Page last updated: 2024-10-24

low-density lipoprotein particle clearance

Definition

Target type: biologicalprocess

The process in which a low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded. [GOC:BHF, GOC:mah]

Low-density lipoprotein (LDL) particle clearance is a critical process in lipid metabolism, ensuring the removal of cholesterol from the bloodstream and preventing its accumulation in the arteries. The process involves several steps and key players:

1. **LDL Binding to Receptors:** LDL particles bind to LDL receptors (LDLRs) on the surface of liver cells (hepatocytes), as well as other cell types. This binding is mediated by the apolipoprotein B-100 (apoB-100) molecule on the LDL particle.

2. **Endocytosis:** Upon binding, the LDLR-LDL complex is internalized into the cell through a process called endocytosis. The plasma membrane invaginates, forming a vesicle that encloses the complex.

3. **Lysosomal Degradation:** The vesicle fuses with lysosomes, organelles containing enzymes that degrade the LDL particle. The LDL particle is broken down into its constituent components, including cholesterol.

4. **Cholesterol Metabolism:** The liberated cholesterol is either used by the cell for various processes or esterified and stored in the form of cholesteryl esters.

5. **LDLR Recycling:** The LDLRs are recycled back to the cell surface after the LDL particle is degraded. This process ensures efficient LDL clearance.

6. **Other Pathways:** Besides receptor-mediated endocytosis, LDL can be taken up by scavenger receptors on macrophages, but this is less efficient and can contribute to the formation of foam cells in atherosclerosis.

7. **Regulation:** The expression of LDLRs is tightly regulated, influenced by factors like cholesterol levels, hormones (e.g., insulin, thyroid hormone), and statins (drugs that lower cholesterol levels).

8. **Consequences of Dysregulation:** Impaired LDL clearance due to genetic defects in LDLRs, high LDL levels, or other factors can lead to hypercholesterolemia and increased risk of atherosclerosis and cardiovascular disease.'
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Proteins (11)

ProteinDefinitionTaxonomy
Neutral cholesterol ester hydrolase 1A neutral cholesterol ester hydrolase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6PIU2]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)
Sterol O-acyltransferase 2A sterol O-acyltransferase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75908]Homo sapiens (human)
Diacylglycerol O-acyltransferase 2A diacylglycerol O-acyltransferase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96PD7]Homo sapiens (human)
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)
Neutral cholesterol ester hydrolase 1A neutral cholesterol ester hydrolase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6PIU2]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)
Low-density lipoprotein receptorA low-density lipoprotein receptor that is encoded in the genome of human. [PRO:DNx, UniProtKB:P01130]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 (40)

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
1,6-bis(cyclohexyloximinocarbonyl)hexane1,6-bis(cyclohexyloximinocarbonyl)hexane: selective inhibitor of canine platelet diglyceride lipasecarbamate ester;
organonitrogen compound
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
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
s 1033(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide
anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
orlistatorlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.

Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative
anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
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
ol-135
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
pf-04620110PF-04620110: a DGAT1 inhibitor; structure in first source
pf-06424439PF-06424439: an inhibitor of diacylglycerol acyltransferase 2; structure in first source