Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of the directed movement of cholesterol within cells. [GOC:mah]
Intracellular cholesterol transport is a complex and tightly regulated process that ensures the proper balance of cholesterol levels within cells. This process involves the coordinated action of various proteins and pathways to maintain cholesterol homeostasis, which is essential for cell signaling, membrane structure, and hormone production.
Cholesterol is a lipid molecule that is synthesized in the liver and taken up from the diet. Once inside the cell, cholesterol is transported to different compartments by specific carrier proteins. The key players in this process include:
1. **Acyl-CoA:cholesterol acyltransferase (ACAT):** This enzyme esterifies cholesterol with fatty acids, forming cholesterol esters that are less soluble and more easily stored in lipid droplets.
2. **Sterol regulatory element-binding proteins (SREBPs):** These transcription factors regulate the expression of genes involved in cholesterol synthesis, uptake, and transport. SREBPs are synthesized as inactive precursors bound to the endoplasmic reticulum (ER) membrane. When cholesterol levels are low, SREBPs are proteolytically cleaved, releasing the active transcription factor that translocates to the nucleus and activates target genes.
3. **Low-density lipoprotein (LDL) receptor:** This receptor binds to LDL particles, which are the primary carriers of cholesterol in the blood. Upon binding, LDL is internalized by endocytosis and delivered to lysosomes for degradation, releasing cholesterol into the cell.
4. **High-density lipoprotein (HDL):** This lipoprotein acts as a scavenger for cholesterol in the periphery and transports it back to the liver for excretion.
**The regulation of intracellular cholesterol transport involves multiple levels of control:**
* **Feedback regulation:** The availability of cholesterol itself regulates its own synthesis and uptake. When cellular cholesterol levels are high, cholesterol directly inhibits the activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. High levels of cholesterol also inhibit the transcription of SREBPs, reducing the synthesis of LDL receptors and enzymes involved in cholesterol synthesis.
* **Hormonal regulation:** Hormones like insulin and glucagon also play a role in cholesterol metabolism. Insulin stimulates cholesterol synthesis, while glucagon inhibits it.
* **Cellular signaling:** The balance of cholesterol levels is also influenced by various signaling pathways, such as those mediated by protein kinase A, protein kinase C, and MAP kinases. These pathways can modulate the expression and activity of key proteins involved in cholesterol transport.
* **Lipid droplet dynamics:** The storage and release of cholesterol from lipid droplets are tightly controlled. The process of cholesterol esterification by ACAT and the subsequent mobilization of cholesterol esters from lipid droplets are regulated by various signaling pathways and environmental cues.
In summary, the regulation of intracellular cholesterol transport is a complex and dynamic process involving multiple levels of control. This intricate system ensures that cholesterol levels are maintained within a tight range, which is crucial for the proper functioning of cells and tissues. Dysregulation of cholesterol transport can contribute to the development of various diseases, including atherosclerosis and cancer.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Sigma intracellular receptor 2 | A sigma intracellular receptor 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q5BJF2] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| astemizole | astemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position. Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects. | benzimidazoles; piperidines | anti-allergic agent; anticoronaviral agent; H1-receptor antagonist |
| carbetapentane | carbetapentane: RN given refers to parent cpd | benzenes | |
| chloroquine | chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis. Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. | aminoquinoline; organochlorine compound; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; autophagy inhibitor; dermatologic drug |
| haloperidol | haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| hydroxychloroquine | hydroxychloroquine : An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions. Hydroxychloroquine: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) | aminoquinoline; organochlorine compound; primary alcohol; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; dermatologic drug |
| moclobemide | moclobemide : A member of the class of benzamides that is benzamide substituted by a chloro group at position 4 and a 2-(morpholin-4-yl)ethyl group at the nitrogen atom. It acts as a reversible monoamine oxidase inhibitor and is used in the treatment of depression. Moclobemide: A reversible inhibitor of monoamine oxidase type A; (RIMA); (see MONOAMINE OXIDASE INHIBITORS) that has antidepressive properties. | benzamides; monochlorobenzenes; morpholines | antidepressant; environmental contaminant; xenobiotic |
| nemonapride | N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide : A benzamide obtained by formal condensation of the carboxy group of 5-chloro-2-methoxy-4-(methylamino)benzoic acid with the amino group of 1-benzyl-2-methylpyrrolidin-3-amine. | benzamides; monochlorobenzenes; monomethoxybenzene; N-alkylpyrrolidine; secondary amino compound; secondary carboxamide; substituted aniline | |
| 1,3-ditolylguanidine | 1,3-ditolylguanidine: structure given in first source; a selective ligand for the sigma binding sites in the brain | toluenes | |
| 4-toluic acid | 4-toluic acid: RN given refers to parent cpd; structure p-toluic acid : A methylbenzoic acid in which the methyl substituent is located at position 4. | methylbenzoic acid | |
| methyl-4-tyramine | methyl-4-tyramine: found in barley malt; RN given refers to parent cpd; structure given in first source | tyramines | mouse metabolite |
| azaperone | azaperone : An N-arylpiperazine that is 2-(piperazin-1-yl)pyridine in which the amino hydrogen is replaced by a 3-(4-fluobenzoyl)propyl group. Used mainly as a tranquiliser for pigs and elephants. Azaperone: A butyrophenone used in the treatment of PSYCHOSES. | aminopyridine; aromatic ketone; monofluorobenzenes; N-alkylpiperazine; N-arylpiperazine; tertiary amino compound | antipsychotic agent; dopaminergic antagonist |
| clemastine | clemastine : 2-[(2R)-1-Methylpyrrolidin-2-yl]ethanol in which the hydrogen of the hydroxy group is substituted by a 1-(4-chlorophenyl)-1-phenylethyl group (R configuration). An antihistamine with antimuscarinic and moderate sedative properties, it is used as its fumarate salt for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions. Clemastine: A histamine H1 antagonist used as the hydrogen fumarate in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness. | monochlorobenzenes; N-alkylpyrrolidine | anti-allergic agent; antipruritic drug; H1-receptor antagonist; muscarinic antagonist |
| befol | |||
| adenosine-5'-carboxylic acid | purine nucleoside | ||
| pentazocine | Pentazocine: The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97) | benzazocine | |
| cannabidiol | cannabidiol : An cannabinoid that is cyclohexene which is substituted by a methyl group at position 1, a 2,6-dihydroxy-4-pentylphenyl group at position 3, and a prop-1-en-2-yl group at position 4. Cannabidiol: Compound isolated from Cannabis sativa extract. | olefinic compound; phytocannabinoid; resorcinols | antimicrobial agent; plant metabolite |
| pd 144418 | |||
| lu 28-179 | Lu 28-179: sigma(2) ligand and lysosomotropic agent; structure in first source | ||
| n-cyclopropyl adenosine-5'-carboxamide | |||
| PB28 | PB28 : A member of the class of tetralins that is tetralin that is substituted by 3-(4-cyclohexylpiperazin-1-yl)propyl and methoxy groups at positions 1 and 5, respectively. It is a sigma 2 (sigma2) receptor agonist (Ki = 0.68 nM) and exhibits antineoplastic and anti SARS-CoV-2 activities. | aromatic ether; piperazines; tetralins | anticoronaviral agent; antineoplastic agent; apoptosis inducer; sigma-2 receptor agonist |
| pf 04457845 | |||
| e-52862 | |||
| skepinone-l | skepinone-L: a dibenzosuberone-type p38 MAPK inhibitor; structure in first source | ||
| wms 1410 | |||
| dolutegravir | difluorobenzene; monocarboxylic acid amide; organic heterotricyclic compound; secondary carboxamide | HIV-1 integrase inhibitor | |
| a-1155463 | A-1155463: a Bcl-X(L) inhibitor; structure in first source | ||
| MLI-2 | MLI-2 : A member of the class of indazoles that is 1H-indazole that is substituted at position 3 by a 6-(cis-2,6-dimethylmorpholin-4-yl)pyrimidin-4-yl group and at position 5 by a (1-methylcyclopropoxy)group. It is an inhibitor of leucine-rich repeat kinase 2 (LRRK2). | aromatic ether; cyclopropanes; indazoles; morpholines; pyrimidines; tertiary amino compound | EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor |