Gene Association: LTB4R2
UniProt Search:
LTB4R2 (PROTEIN_CODING)
Function Description: leukotriene B4 receptor 2
found 37 associated metabolites with current gene based on the text mining result from the pubmed database.
Purpurin
CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4870; ORIGINAL_PRECURSOR_SCAN_NO 4868 CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4852; ORIGINAL_PRECURSOR_SCAN_NO 4850 CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4850; ORIGINAL_PRECURSOR_SCAN_NO 4849 CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4850; ORIGINAL_PRECURSOR_SCAN_NO 4848 CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4861; ORIGINAL_PRECURSOR_SCAN_NO 4860 CONFIDENCE standard compound; INTERNAL_ID 760; DATASET 20200303_ENTACT_RP_MIX507; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4843; ORIGINAL_PRECURSOR_SCAN_NO 4841 CONFIDENCE Reference Standard (Level 1); INTERNAL_ID 8372 D004396 - Coloring Agents Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1]. Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1].
11,12-Epoxyeicosatrienoic acid
11,12-Epoxyeicosatrienoic acid (CAS: 81276-02-0) is an epoxyeicosatrienoic acid (EET). Induction of CYP2C8 in native coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as endothelium-derived hyperpolarizing factor-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP2C8 antisense oligonucleotides resulted in decreased levels of CYP2C and attenuated the endothelium-derived hyperpolarizing factor-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of the endothelium-derived hyperpolarizing factor-mediated relaxation in the porcine coronary artery, and CYP2C8 fulfills the criteria for the coronary endothelium-derived hyperpolarization factor synthase. The role of EETs in the regulation of the cerebral circulation has become more important since it was realized that EETs are produced in another specialized cell type of the brain, the astrocytes. It has become evident that EETs released from astrocytes may mediate cerebral functional hyperemia. Molecular and pharmacological evidence has shown that neurotransmitter release and spillover onto astrocytes can generate EETs. Since these EETs may reach the vasculature via astrocyte foot-processes, they have the same potential as their endothelial counterparts to hyperpolarize and dilate cerebral vessels. P450 enzymes contain heme in their catalytic domain and nitric oxide (NO) appears to bind to these heme moieties and block formation of P450 products, including EETs. Thus, there appears to be crosstalk between P450 enzymes and NO/NO synthase. The role of fatty acid metabolites and cerebral blood flow becomes even more complex in light of data demonstrating that cyclooxygenase products can act as substrates for P450 enzymes (PMID: 17494091, 17434916, 17406062, 17361113, 15581597, 11413051, 10519554). EETs function as autocrine and paracrine mediators. During inflammation, a large amount of arachidonic acid (AA) is released into the cellular milieu and cyclooxygenase enzymes convert this AA to prostaglandins that in turn sensitize pain pathways. However, AA is also converted into natural EETs by cytochrome P450 enzymes. Cytochrome P450 (CYP) epoxygenases convert arachidonic acid into four epoxyeicosatrienoic acid (EET) regioisomers, 5,6-, 8,9-, 11,12-, and 14,15-EET. EETs produce vascular relaxation by activating smooth muscle large-conductance Ca2+-activated K+ channels. In particular, 11,12-epoxy-5Z,8Z,14Z-eicosatrienoic acid has been shown to play a role in the recovery of depleted Ca2+ pools in cultured smooth muscle cells (PMID: 9368016). In addition, EETs have anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and the brain. EET levels are typically regulated by soluble epoxide hydrolase (sEH), the major enzyme degrading EETs. Specifically, soluble epoxide hydrolase (sEH) converts EETs into dihydroxyeicosatrienoic acids. 11,12-EpETrE or 11,12-epoxy-5Z,8Z,14Z-eicosatrienoic acid is an epoxyeicosatrienoic acid or an EET derived from arachadonic acid. EETs function as autacrine and paracrine mediators. During inflammation, a large amount of arachidonic acid (AA) is released into the cellular milieu and cyclooxygenase enzymes convert this AA to prostaglandins that in turn sensitize pain pathways. However, AA is also converted to natural epoxyeicosatrienoic acids (EETs) by cytochrome P450 enzymes. Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four epoxyeicosatrienoic acid (EET) regioisomers, 5,6-, 8,9-, 11,12-, and 14,15-EET. EETs produce vascular relaxation by activating smooth muscle large-conductance Ca2+-activated K+ channels. In particular, 11,12-epoxy-5Z,8Z,14Z-eicosatrienoic acid has been show to play a role in the recovery of depleted Ca2+ pools in cultured smooth muscle cells (PMID: 9368016). In addition, EETs have antiinflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. EET levels are typically regulated by soluble epoxide hydrolase (sEH), the major enzyme degrading EETs. Specifically, soluble epoxide hydrolase (sEH) converts EETs to dihydroxyeicosatrienoic acids. [HMDB] D002317 - Cardiovascular Agents > D014665 - Vasodilator Agents
Montelukast
Montelukast is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally. Montelukast blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene, and results in less inflammation. Because of its method of operation, it is not useful for the treatment of acute asthma attacks. Again because of its very specific locus of operation, it does not interact with other allergy medications such as theophylline. Montelukast is marketed in United States and many other countries by Merck & Co. with the brand name Singulair. It is available as oral tablets, chewable tablets, and oral granules. In India and other countries, it is also marketed under the brand name Montair®, produced by Indian company Cipla. R - Respiratory system > R03 - Drugs for obstructive airway diseases > R03D - Other systemic drugs for obstructive airway diseases > R03DC - Leukotriene receptor antagonists D019141 - Respiratory System Agents > D018927 - Anti-Asthmatic Agents > D020024 - Leukotriene Antagonists D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006727 - Hormone Antagonists D065693 - Cytochrome P-450 Enzyme Inducers > D065694 - Cytochrome P-450 CYP1A2 Inducers COVID info from clinicaltrial, clinicaltrials, clinical trial, clinical trials C78273 - Agent Affecting Respiratory System > C29712 - Anti-asthmatic Agent Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
12(S)-HPETE
12-HPETE is one of the six monohydroperoxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid (Leukotrienes). Reduction of the hydroperoxide yields the more stable hydroxyl fatty acid (+/-)12-HETE. A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. 12-HPETE is one of the six monohydroperoxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid (Leukotrienes). Reduction of the hydroperoxide yields the more stable hydroxyl fatty acid (+/-)12-HETE. D006401 - Hematologic Agents > D010975 - Platelet Aggregation Inhibitors D002317 - Cardiovascular Agents > D014662 - Vasoconstrictor Agents
Zafirlukast
Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily. Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages. R - Respiratory system > R03 - Drugs for obstructive airway diseases > R03D - Other systemic drugs for obstructive airway diseases > R03DC - Leukotriene receptor antagonists D019141 - Respiratory System Agents > D018927 - Anti-Asthmatic Agents > D020024 - Leukotriene Antagonists D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006727 - Hormone Antagonists C78273 - Agent Affecting Respiratory System > C29712 - Anti-asthmatic Agent
12-HETE
12-Hydroxyeicosatetraenoic acid (CAS: 71030-37-0), also known as 12-HETE, is an eicosanoid, a 5-lipoxygenase metabolite of arachidonic acid. 5-Lipoxygenase (LO)-derived leukotrienes are involved in inflammatory glomerular injury. LO product 12-HETE is associated with the pathogenesis of hypertension and may mediate angiotensin II and TGFbeta induced mesangial cell abnormality in diabetic nephropathy. 12-HETE is markedly elevated in the psoriatic lesions. 12-HETE is a vasoconstrictor eicosanoid that contributes to high blood pressure in (renovascular) hypertension and pregnancy-induced hypertension. A significant percentage of patients suffering from a selective increase in plasma LDL cholesterol (type IIa hyperlipoproteinemia) exhibits increased platelet reactivity. This includes enhanced platelet responsiveness against a variety of platelet-stimulating agents ex vivo and enhanced arachidonic acid metabolism associated with increased generation of arachidonic acid metabolites such as 12-HETE, and secretion of platelet-storage products (PMID: 7562532, 12480795, 17361113, 8498970, 1333255, 2119633). 12-HETE is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumour cell metastatic potential through activation of protein kinase C. 12-HETE has a diversity of biological actions and is generated by a number of tissues including the renal glomerulus and the vasculature. 12-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. 12-HETE is a neuromodulator that is synthesized during ischemia. Its neuronal effects include attenuation of calcium influx and glutamate release as well as inhibition of AMPA receptor (AMPA-R) activation. 12-HETE is found to be associated with peroxisomal biogenesis defect and Zellweger syndrome, which are inborn errors of metabolism.
15-HETE
15-HETE is a hydroxyeicosatetraenoic acid. Hydroxyeicosatetraenoic acids (HETEs) are formed by the 5-, 12-, and 15-lipoxygenase (LO) pathways. The 5- and 12-LO products are mainly proinflammatory in the skin whereas the main 15-LO product 15-HETE has antiinflammatory capacities. In vitro, 15-HETE has been shown to inhibit LTB4 formation, 12-HETE formation, and specifically inhibits the neutrophil chemotactic effect of LTB4. The inhibition of LTB4 formation is probably due to modulation of the 5-LO because no changes in PGE2 formation have been determined. In vivo, 15-HETE inhibits LTB4-induced erythema and edema, and reduces LTB4 in the synovial fluid of carragheenan-induced experimental arthritis in dogs. 15-HETE also has some immunomodulatory effects. It inhibits the mixed lymphocyte reaction, induces generation of murine cytotoxic suppressor T cells, and it decreases interferon production by murine lymphoma cells. Furthermore, IL-4 and IL-13 have recently been shown to be potent activators of the 15-LO in mononuclear cells (PMID: 11104340). 15(S)-HETE is found to be associated with Zellweger syndrome, which is an inborn error of metabolism. 15(S)-HETE is a hydroxyeicosatetraenoic acid. Hydroxyeicosatetraenoic acids (HETEs) are formed by the 5-, 12- and 15-lipoxygenase (LO) pathways. 5- and 12-LO products are mainly proinflammatory in the skin whereas the main 15-LO product 15-HETE has antiinflammatory capacities. In vitro 15-HETE has been shown to inhibit LTB4 formation, 12-HETE formation and specifically inhibits the neutrophil chemotactic effect of LTB4. The inhibition of LTB4 formation is probably due to modulation of the 5-LO because no changes in PGE2 formation have been determined. In vivo, 15-HETE inhibits LTB4-induced erythema and edema, and reduces LTB4 in the synovial fluid of carragheenan-induced experimental arthritis in dogs. 15-HETE has also some immunomodulatory effects. It inhibits the mixed lymphocyte reaction, induces generation of murine cytotoxic suppressor T cells, and it decreases interferon production by murine lymphoma cells. Furthermore, IL-4 and IL-13 have recently been shown to be potent activators of the 15-LO in mononuclear cells. (PMID: 11104340) [HMDB] 15(S)-HETE. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=54845-95-3 (retrieved 2024-07-10) (CAS RN: 54845-95-3). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
5-KETE
5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE), 5-lipoxygenase product is a potent chemoattractant for neutrophils and eosinophils. Its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family.(PMID:18292294) [HMDB] 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE), 5-lipoxygenase product is a potent chemoattractant for neutrophils and eosinophils. Its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family.(PMID:18292294).
Leukotriene B4
A leukotriene composed of (6Z,8E,10E,14Z)-icosatetraenoic acid having (5S)- and (12R)-hydroxy substituents. It is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Chemical was purchased from CAY20110 (Lot 0439924-0).; Diagnostic ions: 335.1, 317.2, 195.1, 129.0, 115.0, 111.5
Leukotriene D4
Leukotriene D4 (LTD4) is a cysteinyl leukotriene. Cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. LTD4 is a pro-inflammatory mediator known to mediate its effects through specific cell-surface receptors belonging to the G-protein-coupled receptor family, namely the high-affinity CysLT1 (cysteinyl leukotriene 1) receptor. LTD4 is present at high levels in many inflammatory conditions, and areas of chronic inflammation have an increased risk for subsequent cancer development. LTD4 is associated with the pathogenesis of several inflammatory disorders, such as asthma and inflammatory bowel disease. Exposure to LTD4 increases survival and proliferation in intestinal epithelial cells. CysLT1 regulator is up-regulated in colon cancer tissue and LTD4 signalling facilitates the survival of cancer cells. LTD4 could reduce apoptosis in non-transformed epithelial cells. LTD4 causes up-regulation of beta-catenin through the CysLT1 receptor, PI3K (phosphoinositide 3-kinase), and GSK-3β (glycogen synthase kinase 3β). LTD4 induces beta-catenin translocation to the nucleus and activation of TCF/LEF family of transcription factors. LTD4 causes accumulation of free beta-catenin in non-transformed intestinal epithelial cells through the CysLT1 receptor, and this accumulation is dependent upon the activation of PI3K as well as GSK-3β inactivation (PMID: 16042577, 12607939). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and are able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signaling pathways. Leukotriene D4 (LTD4) is a cysteinyl leukotriene a family of potent inflammatory mediators. LTD4 is a pro-inflammatory mediator known to mediate its effects through specific cell-surface receptors belonging to the G-protein-coupled receptor family, namely the high-affinity CysLT1 (cysteinyl leukotriene 1) receptor. LTD4 is present at high levels in many inflammatory conditions, and areas of chronic inflammation have an increased risk for subsequent cancer development; LTD4 is associated with the pathogenesis of several inflammatory disorders, such as asthma and inflammatory bowel disease. Exposure to LTD4 increases survival and proliferation in intestinal epithelial cells. CysLT1 regulator is up-regulated in colon cancer tissue and LTD4 signalling facilitates the survival of cancer cells. LTD4 could reduce apoptosis in non-transformed epithelial cells. LTD4 causes up-regulation of b-catenin through the CysLT1 receptor, PI3K (phosphoinositide 3-kinase) and GSK-3b (glycogen synthase kinase 3b). LTD4 induces b-catenin translocation to the nucleus and activation of TCF/LEF family of transcription factors. LTD4 causes accumulation of free b-catenin in non-transformed intestinal epithelial cells through the CysLT1 receptor, and this accumulation is dependent upon the activation of PI3K as well as GSK-3b inactivation. (PMID: 16042577, 12607939)
12-HHTrE
12(S)-HHTrE is an unusual product of the cyclooxygenase (COX) pathway and one of the primary arachidonic acid metabolites of the human platelet.1 It is biosynthesized by thromboxane (TX) synthesis from prostaglandin H2 (PGH2) concurrently with TXA2. The biological role of 12(S)-HHTrE is uncertain. It is avidly oxidized to 12-oxoHTrE by porcine 15-hydroxy PGDH. [HMDB] 12(S)-HHTrE is an unusual product of the cyclooxygenase (COX) pathway and one of the primary arachidonic acid metabolites of the human platelet.1 It is biosynthesized by thromboxane (TX) synthesis from prostaglandin H2 (PGH2) concurrently with TXA2. The biological role of 12(S)-HHTrE is uncertain. It is avidly oxidized to 12-oxoHTrE by porcine 15-hydroxy PGDH.
Prostaglandin H2
Prostaglandin H2 (PGH2) is the first intermediate in the biosynthesis of all prostaglandins. Prostaglandins are synthesized from arachidonic acid by the enzyme COX-1 and COX-2, which are also called PGH synthase 1 and 2. These enzymes generate a reactive intermediate PGH2 which has a reasonably long half-life (90-100 s) but is highly lipophilic. PGH2 is converted into the biologically active prostaglandins by prostaglandin isomerases, yielding PGE2, PGD2, and PGF2, or by thromboxane synthase to make TXA2 or by prostacyclin synthase to make PGI2. Most nonsteroidal anti-inflammatory drugs such as aspirin and indomethacin inhibit both PGH synthase 1 and 2. A key feature for eicosanoid transcellular biosynthesis is the export of PGH2 or LTA4 from the donor cell as well as the uptake of these reactive intermediates by the acceptor cell. Very little is known about either process despite the demonstrated importance of both events. In cells, PGH2 rearranges nonenzymatically to LGs even in the presence of enzymes that use PGH2 as a substrate. When platelets form thromboxane A2 (TXA2) from endogenous arachidonic acid (AA), PGH2 reaches concentrations very similar to those of TXA2 and high enough to produce strong platelet activation. Therefore, platelet activation by TXA2 appears to go along with an activation by PGH2. The agonism of PGH2 is limited by the formation of inhibitory prostaglandins, especially PGD2 at higher concentrations. That is why thromboxane synthase inhibitors in PRP and at a physiological HSA concentration do not augment platelet activation (PMID: 2798452, 15650407, 16968946). Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and are able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signalling pathways. Prostaglandin h2, also known as pgh2 or 9s,11r-epidioxy-15s-hydroxy-5z,13e-prostadienoate, is a member of the class of compounds known as prostaglandins and related compounds. Prostaglandins and related compounds are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid. Thus, prostaglandin h2 is considered to be an eicosanoid lipid molecule. Prostaglandin h2 is practically insoluble (in water) and a weakly acidic compound (based on its pKa). Prostaglandin h2 can be found in a number of food items such as gooseberry, evergreen huckleberry, quince, and capers, which makes prostaglandin h2 a potential biomarker for the consumption of these food products. Prostaglandin h2 can be found primarily in human platelet tissue. In humans, prostaglandin h2 is involved in several metabolic pathways, some of which include magnesium salicylate action pathway, ketorolac action pathway, trisalicylate-choline action pathway, and salicylate-sodium action pathway. Prostaglandin h2 is also involved in a couple of metabolic disorders, which include leukotriene C4 synthesis deficiency and tiaprofenic acid action pathway. Prostaglandin h2 is acted upon by: Prostacyclin synthase to create prostacyclin Thromboxane-A synthase to create thromboxane A2 and 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) (see 12-Hydroxyheptadecatrienoic acid) Prostaglandin D2 synthase to create prostaglandin D2 Prostaglandin E synthase to create prostaglandin E2 Prostaglandin h2 rearranges non-enzymatically to: A mixture of 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) and 12-(S)-hydroxy-5Z,8Z,10E-heptadecatrienoic acid (see 12-Hydroxyheptadecatrienoic acid) Use of Prostaglandin H2: regulating the constriction and dilation of blood vessels stimulating platelet aggregation Effects of Aspirin on Prostaglandin H2: Aspirin has been hypothesized to block the conversion of arachidonic acid to Prostaglandin . D009676 - Noxae > D016877 - Oxidants > D010545 - Peroxides
Leukotriene A4
Leukotriene A4 (LTA4) is the first metabolite in the series of reactions leading to the synthesis of all leukotrienes. 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to LTA4.The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA4. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. (PMID: 10591081, 2820055). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signalling pathways. Leukotriene A4 (LTA4) is the first metabolite in the series of reactions leading to the synthesis of all leukotrienes. 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to LTA4.The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA4. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. (PMID: 10591081, 2820055)
Docebenone
D004791 - Enzyme Inhibitors > D016859 - Lipoxygenase Inhibitors C471 - Enzyme Inhibitor > C1322 - Lipooxygenase Inhibitor Docebenone (AA 861) is a potent, selective and orally active 5-LO (5-lipoxygenase) inhibitor.
20-Carboxy-leukotriene B4
20-Carboxyleukotriene B4 is an omega-oxidized metabolite of leukotriene B4 (LTB4). Neutrophil microsomes are known to oxidize 20-hydroxy-LTB4 (20-OH-LTB4) to its 20-oxo and 20-carboxy derivatives in the presence of NADPH. This activity has been ascribed to LTB4 omega-hydroxylase (cytochrome P-450LTB omega). Leukotriene B4 release from polymorphonuclear granulocytes of severely burned patients was reduced as compared to healthy donor cells. This decrease is due to an enhanced conversion of LTB4 into the 20-hydroxy- and 20-carboxy-metabolites and further to a decreased LTB4-synthesis. LTB4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/ 15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. (PMID 17623009, 7633595, 2155225, 3039534)Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signalling pathways.
Leukotriene E4
Leukotriene E4 (LTE4) is a cysteinyl leukotriene. Cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. LTE4 activates contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. LTE4 is metabolized from leukotriene C4 in a reaction catalyzed by gamma-glutamyl transpeptidase and a particulate dipeptidase from kidney (PMID: 12607939, 12432945, 6311078). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and are able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signaling pathways. Leukotriene E4 (LTE4) is a cysteinyl leukotriene. Cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. LTE4, activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. LTE4 is metabolized from leukotriene C4 in a reaction catalyzed by gamma-glutamyl transpeptidase and a particulate dipeptidase from kidney. (PMID: 12607939, 12432945, 6311078)
1,2,4-Trihydroxyanthraquinone
Purpurin is a trihydroxyanthraquinone derived from anthracene by substitution with oxo groups at C-9 and C-10 and with hydroxy groups at C-1, C-2 and C-4. It has a role as a biological pigment, a histological dye and a plant metabolite. Purpurin is a natural product found in Rubia argyi, Cinchona calisaya, and other organisms with data available. See also: Rubia tinctorum root (part of). A trihydroxyanthraquinone derived from anthracene by substitution with oxo groups at C-9 and C-10 and with hydroxy groups at C-1, C-2 and C-4. D004396 - Coloring Agents Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1]. Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1].
Leukotriene B4
Leukotriene B4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region, and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by omega-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the omega-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted in human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before omega-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. The term leukotriene was coined to indicate the presence of three conjugated double bonds within the 20-carbon structure of arachidonic acid as well as the fact that these compounds were derived from leucocytes such as PMNNs or transformed mast cells. Interestingly, most of the cells known to express 5-LO are of myeloid origin, which includes neutrophils, eosinophils, mast cells, macrophages, basophils, and monocytes. Leukotriene biosynthesis begins with the specific oxidation of arachidonic acid by a free radical mechanism as a consequence of interaction with 5-LO. The first enzymatic step involves the abstraction of a hydrogen atom from C-7 of arachidonate followed by the addition of molecular oxygen to form 5-HpETE (5-hydroperoxyeicosatetraenoic acid). A second enzymatic step is also catalyzed by 5-LO and involves removal of a hydrogen atom from C-10, resulting in the formation of the conjugated triene epoxide LTA4. LTA4 must then be released by 5-LO and encounter either LTA4-H (LTA4 hydrolase) or LTC4-S [LTC4 (leukotriene C4) synthase]. LTA4-H can stereospecifically add water to C-12 while retaining a specific double-bond geometry, leading to LTB4 [leukotriene B4, 5(S),12(R)-dihydroxy-6,8,10,14-(Z,E,E,Z)-eicosatetraenoic acid]. If LTA4 encounters LTC4-S, then the reactive epoxide is opened at C-6 by the thiol anion of glutathione to form the product LTC4 [5(S)-hydroxy-6(R)-S-glutathyionyl-7,9,11,14- (E,E,Z,Z)-eicosatetraenoic acid], essentially a glutathionyl adduct of oxidized arachidonic acid. Both of these terminal leukotrienes are biologically active in that specific GPCRs recognize these chemical structures and receptor recognition initiates complex intracellular signalling cascades. In order for these molecules to serve as lipid mediators, however, they must be released from the biosynthetic cell into the extracellular milieu so that they can encounter the corresponding GPCRs. Surprising features of this cascade include the recognition of the assembly of critical enzymes at the perinuclear region of the cell and even localization of 5-LO within the nucleus of some cells. Under some situations, the budding phagosome has been found to assemble these proteins. Non-enzymatic proteins such as FLAP are now known as critical partners of this protein-machine assembly. An unexpected pathway of leukotriene biosynthesis involves the transfer of the chemically reactive intermediate, LTA4, from the biosynthetic cell followed by conversion into LTB4 or LTC4 by other cells that do not express ...
20-Hydroxy-leukotriene B4
20-hydroxy- Leukotriene B4 (20-OH-LTB4) is an omega-hydroxylated metabolite of leukotriene B4 in human neutrophils. Elevated urinary concentrations of 20-OH-LTB4 and LTB4 are found in patients with Sjogren-Larsson syndrome (SLS, OMIM 270220), an autosomal recessively inherited neurocutaneous disorder caused by a deficiency of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH), which as an essential role in LTB4 metabolism. Preterm birth seems to be one of the features of the syndrome. The reason for the preterm birth is unclear. It is hypothesized that it relates to the defective LTB4 degradation in SLS. The pathological urinary excretion of LTB4 and 20-OH-LTB4 is a biochemical marker for SLS. Surprisingly, 20-OH-LTB4 concentrations are normal in CSF. Leukotriene B4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/ 15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. (PMID: 12709426, 9799565, 11408337, 17623009). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signalling pathways. 20-hydroxy- Leukotriene B4 (20-OH-LTB4) is an omega-hydroxylated metabolite of leukotriene B4 in human neutrophils. Elevated urinary concentrations of 20-OH-LTB4 and LTB4 are found in patients with Sjogren-Larsson syndrome (SLS, OMIM 270220), an autosomal recessively inherited neurocutaneous disorder caused by a deficiency of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH), which as an essential role in LTB4 metabolism. Preterm birth seems to be one of the features of the syndrome. The reason for the preterm birth is unclear. It is hypothesized that it relates to the defective LTB4 degradation in SLS. The pathological urinary excretion of LTB4 and 20-OH-LTB4 is a biochemical marker for SLS. Surprisingly, 20-OH-LTB4 concentrations are normal in CSF. Leukotriene B4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/ 15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. (PMID: 12709426, 9799565, 11408337, 17623009)
6-[2-Amino-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-5-hydroxyicosa-7,9,11,14-tetraenoic acid
zafirlukast
R - Respiratory system > R03 - Drugs for obstructive airway diseases > R03D - Other systemic drugs for obstructive airway diseases > R03DC - Leukotriene receptor antagonists D019141 - Respiratory System Agents > D018927 - Anti-Asthmatic Agents > D020024 - Leukotriene Antagonists D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006727 - Hormone Antagonists C78273 - Agent Affecting Respiratory System > C29712 - Anti-asthmatic Agent
Montelukast
R - Respiratory system > R03 - Drugs for obstructive airway diseases > R03D - Other systemic drugs for obstructive airway diseases > R03DC - Leukotriene receptor antagonists D019141 - Respiratory System Agents > D018927 - Anti-Asthmatic Agents > D020024 - Leukotriene Antagonists D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006727 - Hormone Antagonists D065693 - Cytochrome P-450 Enzyme Inducers > D065694 - Cytochrome P-450 CYP1A2 Inducers COVID info from clinicaltrial, clinicaltrials, clinical trial, clinical trials C78273 - Agent Affecting Respiratory System > C29712 - Anti-asthmatic Agent Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS CONFIDENCE standard compound; INTERNAL_ID 2745
Purpurin
D004396 - Coloring Agents Origin: Plant, Organic chemicals, Polycyclic compounds, Anthracenes Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1]. Purpurin is a natural anthraquinone compound from Rubia cordifolia L.. Purpurin has antidepressant-like effects[1].
12-Hete
A HETE that is icosa-5,8,10,14-tetraenoic acid substituted by a hydroxy group at position 12. It is a metabolite of arachidonic acid. A HETE having a (12S)-hydroxy group and (5Z)-, (8Z)-, (10E)- and (14Z)-double bonds.
Prostaglandin H2
D009676 - Noxae > D016877 - Oxidants > D010545 - Peroxides
Leukotriene E
A leukotriene that is (7E,9E,11Z,14Z)-icosa-7,9,11,14-tetraenoic acid substituted by a hydroxy group at position 5 (5S) and an L-cystein-S-yl group at position 6 (6R).
Leukotriene A4
A leukotriene that is the (5S,6S)-epoxy derivative of (7E,9E,11Z,14Z)-icosa-7,9,11,14-tetraenoic acid.
AA-861
D004791 - Enzyme Inhibitors > D016859 - Lipoxygenase Inhibitors C471 - Enzyme Inhibitor > C1322 - Lipooxygenase Inhibitor Docebenone (AA 861) is a potent, selective and orally active 5-LO (5-lipoxygenase) inhibitor.
12(S)-HPETE
D006401 - Hematologic Agents > D010975 - Platelet Aggregation Inhibitors D002317 - Cardiovascular Agents > D014662 - Vasoconstrictor Agents The (S)-enantiomer of 12-HPETE.
