HydrolaseArachidonic acidLTA4HProstaglandinsLTB4MediatorsLTA4Receptor antagonistsPathwayReceptorsD'urgenceTraitementInjuryActivityScienceInhibitorCysteinyl-leukotrienesEnzymeBiosynthesisAminopeptidase activitySynthasePotentInhibitionEpoxideGeneInflammationAntagonismAssayLipoxinsReceptorPrecursorSimilarityComplexSubstrateHumanStudyTherapy
Hydrolase12
- The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA4 which is quickly hydrolyzed by the LTA4H (leukotriene A4 hydrolase) enzyme to produce LTB4, or synthesized by LTC4S (leukotriene C4 synthase) with the addition of glutathione to produce LTC4 which can be further metabolized to produce LTD4 (leukotriene D4) and LTE4 (leukotriene E4). (wikipedia.org)
- Leukotriene A 4 hydrolase (LTA 4 H) is a bi-functional enzyme that promotes a pro-inflammatory epoxy hydrolase (EH) pathway and an anti-inflammatory aminopeptidase (AP) pathway. (gmu.edu)
- DESCRIPTION (provided by applicant): The objective of this proposal is to exploit a newly discovered anti-inflammatory function involving the aminopeptidase activity of the leukotriene A4 hydrolase for the treatment of pulmonary emphysema. (sbir.gov)
- The leukotrieneA4 hydrolase is a dual-functioning enzyme with dichotomously opposing functions. (sbir.gov)
- The C-terminal domain of leukotriene A4 hydrolase. (eu.org)
- Celtaxsys, Inc., a private biopharmaceutical company developing a new class of drugs to treat chronic inflammatory disorders, today announced the initiation of a first-in-human Phase 1 clinical study of CTX-4430, which blocks the pro-inflammatory enzyme Leukotriene A4 Hydrolase (LTA4H). (benzinga.com)
- CTX-4430 works by inhibiting Leukotriene A4 Hydrolase (LTA4H), the major rate-limiting step in Leukotriene B4 (LTB4) production. (benzinga.com)
- With the conserved Zn(2+)-binding motifs HEXXH and NEXFA as well as the N-terminal substrate-anchoring glutamate residues, F3 together with the leukotriene A4 hydrolase, represents a novel gluzincin subfamily of aminoproteases. (rcsb.org)
- DG051 is a first-in-class, small-molecule inhibitor of leukotriene A4 hydrolase (LTA4H) discovered by deCODE's chemistry unit and being developed for the prevention of heart attack. (decode.com)
- Phylogenetic analysis of Q and leukotriene A-4 hydrolase-like gene orthologs, which were colinear among the three species, showed that Brachypodium is more closely related to wheat than rice, which agrees with previous studies. (usda.gov)
- Genetic regulation of expression of leukotriene A4 hydrolase. (cdc.gov)
- Ubenimex is an oral, small-molecule inhibitor of leukotriene A4 hydrolase, which regulates the production of leukotriene B4 (LTB4), an inflammatory mediator implicated in PAH. (thelymphielife.com)
Arachidonic acid12
- Following the biosynthesis of eicosanoid, triggered as a result of infection or inflammation, the resulting arachidonic acid substrate is released from the cell membrane phospholipid will enter the lipooxygenase pathway to produce leukotriene A4. (wikipedia.org)
- The lipooxygenase pathway is one of several possible pathways including the cyclooxygenase pathway (also PGH synthase pathway), isoprostane pathway, and cytochrome P450 epoxygenases pathway following the arachidonic acid metabolism, but is the only pathway in which the subsequent steps will lead to the production of leukotrienes. (wikipedia.org)
- The arachidonic acid, released by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors. (hindawi.com)
- Cysteinyl leukotrienes (Cys-LTs) are potent inflammatory lipid mediators derived from the 5-lypoxygenase (5-LO) pathway of arachidonic acid (AA) metabolism [ 1 ], initially identified to have important effects on pathogenetic aspects of allergic rhinitis and bronchial asthma and approved in the late 1990s for the relief of perennial and seasonal allergic rhinitis symptoms, and the treatment of mild persistent bronchial asthma [ 2 - 5 ]. (hindawi.com)
- 5-Lipoxygenase, Human, Recombinant, S. fruigiperda 5-Lipoxygenase, Human, Recombinant, S. frugiperda E.C 1.13.11.34, catalyzes the formation of 5(S)-HpETE from arachidonic acid and its subsequent conversion to leukotriene A4. (sigmaaldrich.com)
- 5-LO catalyzes the formation of 5(S)-HpETE from arachidonic acid and its subsequent conversion to leukotriene A 4 . (sigmaaldrich.com)
- Leukotriene biosynthesis: direct chemical ionization mass spectrometry of underivatized arachidonic acid metabolites. (cdc.gov)
- The usefulness of direct chemical ionization (DCI) mass spectrometry for obtaining simultaneous information on both the molecular ion and diagnostic fragment ions of underivatized arachidonic-acid, 5- hydroperoxyeicosatetraenoic-acid, 15-hydroperoxyeicosatetraenoic- acid, leukotriene-B4 (LTB4), and of leukotriene-A4 (LTA4) free acid was described. (cdc.gov)
- In organic chemistry, Leukotrienes are a subclass of organic compounds in the eicosanoids subclass of the fatty acyl class [FA class] within the lipids superclass , consisting of eicosanoids containing a hydroxyl group attached to the aliphatic chain of an arachidonic acid. (wellnessadvantage.com)
- Leukotrienes may be derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. (wellnessadvantage.com)
- Description: The ALOX5 gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. (glideruniversity.org)
- The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). (glideruniversity.org)
LTA4H1
- LTA4H is encoded by one of the genes in the leukotriene pathway deCODE has linked to increased risk of heart attack. (decode.com)
Prostaglandins4
- Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. (ed.ac.uk)
- The term "eicosanoids" includes prostaglandins (PGs), tromboxanes (TX), leukotrienes (LTs), and hydroxyl-eicosatetraenoic acid made by polyunsaturated 20-carbon fatty acids (PUFA), including the most abundant and biological precursor AA [ 21 ]. (hindawi.com)
- Eicosanoids include prostaglandins (the most important), prostacyclins, leukotrienes, and thromboxanes, which are responsible for many of the beneficial effects of the good fats. (wellnessadvantage.com)
- Among the eicosanoid receptors are receptors for the prostaglandins , thromboxanes, and leukotrienes. (wellnessadvantage.com)
LTB44
- Leukotriene A4 (LTA4) is a leukotriene, and is the precursor for the productions of LTB4 (leukotriene B4) and LTC4 (leukotriene C4). (wikipedia.org)
- Dose-dependent reduction of leukotriene B4 (LTB4): DG051 was shown to reduce LTB4 production in a dose-dependent manner, with a peak reduction of more than 70% versus baseline after 7 days of treatment. (decode.com)
- The at-risk versions of these genes confer increased risk of heart attack by increasing the production of the pro-inflammatory molecule leukotriene B4 (LTB4). (decode.com)
- The Ultra study is designed to assess the effectiveness of Ubenimex blocking the production of Leukotriene B4 (LTB4) … Leukotriene B4 (LTB4) is a naturally-occurring inflammatory substance known to be elevated in both preclinical models of secondary lymphedema as well as human lymphedema disease. (thelymphielife.com)
Mediators2
- Leukotrienes are important mediators of a number of inflammatory and allergic conditions. (glideruniversity.org)
- Biosynthesis of lipid mediators including the leukotrienes, lipoxins, eoxins, resolvins, and protectins entails the lipoxygenase (LOX) catalyzed synthesis of an allylic epoxide intermediate, designated as leukotriene A4 (LTA4) and LTA analogues, and heretofore considered too unstable for direct structural characterization. (vanderbilt.edu)
LTA41
- As proof of concept, human 15-LOX-1 was shown to convert 15S-hydroperoxyeicosatetraenoic acid (15S-HPETE) to the LTA analogue, 14,15-LTA4 (thus identifying eoxin A4). (vanderbilt.edu)
Receptor antagonists1
- For these, reasons both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested for inducing beneficial effects at different stages of the atherosclerosis process and may represent a new therapeutic target in the treatment of atherosclerotic vessel diseases, in particular in acute coronary syndrome. (hindawi.com)
Pathway1
- For these reasons, the leukotriene pathway may represent an alternative therapeutic target in the treatment of atherosclerotic vessel diseases [ 6 , 13 , 14 ]. (hindawi.com)
Receptors1
- 46. Biochemistry and biology of leukotriene B4 receptors. (ncgmlipidsp.jp)
D'urgence2
- 0,05) , les participantes ayant eu nettement moins recours à des doses d'urgence d''ibuprofène lorsqu'elles prenaient de l'huile de poisson. (who.int)
- Cette étude visait à évaluer l'épidémiologie de l'asthme et les facteurs de risque d'hospitalisation chez des enfants consultant en ambulatoire dans un service de soins d'urgence d'un centre hospitalier universitaire à Sohag (Égypte). (who.int)
Traitement1
- À l'analyse de régression multivariée, les facteurs de risque d'hospitalisation importants étaient les suivants : une toux associée à une dyspnée comme symptômes initiaux, un traitement prophylactique en cours et la présence du symptômes continus (de jour comme de nuit). (who.int)
Injury1
- Many studies regarding myocardial ischemia and reperfusion show that leukotriene signaling may be involved in the development of ischemic injury. (hindawi.com)
Activity1
- LTA 4 H EH activity catalyzes the hydrolysis of leukotriene A 4 (LTA 4 ) to the neutrophil chemoattractant leukotriene B 4 (LTB 4 ), while AP activity hydrolyzes the tripeptide proline-glycine-proline (PGP) to clear neutrophils in the lungs. (gmu.edu)
Science1
- In lipid science, Leukotrienes [FA0302] are a family of biologically active organic compounds in the lipid science , Eicosanoids subclass in the fatty acyl class [FA class] of the lipids superclass . (wellnessadvantage.com)
Inhibitor6
- Seminiferous tubular dilatation with its sequel of atrophy has been reported for a number of chemicals, including the fungicide carbendazim, a PDE4 inhibitor, a leukotriene inhibitor, and endothelin antagonists. (nih.gov)
- 2011. Efferent duct toxicity with secondary testicular changes in rats following administration of a novel leukotriene A4 hydrolase inhibitor. (nih.gov)
- The cell-free media from MWCNT-polarized macrophages induced the migration of neutrophilic cells (differentiated from HL-60), which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, an LTB4 receptor antagonist, but not NS-398, a cyclooxygenase 2 inhibitor, revealing LTB4 as a major mediator of neutrophil chemotaxis from MWCNT-polarized macrophages. (cdc.gov)
- Zileuton is an antiinflammatory leukotriene pathway inhibitor classified as an inhibitor of the enzyme 5-lipoxygenase that is used in the treatment of asthma and allergic rhinitis. (nih.gov)
- Zileuton (zye loo' ton) is an inhibitor of the enzyme 5-lipoxygenase which is responsible for the conversion of arachidonic acid into leukotriene A4, a potent mediator of the inflammatory cascade that plays a central role in asthma and allergic rhinitis. (nih.gov)
- Ubenimex is an oral, small-molecule inhibitor of leukotriene A4 hydrolase, which regulates the production of leukotriene B4 (LTB4), an inflammatory mediator implicated in PAH. (thelymphielife.com)
Cysteinyl-leukotrienes4
- LEUKOTRIENE B4 and cysteinyl-leukotrienes. (nih.gov)
- Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease. (uchicago.edu)
- MEASUREMENTS AND MAIN RESULTS: Here, in samples from 26 acute respiratory distress syndrome patients, we examined plasma levels of select specialized proresolving mediators that promote lung injury resolution in preclinical systems, namely lipoxin A4 and maresin 1, and select prophlogistic lipid mediators linked to acute respiratory distress syndrome pathogenesis, namely cysteinyl leukotrienes and thromboxane B2. (nih.gov)
- These mediators were detected by sensitive enzyme-linked immunosorbent assay: lipoxin A4 (assay range) (8.2-5,000 pg/mL), maresin 1 (7.8-1,000 pg/mL), cysteinyl leukotrienes (7.8-1,000 pg/mL), and thromboxane B2 (15.6-2,000 pg/mL). (nih.gov)
Enzyme2
- The leukotrieneA4 hydrolase is a dual-functioning enzyme with dichotomously opposing functions. (sbir.gov)
- Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. (nih.gov)
Biosynthesis5
- Following the biosynthesis of eicosanoid, triggered as a result of infection or inflammation, the resulting arachidonic acid substrate is released from the cell membrane phospholipid will enter the lipooxygenase pathway to produce leukotriene A4. (wikipedia.org)
- The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. (nih.gov)
- Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis. (cdc.gov)
- Association between genetic variants of the leukotriene biosynthesis pathway and the risk of stroke: a case-control study in the Chinese Han population. (cdc.gov)
- While omega-3 fatty acids are utilized for the biosynthesis of prostaglandin E3, the omega-6 fatty acid, GLA, is an important precursor of prostaglandin E1. (dralexrinehart.com)
Aminopeptidase activity1
- DESCRIPTION (provided by applicant): The objective of this proposal is to exploit a newly discovered anti-inflammatory function involving the aminopeptidase activity of the leukotriene A4 hydrolase for the treatment of pulmonary emphysema. (sbir.gov)
Synthase1
- Azelastine has mast cell-stabilizing properties that prevent the release of interleukin-6, tryptase, histamine, and TNF-alpha 2 from mast cells, and has been shown to reduce mediators of mast cell degranulation such as leukotrienes in the nasal lavage of patients with rhinitis, 1 as well as inhibiting their production and release from eosinophils (potentially via inhibition of phospholipase A 2 and leukotriene C 4 synthase). (drugbank.com)
Potent1
- 3. Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors. (nih.gov)
Inhibition1
- 4. Dual anti-inflammatory and selective inhibition mechanism of leukotriene A4 hydrolase/aminopeptidase: insights from comparative molecular dynamics and binding free energy analyses. (nih.gov)
Epoxide2
- Hydrolyzes an epoxide moiety of leukotriene A4 (LTA-4) to form leukotriene B4 (LTB-4). (origene.com)
- Alternatively, leukotriene A4 is converted into LEUKOTRIENE C4 by glutathione-S-transferase or into 5,6-di-HETE by the epoxide-hydrolase. (nih.gov)
Gene2
Inflammation3
- Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis. (cdc.gov)
- Leukotriene B4-mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes. (uchicago.edu)
- These findings demonstrate that the NLRP3 inflammasome plays Leukotriene-A4 hydrolase an important role in DNA damage responses (DDR) to oxidative and genotoxic stress, supporting cell death, and ultimately cell death associated inflammation. (aktsignal.com)
Antagonism1
- Blockade of avidity and focal clustering of beta 2-integrin by cysteinyl leukotriene antagonism attenuates eosinophil adhesion. (uchicago.edu)
Assay1
- 7. A sensitive fluorigenic substrate for selective in vitro and in vivo assay of leukotriene A4 hydrolase activity. (nih.gov)
Lipoxins1
- This book also considers lipoxins and third-generation peptidoleukotriene receptor antagonists, and then concludes with a summary of the physiological and pathophysiological effects of leukotrienes and lipoxins in a variety of organs. (elsevier.com)
Receptor2
- Leukotriene B4 receptor-1 mediates intermittent hypoxia-induced atherogenesis. (uchicago.edu)
- cysteinyl leukotriene receptor 1 [Sour. (gsea-msigdb.org)
Precursor1
- Epóxido alílico inestable formado a partir del precursor inmediato 5-HPETE por la retirada estéreo específica de un protón en C-10 y deshidratación. (bvsalud.org)
Similarity2
- Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). (nih.gov)
- Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4) (By similarity). (gliome.org)
Complex1
- The biologically active components of the complex are nystatin A1, A2, and A3. (lookformedical.com)
Substrate1
- Cholesterol EH and leukotriene A4 hydrolase are two EHs with very limited substrate specificity. (nih.gov)
Human1
- 19. Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin. (nih.gov)
Study1
- Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial. (ox.ac.uk)
Therapy1
- 11. Leukotriene A4 hydrolase as a target for cancer prevention and therapy. (nih.gov)