfonyl-substituted piperazine rings bound to a thienopyrimidine ring.indazoles;
morpholines;
piperazines;
sulfonamide;
thienopyrimidine
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
skepinone-lskepinone-L: a dibenzosuberone-type p38 MAPK inhibitor; structure in first source
evacetrapibbenzazepine