Arachidonate 5-lipoxygenase

1534:-eicosatrienoic acid (5-HETrE), 5-oxo-6,8,11-eicosatrienoic acid (5-oxo-ETrE), LTA3, and LTC3; since LTA3 inhibits LTA hydrolase, mead acid metabolizing cells produce relatively little LTB3 and are blocked from metabolizing arachidonic acid to LTB4. On the other hand, 5-oxo-ETrE is almost as potent as 5-oxo-ETE as an eosinophil chemotactic factor and may thereby contribute to the development of physiological and pathological allergic responses. Presumably, the same metabolic pathways that follow ALOX5 in metabolizing arachidonic acid to the 4-series metabolites likewise act on mead acid to form these products. 1665:. This may be a reflection of the array of metabolites made by the Alox5 enzyme some of which possess opposing activities like the pro-inflammatory chemotactic factors and the anti-inflammatory specialized pro-resolving mediators. Alox5 and presumably human ALOX5 functions may vary widely depending on: the agents stimulating their activity; the types of metabolites that they form; the specific tissues responding to these metabolites; the times (e.g. early versus delayed) at which observations are made; and very likely various other factors. 1570:-eiosapentaenoic acid), to 5-hydroperoxy-eicosapentaenoic acid which is then converted to 5-series products that are structurally analogous to their arachidonic acid counterparts viz., 5-hydroxy-eicosapentaenoic acid (5-HEPE), 5-oxo-eiocosapentaenoic acid (5-oxo-HEPE), LTB5, LTC5, LTD5, and LTE5. Presumably, the same metabolic pathways that follow ALOX5 in metabolizing arachidonic acid to the 4-series metabolites likewise act on EPA to form these 5-series products. ALOX5 also cooperates with other lipoxygenase, 2134:. Zyleuton and zileuton CR cause elevations in liver enzymes in 2% of patients; the two drugs are therefore contraindicated in patients with active liver disease or persistent hepatic enzyme elevations greater than three times the upper limit of normal. Hepatic function should be assessed prior to initiating either of these drugs, monthly for the first 3 months, every 2–3 months for the remainder of the first year, and periodically thereafter; zileuton also has a rather unfavorable pharmacological profile (see 7440: 1299: 2272:

suppress inflammation depending on the relative roles these opposing metabolites have in regulating the particular type of reaction examined. Furthermore, the ALOX5-related tissue reactions studied to date are influenced by multiple genetic, environmental, and developmental variables that may influence the consequences of abnormalities in the expression or function of ALOX5. Consequently, abnormalities in the

784:. The physiological and/or pathological consequences of this slicing has yet to be defined. In one study, however, human brain tumors were shown to express three mRNA splice variants (2.7, 3.1, and 6.4 kb) in addition to the full 8.6 lb species; the abundance of the variants correlated with the malignancy of these tumors suggesting that they may play a role in the development of these tumors. 4670:

Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, Brockow K, Campo P, Celik G, Cernadas J, Cortellini G, Gomes E, Niżankowska-Mogilnicka E, Romano A, Szczeklik A, Testi S, Torres MJ, Wöhrl S, Makowska J (2013). "Classification and practical approach to the diagnosis and management

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or scaffold, thereby averting the enzyme's inactivation to promote its metabolic activity; depending on circumstance such as the presence of phospholipids and levels of ambient Ca, this binding also alters the relative levels of hydroperoxy versus epoxide (see arachidonic acid section below) products

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Zileuton is approved in the US for the prophylaxis and chronic treatment of allergic asthma; it is also used to treat chronic non-allergic reactions such as NSAID-induced non-allergic lung, nose, and conjunctiva reactions as well as exercise-induced asthma. Zileuton has shown some beneficial effects

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5-HEPE, 5-oxo-HEPE, LTB5, LTC5, LTD5, and LTE5 are generally less potent in stimulating cells and tissues than their arachidonic acid-derived counterparts; since their production is associated with reduced production of their arachidonic acid-derived counterparts, they may indirectly serve to reduce

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and may thereby contribute to eosinophil-based allergic reactions and diseases. These metabolites may also contribute to the progression of certain cancers such as those of the prostate, breast, lung, ovary, and pancreas. ALOX5 may be overexpressed in some of these cancers; 5-Oxo-ETE and to a lesser

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To date, however, neither LTB4 synthesis inhibitors (i.e. blockers of ALOX5 or LTA4 hydrolase) nor inhibitors of LTB4 receptors (BLT1 and BLT2) have turned out to be effective anti-inflammatory drugs. Furthermore, blockers of LTC4, LTD4, and LTE4 synthesis (i.e. ALOX5 inhibitors) as well as of LTC4

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ALOX5 contributes to the formation of PUFA metabolites that may promote (e.g. the leukotrienes, 5-oxo-ETE) but also to metabolites that inhibit (i.e. lipoxins, resolvins) diseases. Consequently, a given abnormality in the expression or activity of ALOX5 due to variations in its gene may promote or

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serum liver enzyme elevations occurred in up to 10% of patients on flavocoxid therapy although elevations above 3 times the upper limit of normal occurred in only 1-2% of recipients. Since its release, however, there have been several reports of clinically apparent acute liver injury attributed to

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LxA4 and LxB4 are members of the specialized pro-resolving mediators class of polyunsaturated fatty acid metabolites. They form later than the ALOX5-derived chemotactic factors in the inflammatory response and are thought to limit or resolve these responses by, for example, inhibiting the entry of

2154:. It inhibits COX-1, COX-2, and ALOX5 in vitro and in animal models. Flavocoxid has been approved for use as a medical food in the United States since 2004 and is available by prescription for use in chronic osteoarthritis in tablets of 500 mg under the commercial name Limbrel. However, in 1760:

cells that were directly implanted into their lungs; this result differs from many in vitro studies which implicated human ALOX5 along with certain of its metabolites with promoting cancer cell growth in that it finds that mouse Alox5 and, perhaps, certain of its metabolites inhibit cancer cell

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on leukocytes. Rises in cytosolic Ca, ALOX5's movement to membranes, and ALOX5's interaction with FLAP are critical to the physiological activation of the enzyme. Serine 271 and 663 phosphorylations do not appear to alter ALOX5's activity. Serine 523 phosphorylation (which is conducted by PKA)

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Sub-human mammalian Alox5 enzymes like those in rodents appear to have, at least in general, similar structures, distributions, activities, and functions as human ALOX5. Hence, model Alox5 studies in rodents appear to be valuable for defining the function of ALOX5 in humans (see

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made by ALOX5. The binding of ALOX5 to membranes as well as its interaction with FLAP likewise cause the enzyme to alter its relative levels of hydroperoxy versus epoxide production, in these cases favoring the production of the epoxide products. The presence of certain

1746:(SPMs), at least in certain rodent inflammation-based model systems. These genetic studies allow that ALOX5 along with the chemotactic factors and SPMs that they contribute to making may play similar opposing pro-inflammatory and anti-inflammatory functions in humans. 1171:

thereby becomes suited for high metabolic activity. These events, along with rises in cytosolic Ca levels, which promote the translocation of ALOX5 form the cytoplasm and nucleoplasm to the cited membranes, are induced by cell stimulation such as that caused by

2215:, one of the bioactive boswellic acids found in Boswellia serrata (Indian Frankincense) has been found to inhibit 5-lipoxygenase. Boswellia reduces brain edema in patients irradiated for brain tumor and it's believed to be due to 5-lipoxygenase inhibition. 764:

Aberrant expression of LOX5 is seen in various types of human cancer tumors in vivo as well as in various types of human cancer cell lines in vitro; these tumors and cell lines include those of the pancreas, prostate and colon. ALOX5 products, particularly

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which contributes to mediating the actions of LTC4, LTD4, and LTE4. These drugs are in common use as prophylaxis and chronic treatment of allergic and non-allergic asthma and rhinitis diseases and also may be useful for treating acquired childhood

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It may also contribute to hypersensitivity responses of the respiratory system to cold air and possibly even alcohol beverages. These pathological responses likely involve the same ALOX5-formed metabolites as those promoting allergic reactions.

1518:-eicosatrienoic acid) is identical to AA except that has a single rather than double bond between its 14 and 15 carbon. ALOX5 metabolizes mead acid to 3-series (i.e. containing 3 double bonds) analogs of its 4-series AA metabolites viz., 5( 1295:

ALOX5 metabolizes various omega-3 and omega-6 PUFA to a wide range of products with varying and sometimes opposing biological activities. A list of these substrates along with their principal metabolites and metabolite activities follows.

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to the sites of implantation. This striking difference between human in vitro and mouse in vivo studies may reflect species differences, in vitro versus in vivo differences, or cancer cell type differences in the function of ALOX5/Alox5.

1419:, i.e. they recruit and further activate circulating blood neutrophils and monocytes to sites of microbial invasion, tissue injury, and foreign bodies. When produced in excess, however, they may contribute to a wide range of pathological 2304:. These variants are associated with reduced levels of ALOX5 as well as reduced production of LTC4 in their eosinophils. These data suggest that ALOX5 may contribute to dampening the severity of asthma, possibly by metabolizing PUFA to 3052:

O'Flaherty JT, Rogers LC, Paumi CM, Hantgan RR, Thomas LR, Clay CE, High K, Chen YQ, Willingham MC, Smitherman PK, Kute TE, Rao A, Cramer SD, Morrow CS (October 2005). "5-Oxo-ETE analogs and the proliferation of cancer cells".

7098: 6124: 6114: 2332:) have been associated with the presence of asthma in single population studies. These studies suggest genetic variants may play a role, albeit a relatively minor one, in the overall susceptibility to allergic asthma. 2410:-1708 G>A is associated with NSAID-induced asthma in Korean patients and three SNP ALOX5 variants, rs4948672, rs1565096, and rs7894352, are associated with NSAID-induced cutaneous reactions in Spanish patients. 1462:

by contracting these airways and promoting in these airways inflammation, micro-vascular permeability, and mucus secretion; they likewise contribute to various allergic and non-allergic reactions involving

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Ahmad S, Thulasingam M, Palombo I, Daley DO, Johnson KA, Morgenstern R, Haeggström JZ, Rinaldo-Matthis A (2015). "Trimeric microsomal glutathione transferase 2 displays one third of the sites reactivity".

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gene promoter in 470 subjects (non-Hispanic whites, 55.1%; Hispanics, 29.6%; Asian or Pacific Islander, 7.7&; African Americans, 5.3%, and others, 2.3%) were positively associated with the severity of

2347:(NSAID) can cause NSAID-exacerbated diseases (N-ERD). These have been recently classified into 5 groups 3 of which are not caused by a classical immune mechanism and are relevant to the function of ALOX5: 6676: 6648: 6519: 3898:

Oussalah A, Mayorga C, Blanca M, Barbaud A, Nakonechna A, Cernadas J, Gotua M, Brockow K, Caubet JC, Bircher A, Atanaskovic M, Demoly P, K Tanno L, Terreehorst I, Laguna JJ, Romano A, Guéant JL (2016).

1218:) in particular mediates many instances of stimulus-induced release of PUFA in inflammatory cells. For example, chemotactic factors stimulate human neutrophils to raise cytosolic Ca which triggers cPLA 673:. A novel Sp1-binding site occurs close to the major transcription start site (position – 65); a GC-rich core region including the Sp1/Egr-1 sites may be critical for basal 5-LO promoter activity. 1661:

gene have given seemingly paradoxical results. In mice, for example, Alox5 overexpression may decrease the damage caused by some types yet increase the damage caused by other types of invasive

2427:, as judged by carotid intima–media thickness measurements. Variant alleles involved deletions (one or two) or additions (one, two, or three) of Sp1 motifs to the five tandem motifs allele. 3482: 1761:

growth. Studies in this model suggest that Alox5, acting through one or more of its metabolites, reduces growth and progression of the Lewis carcinoma by recruiting cancer-inhibiting CD4+

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extent 5-HETE stimulate human cell lines derived from these cancers to proliferate; and the pharmacological inhibition of ALOX5 in these human cell lines causes them to die by entering

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circulating leukocytes into inflamed tissues, inhibiting the pro-inflammatory action of the leukocytes, promoting leukocytes to exit from inflammatory sites, and stimulating leukocyte

773:, promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors. 2259:

as single drug therapy for persistent asthma, particularly in patients with airway obstruction. As a second drug added to corticosteroids, leukotriene inhibitors appear inferior to

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Ishii S, Noguchi M, Miyano M, Matsumoto T, Noma M (1992). "Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase".

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in clinical trials for the treatment of rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Zileuton is currently undergoing a phase II study for the treatment of

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Santos PC, Santos DA, Ribeiro LS, Fagundes CT, de Paula TP, Avila TV, Baltazar Lde M, Madeira MM, Cruz Rde C, Dias AC, Machado FS, Teixeira MM, Cisalpino PS, Souza DG (2013).

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Other factors are known to regulate ALOX5 activity in vitro but have not been fully integrated into its physiological activation during cell stimulation. ALOX5 binds with the

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VanderNoot VA, Fitzpatrick FA (1995). "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2".

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Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library".

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Barros R, Moreira A, Padrão P, Teixeira VH, Carvalho P, Delgado L, Lopes C, Severo M, Moreira P (2015). "Dietary patterns and asthma prevalence, incidence and control".

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While only one ALOX5-inhibiting drug has proven useful for treating human diseases, other drugs that act down-stream in the ALOX5-initiated pathway are in clinical use.

535: 5888: 1385:) by cell surface-attached gamma-glutamyltransferase and dipeptidase peptidase enzymes. In another pathway, ALOX5 may act in series with a second lipoxygenase enzyme, 2573:

Anwar Y, Sabir JS, Qureshi MI, Saini KS (2014). "5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical and pharmacological regulation".

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totally inactivates the enzyme and prevents its nuclear localization; stimuli which cause cells to activate PKA can thereby block production of ALOX5 metabolites.

6839: 5683: 2905:"Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid" 6775: 1738:

injury. These studies indicate that Alox5 can serve a protective function presumably by generating metabolites such as chemotactic factors that mobilize the

6638: 6562: 4430:"Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial" 1742:

system. However, the suppression of inflammation appears also to be a function of Alox5, presumably by contributing to the production of anti-inflammatory

7010: 2391:

NSAIDs-induced urticaria/angioedema (NIUA) (i.e. wheals and/or angioedema symptoms occurring shortly after NSAID ingestion in patients with no history of

1720:-null mice exhibit a worsened inflammatory component, failure to resolve inflammation-related responses, and decreased survival in experimental models of 4282:

Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O (Dec 2002). "Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase".

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within its C2-like domain; this domain, by analogy to other PLAT domain-bearing proteins, may serve as a mobile lid over ALOX5's substrate-binding site

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Hammarberg T, Reddy KV, Persson B, Rådmark O (2002). "Calcium Binding to 5-Lipoxygenase". In Honn KV, Marnett LJ, Nigam S, Dennis E, Serhan C (eds.).

1226:α), to move from its normal residence in the cytosol to cellular membranes. This chemotactic factor stimulation concurrently causes the activation of 6129: 5992: 5966: 4477:

Kar M, Altıntoprak N, Muluk NB, Ulusoy S, Bafaqeeh SA, Cingi C (2016). "Antileukotrienes in adenotonsillar hypertrophy: a review of the literature".

5225:"5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins" 2772:

Wykle RL, Wijkander J, Nixon AB, Daniel LW, O'Flaherty JT (1996). "Activation of 85 kDa PLA2 by Eicosanoids in Human Neutrophils and Eosinophils".

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as well as a wide range of other biologically active products. ALOX5 is a current target for pharmaceutical intervention in a number of diseases.

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Blazevic T, Schaible AM, Weinhäupl K, Schachner D, Nikels F, Weinigel C, Barz D, Atanasov AG, Pergola C, Werz O, Dirsch VM, Heiss EH (Mar 2014).

3756:"Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment" 6733: 6580: 5881: 4908:"Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase" 1635: 1583: 6713: 3137:

Ding XZ, Tong WG, Adrian TE (2003). "Multiple signal pathways are involved in the mitogenic effect of 5(S)-HETE in human pancreatic cancer".

554: 6567: 6336: 6316: 6311: 6301: 6281: 6266: 6256: 6065: 6035: 6010: 3333:

Maaløe T, Schmidt EB, Svensson M, Aardestrup IV, Christensen JH (Jul 2011). "The effect of n-3 polyunsaturated fatty acids on leukotriene B

1843:-HETE, which serve to attract and otherwise activate inflammation-inducing cells such as circulating leukocytes and tissue macrophages and 5287:

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides".

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Rådmark O, Werz O, Steinhilber D, Samuelsson B (2015). "5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease".

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variants for this five repeat promoter region in a study of 624 asthmatic children in Ankara, Turkey were much more likely to have severe

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gene knockout mice exhibited a decrease in the number of neutrophils and an increase in the number of bacteria that accumulated in their

6600: 6524: 6414: 6409: 6326: 6296: 6251: 6246: 6241: 6060: 6050: 6045: 6040: 2324:), or are the cellular receptors responsible for mediating the cellular responses to the down-stream ALOX products LTC4 and LTD4 (i.e. 5526: 3650:

Canavaci AM, Sorgi CA, Martins VP, Morais FR, de Sousa ÉV, Trindade BC, Cunha FQ, Rossi MA, Aronoff DM, Faccioli LH, Nomizo A (2014).

6738: 6509: 6351: 6321: 6070: 5874: 5170:

Janssen-Timmen U, Vickers PJ, Wittig U, Lehmann WD, Stark HJ, Fusenig NE, Rosenbach T, Rådmark O, Samuelsson B, Habenicht AJ (1995).

1397:). GPXs, 5-HEDH, LTA4H, LTC4S, ABCC1, and cell surface peptidases may act similarly on the ALOX5-derived metabolites of other PUFA. 6984: 6950: 6723: 6671: 6633: 6605: 6504: 6494: 6286: 547: 3597:

Fahel JS, de Souza MB, Gomes MT, Corsetti PP, Carvalho NB, Marinho FA, de Almeida LA, Caliari MV, Machado FS, Oliveira SC (2015).

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LTC4, LTD4, and LTE4 which promote vascular permeability, contract airways smooth muscle, and otherwise perturb these tissues and

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that contribute to the resolution of inflammation, promote tissue healing, and reduce the perception of inflammation-based pain.

1249:-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to stabilize ALOX5 by acting as a 5669: 5135:

Jakobsson PJ, Shaskin P, Larsson P, Feltenmark S, Odlander B, Aguilar-Santelises M, Jondal M, Biberfeld P, Claesson HE (1995).

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Rossi AG, O'Flaherty JT (1991). "Bioactions of 5-hydroxyicosatetraenoate and its interaction with platelet-activating factor".

498: 7117: 5446:"Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes" 2193:, is also described as selective ALOX5 inhibitor effective in a range of cell-free and cell-based model systems. In addition, 1911:

LTB4 and possibly 5-oxo-ETE which are chemotactic factors for, and activators of, the cell type promoting such reactions, the

7485: 4859: 2789: 2435: 1985: 2865:

Romano M, Cianci E, Simiele F, Recchiuti A (2015). "Lipoxins and aspirin-triggered lipoxins in resolution of inflammation".

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however, ALOX5 also contributes to the development and progression of excessive and chronic inflammatory responses such as:

5532: 5411:"Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence" 4319:"Indirubin-3'-monoxime exerts a dual mode of inhibition towards leukotriene-mediated vascular smooth muscle cell migration" 3901:"Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review" 2344: 5318:"5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes" 1264: 1186: 7078: 5559: 4221: 2305: 1743: 1646: 1591: 1488: 3291:"BLT2 is a pro-tumorigenic mediator during cancer progression and a therapeutic target for anti-cancer drug development" 1990:

The tissue, animal model, and animal and human genetic studies cited above implicate ALOX5 in a wide range of diseases:

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lipoxin and resolvin subfamily of SPMs which tend to inhibit these cells as well as the overall inflammatory responses.

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s to release PUFA esterified to membrane phospholipids to FLAP which then presents them to ALOX5 for their metabolism.

1215: 1103:. To varying extents, the other PUFA substrates of ALOX5 follow similar metabolic pathways to form analogous products. 7159: 5811: 2313: 1346: 1164: 967:), or, alternatively, further metabolized by ALOX5's epoxidase (also termed LTA4 synthase) activity which converts 5 855:-rich region (residues 566–577), sometimes termed a SH3-binding domain, which promotes its binding to proteins with 6918: 6424: 6361: 6188: 6109: 2235: 2166: 1932: 1590:

the pro-inflammatory and pro-allergic activities of their arachidonic acid-derived counterparts. RvE1 and ReV2 are

1353:(5-oxo-ETE). Alternatively, the intrinsic activity of ALOX5 may convert 5-HpETE to its 5,6 epoxide, leukotriene A4 1227: 1128: 1475:. Certain of these peptide-leukotrienes have been shown to promote the growth of cultured human breast cancer and 492: 6104: 5961: 633:(kb) on chromosome 10 (all other human lipoxygenases are clustered together on chromosome 17), is composed of 14 6758: 1337:) which is then rapidly converted to physiologically and pathologically important products. Ubiquitous cellular 1238:

isoforms using other kinases which phosphorylate them on different serine residues). These two events allow cPLA

6174: 6119: 5661: 5552: 2399: 2309: 2110:

However, clinical use of drugs that inhibit ALOX5 to treat any of these diseases has been successful with only

1404: 1342: 766: 479: 474: 7315: 7068: 5834: 3754:

Poczobutt JM, Nguyen TT, Hanson D, Li H, Sippel TR, Weiser-Evans MC, Gijon M, Murphy RC, Nemenoff RA (2016).

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receptors have also been shown to promote the growth of various types of human cancer cell lines in culture.

1704:. On the other hand, ALOX5 gene knockout mice demonstrate an enhanced resistance and lessened pathology to 826:

which promotes its binding to ligand substrates, Ca, cellular phospholipid membranes, Coactin-like protein (

7044: 7030: 6977: 6943: 6658: 6620: 5779: 5544: 1674:

mice are more susceptible to the development and pathological complications of experimental infection with

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O'Flaherty JT, Kuroki M, Nixon AB, Wijkander J, Yee E, Lee SL, Smitherman PK, Wykle RL, Daniel LW (1996).

467: 7083: 7039: 1721: 1408: 1350: 770: 1645:(i.e. RvD1, RvD2, RvD3, RvD4, RvD5, RvD6, AT-RVD1, AT-RVD2, AT-RVD3, AT-RVD4, AT-RVD5, and AT-RVD6) are 7430: 5515: 5316:

Woods JW, Evans JF, Ethier D, Scott S, Vickers PJ, Hearn L, Heibein JA, Charleson S, Singer II (1993).

3240:

Bäck M, Powell WS, Dahlén SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE (2014).

2018: 1920: 1817: 1181: 6903: 5049:"Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187" 7480: 7416: 7403: 7390: 7377: 7364: 7351: 7338: 7300: 7053: 6085: 5942: 5767: 4178:

Cingi C, Muluk NB, Ipci K, Şahin E (2015). "Antileukotrienes in upper airway inflammatory diseases".

1433: 1092: 1048: 864: 495: 5258:

Shaw KJ, Ng C, Kovacs BW (1994). "Cyclooxygenase gene expression in human endometrium and decidua".

419: 7310: 7264: 7207: 7001: 6849: 6817: 6696: 5839: 5822: 5774: 5519: 4750: 4732: 3942:"5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes" 2418:

Bearers of two variations in the predominant five tandem repeat Sp1 binding motif (GGGCCGG) of the

2321: 2293: 2260: 2131: 1362: 1004: 666: 387: 3090:"Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling" 2135: 7212: 6970: 6785: 6595: 5928: 5911: 5829: 5640: 3530:"The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis" 3088:

Avis IM, Jett M, Boyle T, Vos MD, Moody T, Treston AM, Martínez A, Mulshine JL (February 1996).

1119:

ALOX5 exists primarily in the cytoplasm and nucleoplasm of cells. Upon cell stimulation, ALOX5:

665:. Five of the 8 GC boxes are arranged in tandem and are recognized by the transcription factors 5793: 2351:

NSAIDs-exacerbated respiratory disease (NERD), i.e. symptoms of bronchial airways obstruction,

2028: 1412: 1338: 1108: 940: 845: 4770:"Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis" 4428:

Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K, et al. (August 2011).

3381:"The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution" 2189:

in inhibiting ALOX5. Indirubin-3'-monoxime, a derivative of the naturally occurring alkaloid,

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cell lines thereby suggesting that ALOX5 may contribute to the progression of these diseases.

1423:(5-HETE and LTB4). 5-Oxo-ETE is a particularly potent chemotactic factor for and activator of 7233: 7152: 5917: 5786: 5730: 5583: 3991:"Lipid Mediators of Allergic Disease: Pathways, Treatments, and Emerging Therapeutic Targets" 3341:

production from stimulated neutrophil granulocytes in patients with chronic kidney disease".

2048: 1864: 1676: 1547: 1458:, certain non-allergic hypersensitivity airways reactions, and other lung diseases involving 1420: 1156: 455: 6962: 4846:. Advances in Experimental Medicine and Biology. Vol. 507. Springer. pp. 117–121. 3900: 7475: 7460: 7305: 7073: 7063: 6898: 6544: 5650: 5183: 5095: 5007: 4954: 4826: 3435:

Qu Q, Xuan W, Fan GH (2015). "Roles of resolvins in the resolution of acute inflammation".

2466: 2182: 2008: 1952: 1807: 1757: 1682: 1607: 1194:, in order to form biologically active products. This is accomplished by a large family of 781: 610: 431: 4714: 3848:"Specialized pro-resolving mediators: endogenous regulators of infection and inflammation" 392: 8: 7465: 7269: 5538: 4410:

Antiödematöse Wirkung von Boswellia serrata auf das Strahlentherapie-assoziierte Hirnödem

2352: 2285: 2252: 2231: 2210: 2186: 1459: 1250: 399: 5187: 5099: 5011: 4958: 4415:

Anti-edematous effect of Boswellia serrata on radiation therapy – associated brain edema

4368:"5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy" 3206: 3181: 2470: 7202: 7126: 7088: 5903: 5635: 5342: 5317: 5153: 5136: 4844:

Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5

4696: 4647: 4622: 4598: 4573: 4546: 4521: 4502: 4459: 4343: 4318: 4256: 4203: 4107: 4082: 4063: 4015: 3990: 3971: 3872: 3847: 3828: 3780: 3755: 3731: 3706: 3682: 3651: 3627: 3598: 3556: 3529: 3510: 3460: 3405: 3380: 3307: 3290: 3266: 3241: 3219: 3162: 3029: 3004: 2929: 2904: 2839: 2814: 2673: 2660: 2023: 1936: 1822: 1543: 1310: 939:-HpETE intermediate may then be released by the enzyme and rapidly reduced by cellular 753:

express low levels of ALOX5. Up-regulation of ALOX5 may occur during the maturation of

59: 5492: 5359:

Mancini JA, Li C, Vickers PJ (1993). "5-Lipoxygenase activity in the human pancreas".

5241: 5224: 5118: 5083: 5065: 5048: 5030: 4995: 4924: 4907: 4295: 3114: 3089: 2586: 2489: 2454: 2123: 1091:-eicosatetraenoic acid). The Glu and Gly residues of LTC4 may be removed step-wise by 510: 56: 6552: 5496: 5467: 5432: 5397: 5368: 5347: 5304: 5300: 5275: 5271: 5246: 5211: 5206: 5171: 5158: 5137:"Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes" 5123: 5070: 5035: 4982: 4977: 4942: 4929: 4894: 4890: 4865: 4855: 4830: 4791: 4688: 4652: 4603: 4551: 4494: 4451: 4389: 4348: 4299: 4195: 4160: 4112: 4055: 4020: 3963: 3922: 3877: 3820: 3785: 3736: 3687: 3632: 3561: 3502: 3452: 3410: 3358: 3312: 3271: 3211: 3154: 3119: 3070: 3034: 2978: 2934: 2882: 2844: 2795: 2785: 2754: 2704: 2642: 2590: 2542: 2494: 2396: 2392: 2384: 2037: 1829: 1730: 1712: 662: 486: 37: 4700: 4506: 4463: 4207: 4067: 3975: 3514: 3464: 3166: 2735:"Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease" 1896: 1787:

by contributing to the mounting inflammatory responses to a wide range of diseases:

1234:α by phosphorylating it on ser-505 (other cell types may activate this or other cPLA 776:

Studies with cultured human cells have found that there are a large number of ALOX5

7470: 7248: 7243: 7217: 7145: 6913: 6470: 5866: 5718: 5696: 5602: 5488: 5457: 5422: 5389: 5337: 5329: 5296: 5267: 5236: 5201: 5191: 5148: 5113: 5103: 5060: 5025: 5015: 4972: 4962: 4919: 4886: 4847: 4822: 4781: 4680: 4642: 4634: 4593: 4585: 4541: 4533: 4486: 4441: 4379: 4338: 4330: 4291: 4187: 4150: 4102: 4094: 4047: 4010: 4002: 3953: 3912: 3867: 3859: 3832: 3812: 3775: 3767: 3726: 3718: 3677: 3667: 3622: 3614: 3551: 3541: 3494: 3444: 3400: 3392: 3350: 3302: 3261: 3253: 3223: 3201: 3193: 3146: 3109: 3101: 3062: 3024: 3016: 2968: 2924: 2916: 2874: 2834: 2826: 2777: 2746: 2696: 2634: 2582: 2532: 2484: 2474: 2356: 1766: 1706: 1314: 1195: 1152: 1140: 1136: 872: 801: 750: 4251: 3020: 2776:. Advances in Experimental Medicine and Biology. Vol. 416. pp. 327–331. 1999: 1796: 871:

The enzyme possesses two catalytic activities as illustrated by its metabolism of

7295: 7279: 7192: 5725: 5575: 4851: 4768:

Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M (2004).

4638: 4623:"DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation" 4537: 3546: 3498: 3066: 2920: 2878: 2781: 2700: 2638: 2424: 2169:, and atherosclerosis (NCT00404313, NCT00418613, and NCT00421278, respectively). 2013: 1844: 1812: 1784: 1739: 1575: 738: 690: 5691: 3722: 3579: 3354: 2383:

responses occurring shortly after NSAID ingestion in patients with a history of

1055:), which bind the sulfur of cysteine's thio (i.e. SH) residue in the tripeptide 514: 7444: 7333: 7274: 6993: 6923: 6443: 6396: 6388: 6380: 6223: 6215: 6207: 6137: 5974: 5900: 5748: 5579: 4589: 4098: 3958: 3941: 3396: 2973: 2956: 2459:

Proceedings of the National Academy of Sciences of the United States of America

2376: 2368: 2256: 2165:(MK-0633) has completed a Phase II clinical trial for the treatment of asthma, 2155: 2060: 1958: 1877: 1839:

potent chemotactic factor, LTB4, and possibly also weaker chemotactic factor, 5

1571: 1468: 1255: 1008: 823: 718: 530: 4490: 4229: 4191: 4006: 3197: 2830: 2106:

the progression of certain cancers such as those of the prostate and pancreas.

7454: 7238: 7197: 6893: 4813:

Rådmark OP (2000). "The molecular biology and regulation of 5-lipoxygenase".

3771: 3242:"Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7" 2119: 1762: 1671: 1370: 1044: 746: 646: 505: 5574: 5427: 5410: 5196: 4967: 7187: 7020: 6728: 6514: 5645: 5393: 5333: 4994:

Matsumoto T, Funk CD, Rådmark O, Höög JO, Jörnvall H, Samuelsson B (1988).

4869: 4834: 4795: 4692: 4656: 4607: 4555: 4498: 4455: 4393: 4352: 4303: 4199: 4164: 4116: 4059: 4024: 3926: 3881: 3789: 3740: 3691: 3636: 3565: 3506: 3483:"n-3 Fatty acid supplementation and proresolving mediators of inflammation" 3456: 3414: 3362: 3316: 3275: 3215: 3158: 3074: 3038: 2982: 2938: 2886: 2848: 2758: 2708: 2646: 2594: 2546: 2479: 1725: 1586:

for further details on this metabolism) viz., resolvin E1 (RvE1) and RvE2.

1191: 880: 722: 682: 606: 5500: 5471: 5436: 5401: 5372: 5351: 5308: 5279: 5250: 5215: 5172:"Expression of 5-lipoxygenase in differentiating human skin keratinocytes" 5162: 5127: 5108: 5074: 5039: 4986: 4933: 4898: 4526:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

4384: 4367: 3967: 3824: 3672: 3123: 3055:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

2909:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

2799: 2627:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

2498: 2245:

Acquired non-inflammatory myopathy § Diet and Trauma Induced Myopathy

2173:

has completed phase II studies for the treatment of asthma (NCT00723021).

2138:). Given these deficiencies, other drugs targeting ALOX5 are under study. 443: 360: 7411: 7346: 7182: 6908: 6557: 6346: 6291: 5897: 5803: 5630: 5614: 5609: 5020: 4786: 4769: 4417:] (Ph.D. thesis) (in German). Breisgau, Germany: University Freiburg. 4334: 3618: 2240: 2223: 2219: 2146:

is a proprietary blend of purified plant derived bioflavonoids including

876: 838: 734: 614: 5462: 5445: 7107: 6865: 6802: 6539: 6331: 6306: 5740: 5700: 5692: 5082:

Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA (1988).

4446: 4429: 4155: 4138: 3863: 3816: 3448: 2537: 2520: 2380: 2360: 2297: 2227: 2177: 2142: 2094: 1968: 1963: 1940: 1912: 1701: 1594:

that contribute to the resolution of inflammation and other reactions.

1424: 1416: 1184:(PUFA) substrates, which commonly are bound in an ester linkage to the 1173: 856: 820: 813: 797: 742: 710: 698: 694: 642: 6581: 5478: 4684: 4268: 4051: 3917: 3257: 3150: 3105: 2750: 2363:

occurring shortly after NSAID ingestion in patients with a history of

903:-eicosatetraenoic acid) at carbon 5 of its 1,4 diene group (i.e. its 5 7385: 7359: 6997: 6718: 6643: 6534: 6499: 2190: 2122:(mild-to-moderate inflammatory facial acne) and a phase I study (see 2099: 1503: 1484: 1472: 1429: 1290: 1132: 1056: 754: 714: 630: 75: 63: 52: 2734: 2453:

Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B (Apr 1989).

1919:-HETE, also act synergistically with another pro-allergic mediator, 197: 193: 7439: 6870: 6834: 6748: 6681: 6572: 6529: 6236: 6025: 5597: 4996:"Molecular cloning and amino acid sequence of human 5-lipoxygenase" 4139:"Recent advances in the search for novel 5-lipoxygenase inhibitors" 3988: 2202: 2198: 2194: 2151: 2147: 2127: 2111: 2055: 1995: 1872: 1835:

These dual functions probably reflect ALOX5's ability to form the:

1792: 1662: 1642: 1579: 1464: 1060: 726: 706: 702: 654: 349: 5169: 4905: 4408: 4316: 3939: 5134: 2340: 2329: 2325: 2044: 1860: 1492: 1390: 1298: 1246: 1064: 972: 852: 848:(ATP) binding site; ATP is crucial for ALOX5's metabolic activity 793: 686: 658: 462: 179: 138: 3051: 2624: 1636:

Specialized pro-resolving mediators § DHA-derived resolvins

1584:

Specialized pro-resolving mediators § EPA-derived resolvins

1333:-eicosatetraenoic acid), to 5-hydroperoxyeicosatetraenoic acid ( 7398: 7168: 7048: 7034: 6807: 6610: 6464: 5704: 3332: 3005:"The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor" 2364: 2301: 2075: 2065: 1892: 1882: 1735: 1657:

Studies in model animal systems that delete or overexpress the

1603: 1455: 1386: 1163:

is able to accept substrate fatty acids presented to it by the

1124: 964: 730: 650: 638: 595: 542: 438: 426: 414: 327: 97: 5408: 4671:

of hypersensitivity to nonsteroidal anti-inflammatory drugs".

4255:

for "The Effect of MK0633 in Patients With Chronic Asthma" at

7372: 6992: 5758: 5753: 4841: 4281: 2689:

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

2114:

along with its controlled released preparation, Zileuton CR.

1693: 1432:. ALOX5 and its LTB4 metabolite as well as this metabolite's 1374: 1287:-glycerol increase the catalytic activity of ALOX5 in vitro. 1180:

In addition to its activation, ALOX5 must gain access to its

1052: 831: 670: 4943:"Characterization of the human 5-lipoxygenase gene promoter" 4228:. United States National Library of Medicine. Archived from 3897: 2864: 2685: 1357:, which is then either rapidly converted to leukotriene B4 ( 1273: 4876: 4037: 3989:

Schauberger E, Peinhaupt M, Cazares T, Lindsley AW (2016).

3527: 2312:

differences in the genes that promote ALOX5 activity (i.e.

2276:

gene may vary with the population and individuals studied.

2070: 1887: 1451: 1447: 1443: 1437: 1400: 1382: 1378: 1366: 1358: 1354: 1216:

Phospholipase A2 § Cytosolic phospholipases A2 (cPLA2)

1144: 1100: 1096: 1000: 860: 827: 777: 634: 602: 591: 450: 7137: 4906:

Nguyen T, Falgueyret JP, Abramovitz M, Riendeau D (1991).

4574:"Genetics and pharmacogenetics of the leukotriene pathway" 3649: 3596: 2452: 2292:

gene commonly possess five GGGCCGG repeats which bind the

1578:

enzymes in serial metabolic pathways to metabolize EPA to

5443: 4669: 4476: 3656:

infection is attenuated in 5-lipoxygenase-deficient mice"

3599:"5-Lipoxygenase negatively regulates Th1 response during 3130: 2771: 1341:(GPXs) reduce 5-HpETE to 5-hydroxyeicosatetraenoic acid ( 1003:). LTA4 is then acted on by a separate, soluble enzyme, 805: 6425: 6362: 6189: 5409:

Brock TG, McNish RW, Bailie MB, Peters-Golden M (1997).

4993: 4940: 4522:"Mammalian lipoxygenases and their biological relevance" 4427: 2774:

Platelet-Activating Factor and Related Lipid Mediators 2

2296:

and thereby increase the gene's transcription of ALOX5.

1859:

ALOX5 contributes to the development and progression of

609:

family of enzymes. It transforms essential fatty acids (

3753: 3343:

Prostaglandins, Leukotrienes, and Essential Fatty Acids

2335: 1998:, trauma, burns, and other forms of tissue injury (see 645:(kDa) ALOX5 protein consisting of 673 amino acids. The 6586:

Tooltip Arachidonate 5-lipoxygenase-activating protein

6175: 5081: 3239: 2572: 7428: 5379: 5315: 4519: 3704: 3045: 6759: 6659: 6621: 5896: 4767: 4365: 2518: 2082:

NSAID-induced acute non-allergic reactions such as:

1373:(LTC4S); LTC4 exits its cells of origin through the 1230:(MAPK) which in turn stimulates the activity of cPLA 6482: 4177: 3802: 3707:"Lipid mediators in the resolution of inflammation" 2455:"Characterization of the human 5-lipoxygenase gene" 1923:, to stimulate and otherwise activate eosinophils. 1634:-docosahexaenoic acid), to D series resolvins (see 1395:

Specialized pro-resolving mediators § Lipoxins

1147:, and/or a Ca/calmodulin-dependent protein kinase; 5444:Nassar GM, Montero A, Fukunaga M, Badr KF (1997). 4751:"Reference SNP (refSNP) Cluster Report: rs7894352" 4733:"Reference SNP (refSNP) Cluster Report: rs1565096" 4715:"Reference SNP (refSNP) Cluster Report: rs4948672" 4143:Basic & Clinical Pharmacology & Toxicology 4136: 2525:Basic & Clinical Pharmacology & Toxicology 2375:NSAIDs-exacerbated cutaneous disease (NECD), i.e. 1291:Substrates, metabolites, and metabolite activities 6086: 5943: 5222: 4400: 3378: 2728: 2726: 2724: 2722: 2720: 2718: 1756:in the lung tumor volume and liver metastasis of 1454:contribute to allergic airways reactions such as 1167:(FLAP) which is embedded in these membranes; and 661:and thus resembles the gene promoters of typical 605:. Arachidonate 5-lipoxygenase is a member of the 598:(EC 1.13.11.34) that in humans is encoded by the 7452: 6850: 6818: 6697: 5358: 3289:Cho NK, Joo YC, Wei JD, Park JI, Kim JH (2013). 3087: 1067:to carbon 6 of LTA4 thereby forming LTC4 (i.e. 5 863:and may thereby link the enzyme's regulation to 759:granulocyte macrophage colony-stimulating factor 6786: 5929: 4571: 4567: 4565: 4132: 4130: 4128: 4126: 3893: 3891: 3476: 3474: 3430: 3428: 3426: 3424: 3374: 3372: 3235: 3233: 2998: 2996: 2994: 2992: 2957:"The role of leukotrienes in allergic diseases" 2950: 2948: 2898: 2896: 2860: 2858: 761:and then stimulated with physiological agents. 5286: 5084:"Cloning of the cDNA for human 5-lipoxygenase" 4578:The Journal of Allergy and Clinical Immunology 3705:Serhan CN, Chiang N, Dalli J, Levy BD (2015). 3328: 3326: 3136: 2732: 2715: 2620: 2618: 2616: 2614: 2612: 2610: 2608: 2606: 2604: 2568: 2566: 2564: 2562: 2560: 2558: 2556: 2514: 2512: 2510: 2508: 2136:Zileuton § Contraindications and warnings 7153: 6978: 5882: 5677: 5560: 5046: 3480: 3288: 2316:), metabolize the initial product of ALOX5, 5 1926: 5257: 4761: 4663: 4614: 4562: 4513: 4470: 4421: 4359: 4310: 4275: 4171: 4123: 4080: 4074: 4031: 3982: 3888: 3839: 3747: 3698: 3643: 3590: 3521: 3471: 3421: 3369: 3282: 3230: 3182:"Survival regulation of leukemia stem cells" 3173: 3002: 2989: 2945: 2902: 2893: 2855: 2806: 1710:infection and, at least in its acute phase, 4941:Hoshiko S, Rådmark O, Samuelsson B (1990). 3933: 3796: 3323: 2954: 2812: 2679: 2601: 2553: 2505: 1783:Studies implicate ALOX5 in contributing to 1283:-glycerol but not 1-stearoyl-2-arachidonyl- 7160: 7146: 6985: 6971: 6919:5-HPETE (arachidonic acid 5-hydroperoxide) 5889: 5875: 5684: 5670: 5567: 5553: 5260:Prostaglandins Leukot. Essent. Fatty Acids 4620: 4479:European Archives of Oto-Rhino-Laryngology 4087:Annals of Allergy, Asthma & Immunology 3711:Cold Spring Harbor Perspectives in Biology 2765: 2521:"5-lipoxygenase mRNA and protein isoforms" 2446: 5518:at the U.S. National Library of Medicine 5461: 5426: 5341: 5240: 5205: 5195: 5152: 5117: 5107: 5064: 5029: 5019: 4976: 4966: 4923: 4785: 4646: 4597: 4545: 4445: 4383: 4342: 4154: 4106: 4014: 3957: 3916: 3871: 3845: 3779: 3730: 3681: 3671: 3626: 3555: 3545: 3434: 3404: 3306: 3265: 3205: 3113: 3028: 2972: 2928: 2838: 2536: 2488: 2478: 2005:chronic inflammatory conditions such as: 1979: 1638:for further details on this metabolism). 6433:Tooltip Cysteinyl leukotriene receptor E 6370:Tooltip Cysteinyl leukotriene receptor 2 6197:Tooltip Cysteinyl leukotriene receptor 1 4520:Kuhn H, Banthiya S, van Leyen K (2015). 4366:Bishayee K, Khuda-Bukhsh AR (Sep 2013). 2519:Ochs MJ, Suess B, Steinhilber D (2014). 1903:This activity reflects its formation of 1773: 1537: 1345:); 5-HETE may be further metabolized by 1151:moves to bind with phospholipids in the 4812: 4083:"Lipid mediators and allergic diseases" 2243:due to adenotonsillar hypertrophy (see 1948:aspirin-exacerbated respiratory disease 1597: 1109:Lipoxygenase § Mouse lipoxygenases 1095:and a dipeptidase to form sequentially 681:Cells primarily involved in regulating 7453: 6180:Tooltip Cysteinyl leukotriene receptor 4827:10.1164/ajrccm.161.supplement_1.ltta-3 4406: 1915:. 5-Oxo-ETE and, to a lesser extent, 5 1606:to metabolize the omega 3 fatty acid, 757:and in human neutrophils treated with 7141: 6966: 5870: 5665: 5548: 3580:"Alox5 – arachidonate 5-lipoxygenase" 3379:Serhan CN, Chiang N, Dalli J (2015). 3094:The Journal of Clinical Investigation 2436:Arachidonate 5-lipoxygenase inhibitor 2345:non-steroidal anti-inflammatory drugs 1986:Arachidonate 5-lipoxygenase inhibitor 1652: 1043:-eicosatetraenoic acid) or by either 887:) residue to arachidonic acid (i.e. 5 6768:Tooltip Leukotriene B4 ω-hydroxylase 6664:Tooltip Arachidonate 15-lipoxygenase 6626:Tooltip Arachidonate 12-lipoxygenase 4372:Acta Biochimica et Biophysica Sinica 3186:Cellular and Molecular Life Sciences 3179: 2336:NSAID-induced non-allergic reactions 2201:, is a 5-LO inhibitor as defined by 2181:, an active constituent of the herb 1994:excessive inflammatory responses to 1377:(ABCC1) and is rapidly converted to 792:Human ALOX5 is a soluble, monomeric 7079:4-Hydroxyphenylpyruvate dioxygenase 6487:Tooltip Arachidonate 5-lipoxygenase 4774:The New England Journal of Medicine 4040:Clinical & Experimental Allergy 3295:American Journal of Cancer Research 2306:specialized pro-resolving mediators 1744:specialized pro-resolving mediators 1647:specialized pro-resolving mediators 1592:specialized pro-resolving mediators 1489:Specialized pro-resolving mediators 1304: 1222:s, particularly the α isoform (cPLA 816:catalytic domain (residues 126–673) 13: 5223:Lepley RA, Fitzpatrick FA (1994). 5154:10.1111/j.1432-1033.1995.tb20778.x 4805: 4180:Current Allergy and Asthma Reports 3995:Current Allergy and Asthma Reports 3481:Barden AE, Mas E, Mori TA (2016). 2413: 2279: 2263:drugs in the treatment of asthma. 1931:ALOX5 contributes to non-allergic 1007:, to form the dihydroxyl product, 14: 7497: 6899:γ-Linolenic acid (gamolenic acid) 6553:Meclofenamic acid (meclofenamate) 6094:Tooltip Leukotriene B4 receptor 2 5951:Tooltip Leukotriene B4 receptor 1 5812:5-Lipoxygenase activating protein 5509: 4137:Steinhilber D, Hofmann B (2014). 2587:10.2174/1389450114666131209110745 2314:5-lipoxygenase-activating protein 2266: 2209:Acetyl-keto-beta-boswellic acid ( 1897:Allergy § Signs and symptoms 1795:invasion, trauma, and burns (see 1347:5-hydroxyeicosanoid dehydrogenase 1228:mitogen-activated protein kinases 1165:5-lipoxygenase-activating protein 1129:mitogen-activated protein kinases 808:. Structurally, ALOX5 possesses: 7438: 6858:Tooltip Leukotriene D4 hydrolase 6827:Tooltip Leukotriene C4 hydrolase 6706:Tooltip Leukotriene A4 hydrolase 4627:European Journal of Pharmacology 4572:Tantisira KG, Drazen JM (2009). 3534:PLOS Neglected Tropical Diseases 2867:European Journal of Pharmacology 2819:Cardiovascular Drugs and Therapy 2236:cysteinyl leukotriene receptor 1 2167:chronic obstructive lung disease 1933:NSAID hypersensitivity reactions 1867:reactions and diseases such as: 1297: 1262:-glycerol, 1-hexadecyl-2-acetyl- 943:to its corresponding alcohol, 5( 6951:Prostanoid signaling modulators 6795:Tooltip Leukotriene C4 synthase 5934:Tooltip Leukotriene B4 receptor 4743: 4725: 4707: 4261: 4243: 4214: 3572: 3246:British Journal of Pharmacology 3081: 2815:"Phospholipase A2 biochemistry" 2733:Haeggström JZ, Funk CD (2011). 1778: 787: 2666: 2653: 2400:single-nucleotide polymorphism 2310:Single nucleotide polymorphism 1752:gene knockout mice exhibit an 1365:(LTA4H) or to leukotriene C4 ( 931:-eicosatetraenoic acid (i.e. 5 767:5-hydroxyeicosatetraenoic acid 629:gene, which occupies 71.9 kilo 1: 7069:Homogentisate 1,2-dioxygenase 6944:Receptor/signaling modulators 5835:Gamma-glutamyl transpeptidase 5823:LTA4 hydrolase (B4 synthesis) 5493:10.1016/S0378-1119(97)00411-3 5242:10.1016/S0021-9258(19)51063-8 5066:10.1016/S0021-9258(18)38066-9 5047:Rouzer CA, Kargman S (1988). 4925:10.1016/S0021-9258(18)54744-X 4879:Biochem. Biophys. Res. Commun 4815:Am. J. Respir. Crit. Care Med 4296:10.1016/s0006-2952(02)01387-4 4081:Fanning LB, Boyce JA (2013). 3487:Current Opinion in Lipidology 3021:10.1016/j.plipres.2013.09.001 2440: 2038:Inflammation § Disorders 1830:Inflammation § Disorders 1689:Paracoccidioides brasiliensis 1114: 999:-eicosatetraenoic acid (i.e. 963:-eicosatetraenoic acid (i.e. 737:are ALOX5-negative. In skin, 676: 7486:Peripheral membrane proteins 7045:Arachidonate 15-lipoxygenase 7031:Arachidonate 12-lipoxygenase 5780:Prostaglandin-E2 9-reductase 5301:10.1016/0378-1119(94)90802-8 5272:10.1016/0952-3278(94)90160-0 5176:Proc. Natl. Acad. Sci. U.S.A 5088:Proc. Natl. Acad. Sci. U.S.A 5000:Proc. Natl. Acad. Sci. U.S.A 4947:Proc. Natl. Acad. Sci. U.S.A 4891:10.1016/0006-291X(92)91901-2 4852:10.1007/978-1-4615-0193-0_19 4639:10.1016/j.ejphar.2015.11.001 4538:10.1016/j.bbalip.2014.10.002 3547:10.1371/journal.pntd.0002390 3499:10.1097/MOL.0000000000000262 3067:10.1016/j.bbalip.2005.08.009 3003:Powell WS, Rokach J (2013). 2921:10.1016/j.bbalip.2014.10.008 2903:Powell WS, Rokach J (2015). 2879:10.1016/j.ejphar.2015.03.083 2813:Burke JE, Dennis EA (2009). 2782:10.1007/978-1-4899-0179-8_52 2701:10.1016/j.bbapap.2015.06.003 2639:10.1016/j.bbalip.2014.08.012 2124:Clinical trial § Phases 1696:perforation-induced sepsis, 1498: 1477:chronic lymphocytic leukemia 1202:) enzymes. The cytosolic PLA 7: 7167: 7084:Indoleamine 2,3-dioxygenase 7040:Arachidonate 8-lipoxygenase 7026:Arachidonate 5-lipoxygenase 5816:Arachidonate 5-lipoxygenase 5516:Arachidonate+5-Lipoxygenase 4621:Duvall MG, Levy BD (2016). 3723:10.1101/cshperspect.a016311 3355:10.1016/j.plefa.2011.04.004 2430: 1722:respiratory syncytial virus 1351:5-oxo-eicosatetraenoic acid 771:5-oxo-eicosatetraenoic acid 649:region of ALOX5 contains 8 572:Arachidonate 5-lipoxygenase 377:arachidonate 5-lipoxygenase 22:arachidonate 5-lipoxygenase 10: 7502: 5537:gene details page in the 4590:10.1016/j.jaci.2009.06.035 4271:. MedKoo Biosciences, Inc. 4099:10.1016/j.anai.2013.06.031 3959:10.4049/jimmunol.157.1.336 3852:Nature Reviews. Immunology 3846:Basil MC, Levy BD (2016). 3437:Cell Biology International 3397:10.1016/j.smim.2015.03.004 3009:Progress in Lipid Research 2974:10.1016/j.alit.2014.09.001 2955:Liu M, Yokomizo T (2015). 2019:inflammatory bowel disease 2000:Inflammation § Causes 1983: 1927:Hypersensitivity reactions 1921:platelet-activating factor 1854: 1818:inflammatory bowel disease 1797:Inflammation § Causes 1602:ALOX5 acts in series with 1258:such as 1-oleoyl-2-acetyl- 1182:polyunsaturated fatty acid 7324: 7316:Michaelis–Menten kinetics 7288: 7257: 7226: 7175: 7116: 7097: 7054:Linoleate 11-lipoxygenase 7009: 6935: 6883: 6848: 6816: 6784: 6757: 6695: 6657: 6619: 6480: 6463: 6423: 6360: 6187: 6173: 6084: 5941: 5927: 5910: 5848: 5802: 5739: 5711: 5623: 5590: 4491:10.1007/s00405-016-3983-8 4192:10.1007/s11882-015-0564-7 4007:10.1007/s11882-016-0628-3 3660:Mediators of Inflammation 3198:10.1007/s00018-015-2108-7 2961:Allergology International 2831:10.1007/s10557-008-6132-9 2676:at KEGG Pathway Database. 2663:at KEGG Pathway Database. 1123:may be phosphorylated on 1093:gamma-glutamyltransferase 1049:glutathione S-transferase 865:tyrosine kinase receptors 553: 541: 529: 524: 520: 504: 485: 473: 461: 449: 437: 425: 413: 408: 398: 386: 381: 376: 364: 359: 355: 348: 326: 311: 298: 294: 279: 275: 268: 255: 251: 236: 232: 225: 214: 210: 191: 187: 178: 167: 163: 150: 146: 137: 126: 122: 109: 105: 96: 81: 74: 70: 50: 47: 42: 35: 30: 26: 21: 7208:Diffusion-limited enzyme 5520:Medical Subject Headings 4284:Biochemical Pharmacology 4222:"Flavocoxid Drug Record" 3772:10.4049/jimmunol.1501648 2322:leukotriene-A4 hydrolase 2294:Sp1 transcription factor 2261:beta2-adrenergic agonist 2255:have proven inferior to 2132:chronic myeloid leukemia 1716:infection. Furthermore, 1393:A4 (LxA4) and LxB4 (see 1363:leukotriene-A4 hydrolase 1127:663, 523, and/or 271 by 1005:leukotriene-A4 hydrolase 911:double bonds) to form 5( 741:strongly express ALOX5. 6904:Dihomo-γ-linolenic acid 5428:10.1074/jbc.272.13.8276 5197:10.1073/pnas.92.15.6966 4968:10.1073/pnas.87.23.9073 4323:Cardiovascular Research 2205:studies of the enzyme. 1339:glutathione peroxidases 1190:2 position of membrane 941:glutathione peroxidases 780:splice variants due to 641:encoding the mature 78 620: 5394:10.1006/abio.1995.1444 5334:10.1084/jem.178.6.1935 4249:Clinical trial number 3607:Infection and Immunity 3385:Seminars in Immunology 2695:(10 Pt A): 1365–1371. 2480:10.1073/pnas.86.8.2587 2320:-HpETE, to LTB4 (i.e. 1980:ALOX5-inhibiting drugs 1542:ALOX5 metabolizes the 1421:inflammatory responses 1413:innate immune response 1411:may contribute to the 1389:, to metabolize AA to 1309:ALOX5 metabolizes the 846:adenosine triphosphate 7301:Eadie–Hofstee diagram 7234:Allosteric regulation 7013:: two atoms of oxygen 6840:Serine-borate complex 6006:CGS-23131 (LY-223982) 5731:Diacylglycerol lipase 5584:Non-heme iron protein 5109:10.1073/pnas.85.2.416 3946:Journal of Immunology 3760:Journal of Immunology 2402:(SNP) variant in the 2049:allergic inflammation 1865:allergic inflammation 1774:Clinical significance 1677:Klebsiella pneumoniae 1582:of the E series (see 1548:eicosapentaenoic acid 1538:Eicosapentaenoic acid 1279:, and 1,2-dioctanoyl- 1157:endoplasmic reticulum 7311:Lineweaver–Burk plot 7101:: one atom of oxygen 7074:Cysteine dioxygenase 7064:Catechol dioxygenase 6776:17-Octadecynoic acid 6546:Hypericum perforatum 5651:Tyrosine hydroxylase 5531:genome location and 5021:10.1073/pnas.85.1.26 4787:10.1056/NEJMoa025079 3652:"The acute phase of 3619:10.1128/IAI.02592-14 2575:Current Drug Targets 2253:receptor antagonists 2232:receptor antagonists 2187:molar concentrations 2185:, is active at micro 2126:) combining it with 2009:rheumatoid arthritis 1953:nonallergic rhinitis 1808:rheumatoid arthritis 1758:Lewis lung carcinoma 1683:Borrelia burgdorferi 1608:docosahexaenoic acid 1598:Docosahexaenoic acid 1272:-hexadecyl-2-acetyl- 782:alternative splicing 6871:Ubenimex (bestatin) 6749:Ubenimex (bestatin) 5641:Iron–sulfur protein 5539:UCSC Genome Browser 5463:10.1038/ki.1997.209 5235:(39): 24163–24168. 5188:1995PNAS...92.6966J 5100:1988PNAS...85..416D 5059:(22): 10980–10988. 5012:1988PNAS...85...26M 4959:1990PNAS...87.9073H 4918:(32): 22057–22062. 4385:10.1093/abbs/gmt064 3673:10.1155/2014/893634 3180:Hu Y, Li S (2016). 2471:1989PNAS...86.2587F 2353:shortness of breath 2197:, a constituent of 2051:reactions such as: 2029:Alzheimer's disease 2024:autoimmune diseases 1823:autoimmune diseases 1460:bronchoconstriction 1417:chemotactic factors 1251:chaperone (protein) 1174:chemotactic factors 1075:-(S-glutathionyl)-7 7270:Enzyme superfamily 7203:Enzyme promiscuity 7127:Inositol oxygenase 7108:Firefly luciferase 7089:Chlorite dismutase 7061:other dioxygenase: 6639:3-Methoxytropolone 6563:N-Stearoyldopamine 5636:Inositol oxygenase 4447:10.1002/cncr.25945 4335:10.1093/cvr/cvt339 4257:ClinicalTrials.gov 4156:10.1111/bcpt.12114 3864:10.1038/nri.2015.4 3817:10.1007/bf02536528 3603:infection in mice" 3449:10.1002/cbin.10345 2538:10.1111/bcpt.12115 1937:respiratory system 1653:Transgenic studies 1544:omega-3 fatty acid 1311:omega-6 fatty acid 796:consisting of 673 663:housekeeping genes 613:) substrates into 7426: 7425: 7135: 7134: 6960: 6959: 6879: 6878: 6548:(St. John's Wort) 6474: 6459: 6458: 6455: 6454: 6169: 6168: 5921: 5864: 5863: 5659: 5658: 5421:(13): 8276–8280. 5182:(15): 6966–6970. 4953:(23): 9073–9077. 4861:978-0-306-47283-1 4821:(2 Pt 2): S11–5. 4685:10.1111/all.12260 4679:(10): 1219–1232. 4485:(12): 4111–4117. 4440:(16): 3788–3795. 4407:Kirste S (2009). 4290:(12): 1767–1775. 4052:10.1111/cea.12544 4046:(11): 1673–1680. 3918:10.1111/all.12821 3811:(12): 1184–1188. 3654:Trypanosoma cruzi 3337:and leukotriene B 3258:10.1111/bph.12665 3252:(15): 3551–3574. 3151:10.1159/000074640 3106:10.1172/JCI118480 2791:978-1-4899-0181-1 2751:10.1021/cr200246d 2745:(10): 5866–5898. 2393:chronic urticaria 2385:chronic urticaria 1767:cytotoxic T cells 1731:Toxoplasma gondii 1713:Trypanosoma cruzi 1268:-glycerol, and 1- 751:endothelial cells 569: 568: 565: 564: 468:metabolic pathway 372: 371: 368: 367: 344: 343: 307: 306: 288: 287: 264: 263: 245: 244: 221: 220: 204: 203: 174: 173: 157: 156: 133: 132: 116: 115: 7493: 7481:Lipid metabolism 7443: 7442: 7434: 7306:Hanes–Woolf plot 7249:Enzyme activator 7244:Enzyme inhibitor 7218:Enzyme catalysis 7162: 7155: 7148: 7139: 7138: 6987: 6980: 6973: 6964: 6963: 6914:Arachidonic acid 6859: 6855: 6828: 6824: 6796: 6792: 6769: 6765: 6707: 6703: 6665: 6661: 6627: 6623: 6587: 6583: 6488: 6484: 6478: 6477: 6468: 6434: 6430: 6371: 6367: 6198: 6194: 6185: 6184: 6181: 6177: 6095: 6091: 5952: 5948: 5939: 5938: 5935: 5931: 5925: 5924: 5915: 5891: 5884: 5877: 5868: 5867: 5719:Phospholipase A2 5697:lipid metabolism 5686: 5679: 5672: 5663: 5662: 5603:Bacterioferritin 5576:Carrier proteins 5569: 5562: 5555: 5546: 5545: 5504: 5487:(1–2): 149–156. 5475: 5465: 5456:(5): 1520–1528. 5440: 5430: 5405: 5376: 5355: 5345: 5328:(6): 1935–1946. 5312: 5295:(1–2): 171–174. 5283: 5254: 5244: 5219: 5209: 5199: 5166: 5156: 5131: 5121: 5111: 5078: 5068: 5043: 5033: 5023: 4990: 4980: 4970: 4937: 4927: 4902: 4885:(3): 1482–1490. 4873: 4838: 4800: 4799: 4789: 4765: 4759: 4758: 4747: 4741: 4740: 4729: 4723: 4722: 4711: 4705: 4704: 4667: 4661: 4660: 4650: 4618: 4612: 4611: 4601: 4569: 4560: 4559: 4549: 4517: 4511: 4510: 4474: 4468: 4467: 4449: 4425: 4419: 4418: 4404: 4398: 4397: 4387: 4363: 4357: 4356: 4346: 4314: 4308: 4307: 4279: 4273: 4272: 4265: 4259: 4247: 4241: 4240: 4238: 4237: 4218: 4212: 4211: 4175: 4169: 4168: 4158: 4134: 4121: 4120: 4110: 4078: 4072: 4071: 4035: 4029: 4028: 4018: 3986: 3980: 3979: 3961: 3937: 3931: 3930: 3920: 3895: 3886: 3885: 3875: 3843: 3837: 3836: 3800: 3794: 3793: 3783: 3751: 3745: 3744: 3734: 3702: 3696: 3695: 3685: 3675: 3647: 3641: 3640: 3630: 3613:(3): 1210–1216. 3601:Brucella abortus 3594: 3588: 3587: 3576: 3570: 3569: 3559: 3549: 3525: 3519: 3518: 3478: 3469: 3468: 3432: 3419: 3418: 3408: 3376: 3367: 3366: 3330: 3321: 3320: 3310: 3286: 3280: 3279: 3269: 3237: 3228: 3227: 3209: 3192:(5): 1039–1050. 3177: 3171: 3170: 3134: 3128: 3127: 3117: 3085: 3079: 3078: 3049: 3043: 3042: 3032: 3000: 2987: 2986: 2976: 2952: 2943: 2942: 2932: 2900: 2891: 2890: 2862: 2853: 2852: 2842: 2810: 2804: 2803: 2769: 2763: 2762: 2739:Chemical Reviews 2730: 2713: 2712: 2683: 2677: 2670: 2664: 2657: 2651: 2650: 2622: 2599: 2598: 2570: 2551: 2550: 2540: 2516: 2503: 2502: 2492: 2482: 2465:(8): 2587–2591. 2450: 2357:nasal congestion 1707:Brucella abortus 1692:. In a model of 1375:MRP1 transporter 1315:arachidonic acid 1305:Arachidonic acid 1301: 1278: 1196:phospholipase A2 1153:nuclear membrane 1141:protein kinase C 1137:protein kinase A 879:activity adds a 873:arachidonic acid 802:molecular weight 739:Langerhans cells 691:immune responses 594:iron-containing 574:, also known as 522: 521: 374: 373: 357: 356: 340: 335: 322: 317: 302: 292: 291: 283: 273: 272: 269:RefSeq (protein) 259: 249: 248: 240: 230: 229: 208: 207: 185: 184: 161: 160: 144: 143: 120: 119: 103: 102: 72: 71: 66: 40: 19: 18: 16:Class of enzymes 7501: 7500: 7496: 7495: 7494: 7492: 7491: 7490: 7451: 7450: 7449: 7437: 7429: 7427: 7422: 7334:Oxidoreductases 7320: 7296:Enzyme kinetics 7284: 7280:List of enzymes 7253: 7222: 7193:Catalytic triad 7171: 7166: 7136: 7131: 7112: 7093: 7005: 6994:Oxidoreductases 6991: 6961: 6956: 6931: 6927: 6875: 6857: 6854: 6844: 6826: 6822: 6812: 6794: 6790: 6780: 6767: 6763: 6753: 6705: 6701: 6691: 6663: 6653: 6625: 6615: 6585: 6486: 6467: 6451: 6447: 6432: 6429: 6419: 6400: 6392: 6384: 6369: 6366: 6356: 6227: 6219: 6211: 6196: 6193: 6179: 6165: 6141: 6133: 6093: 6090: 6080: 5996: 5978: 5970: 5950: 5947: 5933: 5914: 5906: 5895: 5865: 5860: 5844: 5798: 5735: 5726:Phospholipase C 5707: 5690: 5660: 5655: 5619: 5586: 5580:metalloproteins 5573: 5512: 5507: 5141:Eur. J. Biochem 4862: 4808: 4806:Further reading 4803: 4766: 4762: 4749: 4748: 4744: 4731: 4730: 4726: 4713: 4712: 4708: 4668: 4664: 4619: 4615: 4570: 4563: 4518: 4514: 4475: 4471: 4426: 4422: 4405: 4401: 4364: 4360: 4315: 4311: 4280: 4276: 4267: 4266: 4262: 4248: 4244: 4235: 4233: 4220: 4219: 4215: 4176: 4172: 4135: 4124: 4079: 4075: 4036: 4032: 3987: 3983: 3938: 3934: 3896: 3889: 3844: 3840: 3801: 3797: 3752: 3748: 3703: 3699: 3648: 3644: 3595: 3591: 3578: 3577: 3573: 3526: 3522: 3479: 3472: 3433: 3422: 3377: 3370: 3340: 3336: 3331: 3324: 3287: 3283: 3238: 3231: 3178: 3174: 3135: 3131: 3086: 3082: 3050: 3046: 3001: 2990: 2953: 2946: 2901: 2894: 2863: 2856: 2811: 2807: 2792: 2770: 2766: 2731: 2716: 2684: 2680: 2671: 2667: 2658: 2654: 2623: 2602: 2571: 2554: 2517: 2506: 2451: 2447: 2443: 2433: 2425:atherosclerosis 2416: 2414:Atherosclerosis 2377:wheal responses 2338: 2282: 2280:Allergic asthma 2269: 2257:corticosteroids 2156:clinical trials 2014:atherosclerosis 1988: 1982: 1929: 1857: 1845:dendritic cells 1813:atherosclerosis 1785:innate immunity 1781: 1776: 1740:innate immunity 1655: 1600: 1576:cytochrome P450 1540: 1501: 1307: 1293: 1256:diacylglycerols 1241: 1237: 1233: 1225: 1221: 1213: 1209: 1205: 1201: 1155:and, probably, 1117: 915:)-hydroperoxy-6 886: 790: 725:express ALOX5. 719:dendritic cells 679: 623: 361:View/Edit Human 338: 333: 320: 315: 312:Location (UCSC) 300: 281: 257: 238: 196: 51: 36: 17: 12: 11: 5: 7499: 7489: 7488: 7483: 7478: 7473: 7468: 7463: 7448: 7447: 7424: 7423: 7421: 7420: 7407: 7394: 7381: 7368: 7355: 7342: 7328: 7326: 7322: 7321: 7319: 7318: 7313: 7308: 7303: 7298: 7292: 7290: 7286: 7285: 7283: 7282: 7277: 7272: 7267: 7261: 7259: 7258:Classification 7255: 7254: 7252: 7251: 7246: 7241: 7236: 7230: 7228: 7224: 7223: 7221: 7220: 7215: 7210: 7205: 7200: 7195: 7190: 7185: 7179: 7177: 7173: 7172: 7165: 7164: 7157: 7150: 7142: 7133: 7132: 7130: 7129: 7123: 7121: 7114: 7113: 7111: 7110: 7104: 7102: 7095: 7094: 7092: 7091: 7086: 7081: 7076: 7071: 7066: 7057: 7056: 7051: 7042: 7037: 7028: 7016: 7014: 7007: 7006: 6998:monooxygenases 6990: 6989: 6982: 6975: 6967: 6958: 6957: 6955: 6954: 6947: 6940: 6936: 6933: 6932: 6930: 6929: 6925: 6921: 6916: 6911: 6909:Diacylglycerol 6906: 6901: 6896: 6887: 6885: 6881: 6880: 6877: 6876: 6874: 6873: 6868: 6862: 6860: 6852: 6846: 6845: 6843: 6842: 6837: 6831: 6829: 6820: 6814: 6813: 6811: 6810: 6805: 6799: 6797: 6788: 6782: 6781: 6779: 6778: 6772: 6770: 6761: 6755: 6754: 6752: 6751: 6746: 6741: 6736: 6731: 6726: 6721: 6716: 6710: 6708: 6699: 6693: 6692: 6690: 6689: 6684: 6679: 6674: 6668: 6666: 6655: 6654: 6652: 6651: 6646: 6641: 6636: 6630: 6628: 6617: 6616: 6614: 6613: 6608: 6603: 6598: 6593: 6576: 6575: 6570: 6565: 6560: 6555: 6550: 6542: 6537: 6532: 6527: 6522: 6517: 6512: 6507: 6502: 6497: 6491: 6489: 6475: 6461: 6460: 6457: 6456: 6453: 6452: 6450: 6449: 6445: 6437: 6435: 6427: 6421: 6420: 6418: 6417: 6412: 6403: 6402: 6398: 6394: 6390: 6386: 6382: 6374: 6372: 6364: 6358: 6357: 6355: 6354: 6349: 6344: 6339: 6334: 6329: 6324: 6319: 6314: 6309: 6304: 6299: 6294: 6289: 6284: 6279: 6274: 6269: 6264: 6259: 6254: 6249: 6244: 6239: 6230: 6229: 6225: 6221: 6217: 6213: 6209: 6201: 6199: 6191: 6182: 6171: 6170: 6167: 6166: 6164: 6163: 6158: 6153: 6144: 6143: 6139: 6135: 6131: 6130:20-Hydroxy-LTB 6127: 6122: 6117: 6112: 6107: 6098: 6096: 6088: 6082: 6081: 6079: 6078: 6073: 6068: 6063: 6058: 6053: 6048: 6043: 6038: 6033: 6028: 6023: 6018: 6013: 6008: 6003: 5998: 5994: 5993:20-Carboxy-LTB 5986: 5985: 5980: 5976: 5972: 5968: 5967:20-Hydroxy-LTB 5964: 5955: 5953: 5945: 5936: 5922: 5908: 5907: 5894: 5893: 5886: 5879: 5871: 5862: 5861: 5859: 5858: 5852: 5850: 5846: 5845: 5843: 5842: 5840:LTD4 hydrolase 5837: 5832: 5826: 5825: 5819: 5818: 5808: 5806: 5800: 5799: 5797: 5796: 5790: 5789: 5783: 5782: 5777: 5771: 5770: 5764: 5763: 5762: 5761: 5756: 5749:Cyclooxygenase 5745: 5743: 5737: 5736: 5734: 5733: 5728: 5722: 5721: 5715: 5713: 5709: 5708: 5689: 5688: 5681: 5674: 5666: 5657: 5656: 5654: 5653: 5648: 5643: 5638: 5633: 5627: 5625: 5621: 5620: 5618: 5617: 5612: 5607: 5606: 5605: 5594: 5592: 5588: 5587: 5572: 5571: 5564: 5557: 5549: 5543: 5542: 5523: 5511: 5510:External links 5508: 5506: 5505: 5476: 5441: 5406: 5388:(1): 108–114. 5377: 5367:(3): 145–150. 5361:J Lipid Mediat 5356: 5313: 5284: 5266:(5): 239–243. 5255: 5220: 5167: 5132: 5094:(2): 416–420. 5079: 5044: 4991: 4938: 4903: 4874: 4860: 4839: 4809: 4807: 4804: 4802: 4801: 4760: 4742: 4724: 4706: 4662: 4613: 4584:(3): 422–427. 4561: 4532:(4): 308–330. 4512: 4469: 4420: 4399: 4378:(9): 709–719. 4358: 4329:(3): 522–532. 4309: 4274: 4260: 4242: 4213: 4170: 4122: 4093:(3): 155–162. 4073: 4030: 3981: 3952:(1): 336–342. 3932: 3911:(4): 443–462. 3887: 3838: 3795: 3766:(2): 891–901. 3746: 3717:(2): a016311. 3697: 3642: 3589: 3571: 3520: 3470: 3420: 3391:(3): 200–215. 3368: 3338: 3334: 3322: 3301:(4): 347–355. 3281: 3229: 3172: 3145:(4): 285–294. 3129: 3100:(3): 806–813. 3080: 3061:(3): 228–236. 3044: 3015:(4): 651–665. 2988: 2944: 2915:(4): 340–355. 2892: 2854: 2805: 2790: 2764: 2714: 2678: 2665: 2652: 2633:(4): 331–339. 2600: 2581:(4): 410–422. 2552: 2504: 2444: 2442: 2439: 2432: 2429: 2415: 2412: 2369:rhinosinusitis 2337: 2334: 2281: 2278: 2268: 2267:Human genetics 2265: 2183:St John's wort 2108: 2107: 2104: 2103: 2102: 2097: 2092: 2091:conjunctivitis 2089: 2086: 2080: 2079: 2078: 2073: 2068: 2063: 2061:conjunctivitis 2058: 2034: 2033: 2032: 2031: 2026: 2021: 2016: 2011: 2003: 1984:Main article: 1981: 1978: 1973: 1972: 1966: 1961: 1959:conjunctivitis 1955: 1950: 1928: 1925: 1901: 1900: 1890: 1885: 1880: 1878:conjunctivitis 1875: 1856: 1853: 1826: 1825: 1820: 1815: 1810: 1801: 1800: 1780: 1777: 1775: 1772: 1763:T helper cells 1654: 1651: 1599: 1596: 1572:cyclooxygenase 1539: 1536: 1500: 1497: 1469:conjunctivitis 1306: 1303: 1292: 1289: 1239: 1235: 1231: 1223: 1219: 1211: 1207: 1206:set (i.e. cPLA 1203: 1199: 1116: 1113: 1047:or microsomal 1009:leukotriene B4 971:-HpETE to its 935:-HpETE). The 5 884: 869: 868: 849: 842: 835: 824:C2-like domain 817: 789: 786: 678: 675: 637:divided by 13 622: 619: 580:5-lipoxygenase 567: 566: 563: 562: 557: 551: 550: 545: 539: 538: 533: 527: 526: 518: 517: 508: 502: 501: 490: 483: 482: 477: 471: 470: 465: 459: 458: 453: 447: 446: 441: 435: 434: 429: 423: 422: 417: 411: 410: 406: 405: 402: 396: 395: 390: 384: 383: 379: 378: 370: 369: 366: 365: 363: 353: 352: 346: 345: 342: 341: 336: 331: 324: 323: 318: 313: 309: 308: 305: 304: 296: 295: 289: 286: 285: 277: 276: 270: 266: 265: 262: 261: 253: 252: 246: 243: 242: 234: 233: 227: 223: 222: 219: 218: 212: 211: 205: 202: 201: 189: 188: 182: 176: 175: 172: 171: 165: 164: 158: 155: 154: 148: 147: 141: 135: 134: 131: 130: 124: 123: 117: 114: 113: 107: 106: 100: 94: 93: 88: 83: 79: 78: 68: 67: 49: 45: 44: 43:5-lipoxygenase 41: 33: 32: 28: 27: 24: 23: 15: 9: 6: 4: 3: 2: 7498: 7487: 7484: 7482: 7479: 7477: 7474: 7472: 7469: 7467: 7464: 7462: 7459: 7458: 7456: 7446: 7441: 7436: 7435: 7432: 7418: 7414: 7413: 7408: 7405: 7401: 7400: 7395: 7392: 7388: 7387: 7382: 7379: 7375: 7374: 7369: 7366: 7362: 7361: 7356: 7353: 7349: 7348: 7343: 7340: 7336: 7335: 7330: 7329: 7327: 7323: 7317: 7314: 7312: 7309: 7307: 7304: 7302: 7299: 7297: 7294: 7293: 7291: 7287: 7281: 7278: 7276: 7275:Enzyme family 7273: 7271: 7268: 7266: 7263: 7262: 7260: 7256: 7250: 7247: 7245: 7242: 7240: 7239:Cooperativity 7237: 7235: 7232: 7231: 7229: 7225: 7219: 7216: 7214: 7211: 7209: 7206: 7204: 7201: 7199: 7198:Oxyanion hole 7196: 7194: 7191: 7189: 7186: 7184: 7181: 7180: 7178: 7174: 7170: 7163: 7158: 7156: 7151: 7149: 7144: 7143: 7140: 7128: 7125: 7124: 7122: 7119: 7115: 7109: 7106: 7105: 7103: 7100: 7096: 7090: 7087: 7085: 7082: 7080: 7077: 7075: 7072: 7070: 7067: 7065: 7062: 7059: 7058: 7055: 7052: 7050: 7046: 7043: 7041: 7038: 7036: 7032: 7029: 7027: 7024: 7022: 7018: 7017: 7015: 7012: 7008: 7003: 6999: 6995: 6988: 6983: 6981: 6976: 6974: 6969: 6968: 6965: 6953: 6952: 6948: 6946: 6945: 6941: 6938: 6937: 6934: 6928: 6924:Leukotriene A 6922: 6920: 6917: 6915: 6912: 6910: 6907: 6905: 6902: 6900: 6897: 6895: 6894:Linoleic acid 6892: 6889: 6888: 6886: 6882: 6872: 6869: 6867: 6864: 6863: 6861: 6856: 6847: 6841: 6838: 6836: 6833: 6832: 6830: 6825: 6815: 6809: 6806: 6804: 6801: 6800: 6798: 6793: 6783: 6777: 6774: 6773: 6771: 6766: 6756: 6750: 6747: 6745: 6742: 6740: 6737: 6735: 6732: 6730: 6727: 6725: 6722: 6720: 6717: 6715: 6712: 6711: 6709: 6704: 6694: 6688: 6685: 6683: 6680: 6678: 6675: 6673: 6670: 6669: 6667: 6662: 6656: 6650: 6647: 6645: 6642: 6640: 6637: 6635: 6632: 6631: 6629: 6624: 6618: 6612: 6609: 6607: 6604: 6602: 6599: 6597: 6594: 6592: 6589: 6584: 6578: 6577: 6574: 6571: 6569: 6566: 6564: 6561: 6559: 6556: 6554: 6551: 6549: 6547: 6543: 6541: 6538: 6536: 6533: 6531: 6528: 6526: 6523: 6521: 6518: 6516: 6513: 6511: 6508: 6506: 6503: 6501: 6498: 6496: 6493: 6492: 6490: 6485: 6479: 6476: 6472: 6466: 6462: 6448: 6444:Leukotriene E 6442: 6439: 6438: 6436: 6431: 6422: 6416: 6413: 6411: 6408: 6405: 6404: 6401: 6397:Leukotriene E 6395: 6393: 6389:Leukotriene D 6387: 6385: 6381:Leukotriene C 6379: 6376: 6375: 6373: 6368: 6359: 6353: 6350: 6348: 6345: 6343: 6340: 6338: 6335: 6333: 6330: 6328: 6325: 6323: 6320: 6318: 6315: 6313: 6310: 6308: 6305: 6303: 6300: 6298: 6295: 6293: 6290: 6288: 6285: 6283: 6280: 6278: 6275: 6273: 6270: 6268: 6265: 6263: 6260: 6258: 6255: 6253: 6250: 6248: 6245: 6243: 6240: 6238: 6235: 6232: 6231: 6228: 6224:Leukotriene E 6222: 6220: 6216:Leukotriene D 6214: 6212: 6208:Leukotriene C 6206: 6203: 6202: 6200: 6195: 6186: 6183: 6178: 6172: 6162: 6159: 6157: 6154: 6152: 6149: 6146: 6145: 6142: 6138:Leukotriene B 6136: 6134: 6128: 6126: 6123: 6121: 6118: 6116: 6113: 6111: 6108: 6106: 6103: 6100: 6099: 6097: 6092: 6083: 6077: 6074: 6072: 6069: 6067: 6064: 6062: 6059: 6057: 6054: 6052: 6049: 6047: 6044: 6042: 6039: 6037: 6034: 6032: 6029: 6027: 6024: 6022: 6019: 6017: 6014: 6012: 6009: 6007: 6004: 6002: 5999: 5997: 5991: 5988: 5987: 5984: 5981: 5979: 5975:Leukotriene B 5973: 5971: 5965: 5963: 5960: 5957: 5956: 5954: 5949: 5940: 5937: 5932: 5926: 5923: 5919: 5913: 5909: 5905: 5902: 5899: 5892: 5887: 5885: 5880: 5878: 5873: 5872: 5869: 5857: 5854: 5853: 5851: 5847: 5841: 5838: 5836: 5833: 5831: 5830:LTC4 synthase 5828: 5827: 5824: 5821: 5820: 5817: 5813: 5810: 5809: 5807: 5805: 5801: 5795: 5792: 5791: 5788: 5787:PGI2 synthase 5785: 5784: 5781: 5778: 5776: 5773: 5772: 5769: 5768:PGD2 synthase 5766: 5765: 5760: 5757: 5755: 5752: 5751: 5750: 5747: 5746: 5744: 5742: 5738: 5732: 5729: 5727: 5724: 5723: 5720: 5717: 5716: 5714: 5710: 5706: 5702: 5698: 5694: 5687: 5682: 5680: 5675: 5673: 5668: 5667: 5664: 5652: 5649: 5647: 5644: 5642: 5639: 5637: 5634: 5632: 5629: 5628: 5626: 5622: 5616: 5613: 5611: 5608: 5604: 5601: 5600: 5599: 5596: 5595: 5593: 5589: 5585: 5581: 5577: 5570: 5565: 5563: 5558: 5556: 5551: 5550: 5547: 5540: 5536: 5535: 5530: 5529: 5524: 5521: 5517: 5514: 5513: 5502: 5498: 5494: 5490: 5486: 5482: 5477: 5473: 5469: 5464: 5459: 5455: 5451: 5447: 5442: 5438: 5434: 5429: 5424: 5420: 5416: 5415:J. Biol. Chem 5412: 5407: 5403: 5399: 5395: 5391: 5387: 5383: 5382:Anal. Biochem 5378: 5374: 5370: 5366: 5362: 5357: 5353: 5349: 5344: 5339: 5335: 5331: 5327: 5323: 5319: 5314: 5310: 5306: 5302: 5298: 5294: 5290: 5285: 5281: 5277: 5273: 5269: 5265: 5261: 5256: 5252: 5248: 5243: 5238: 5234: 5230: 5229:J. Biol. Chem 5226: 5221: 5217: 5213: 5208: 5203: 5198: 5193: 5189: 5185: 5181: 5177: 5173: 5168: 5164: 5160: 5155: 5150: 5146: 5142: 5138: 5133: 5129: 5125: 5120: 5115: 5110: 5105: 5101: 5097: 5093: 5089: 5085: 5080: 5076: 5072: 5067: 5062: 5058: 5054: 5053:J. Biol. Chem 5050: 5045: 5041: 5037: 5032: 5027: 5022: 5017: 5013: 5009: 5005: 5001: 4997: 4992: 4988: 4984: 4979: 4974: 4969: 4964: 4960: 4956: 4952: 4948: 4944: 4939: 4935: 4931: 4926: 4921: 4917: 4913: 4912:J. Biol. Chem 4909: 4904: 4900: 4896: 4892: 4888: 4884: 4880: 4875: 4871: 4867: 4863: 4857: 4853: 4849: 4845: 4840: 4836: 4832: 4828: 4824: 4820: 4816: 4811: 4810: 4797: 4793: 4788: 4783: 4779: 4775: 4771: 4764: 4756: 4752: 4746: 4738: 4734: 4728: 4720: 4716: 4710: 4702: 4698: 4694: 4690: 4686: 4682: 4678: 4674: 4666: 4658: 4654: 4649: 4644: 4640: 4636: 4632: 4628: 4624: 4617: 4609: 4605: 4600: 4595: 4591: 4587: 4583: 4579: 4575: 4568: 4566: 4557: 4553: 4548: 4543: 4539: 4535: 4531: 4527: 4523: 4516: 4508: 4504: 4500: 4496: 4492: 4488: 4484: 4480: 4473: 4465: 4461: 4457: 4453: 4448: 4443: 4439: 4435: 4431: 4424: 4416: 4412: 4411: 4403: 4395: 4391: 4386: 4381: 4377: 4373: 4369: 4362: 4354: 4350: 4345: 4340: 4336: 4332: 4328: 4324: 4320: 4313: 4305: 4301: 4297: 4293: 4289: 4285: 4278: 4270: 4264: 4258: 4254: 4253: 4246: 4232:on 2019-08-19 4231: 4227: 4223: 4217: 4209: 4205: 4201: 4197: 4193: 4189: 4185: 4181: 4174: 4166: 4162: 4157: 4152: 4148: 4144: 4140: 4133: 4131: 4129: 4127: 4118: 4114: 4109: 4104: 4100: 4096: 4092: 4088: 4084: 4077: 4069: 4065: 4061: 4057: 4053: 4049: 4045: 4041: 4034: 4026: 4022: 4017: 4012: 4008: 4004: 4000: 3996: 3992: 3985: 3977: 3973: 3969: 3965: 3960: 3955: 3951: 3947: 3943: 3936: 3928: 3924: 3919: 3914: 3910: 3906: 3902: 3894: 3892: 3883: 3879: 3874: 3869: 3865: 3861: 3857: 3853: 3849: 3842: 3834: 3830: 3826: 3822: 3818: 3814: 3810: 3806: 3799: 3791: 3787: 3782: 3777: 3773: 3769: 3765: 3761: 3757: 3750: 3742: 3738: 3733: 3728: 3724: 3720: 3716: 3712: 3708: 3701: 3693: 3689: 3684: 3679: 3674: 3669: 3665: 3661: 3657: 3655: 3646: 3638: 3634: 3629: 3624: 3620: 3616: 3612: 3608: 3604: 3602: 3593: 3585: 3581: 3575: 3567: 3563: 3558: 3553: 3548: 3543: 3539: 3535: 3531: 3524: 3516: 3512: 3508: 3504: 3500: 3496: 3492: 3488: 3484: 3477: 3475: 3466: 3462: 3458: 3454: 3450: 3446: 3442: 3438: 3431: 3429: 3427: 3425: 3416: 3412: 3407: 3402: 3398: 3394: 3390: 3386: 3382: 3375: 3373: 3364: 3360: 3356: 3352: 3348: 3344: 3329: 3327: 3318: 3314: 3309: 3304: 3300: 3296: 3292: 3285: 3277: 3273: 3268: 3263: 3259: 3255: 3251: 3247: 3243: 3236: 3234: 3225: 3221: 3217: 3213: 3208: 3203: 3199: 3195: 3191: 3187: 3183: 3176: 3168: 3164: 3160: 3156: 3152: 3148: 3144: 3140: 3133: 3125: 3121: 3116: 3111: 3107: 3103: 3099: 3095: 3091: 3084: 3076: 3072: 3068: 3064: 3060: 3056: 3048: 3040: 3036: 3031: 3026: 3022: 3018: 3014: 3010: 3006: 2999: 2997: 2995: 2993: 2984: 2980: 2975: 2970: 2966: 2962: 2958: 2951: 2949: 2940: 2936: 2931: 2926: 2922: 2918: 2914: 2910: 2906: 2899: 2897: 2888: 2884: 2880: 2876: 2872: 2868: 2861: 2859: 2850: 2846: 2841: 2836: 2832: 2828: 2824: 2820: 2816: 2809: 2801: 2797: 2793: 2787: 2783: 2779: 2775: 2768: 2760: 2756: 2752: 2748: 2744: 2740: 2736: 2729: 2727: 2725: 2723: 2721: 2719: 2710: 2706: 2702: 2698: 2694: 2690: 2682: 2675: 2669: 2662: 2656: 2648: 2644: 2640: 2636: 2632: 2628: 2621: 2619: 2617: 2615: 2613: 2611: 2609: 2607: 2605: 2596: 2592: 2588: 2584: 2580: 2576: 2569: 2567: 2565: 2563: 2561: 2559: 2557: 2548: 2544: 2539: 2534: 2530: 2526: 2522: 2515: 2513: 2511: 2509: 2500: 2496: 2491: 2486: 2481: 2476: 2472: 2468: 2464: 2460: 2456: 2449: 2445: 2438: 2437: 2428: 2426: 2421: 2411: 2409: 2405: 2401: 2398: 2394: 2390: 2386: 2382: 2378: 2374: 2370: 2366: 2362: 2358: 2354: 2350: 2346: 2342: 2333: 2331: 2327: 2323: 2319: 2315: 2311: 2307: 2303: 2299: 2295: 2291: 2288:in the human 2287: 2284:The upstream 2277: 2275: 2264: 2262: 2258: 2254: 2248: 2246: 2242: 2237: 2233: 2229: 2225: 2221: 2216: 2214: 2212: 2206: 2204: 2200: 2196: 2192: 2188: 2184: 2180: 2179: 2174: 2172: 2168: 2164: 2160: 2157: 2153: 2149: 2145: 2144: 2139: 2137: 2133: 2130:for treating 2129: 2125: 2121: 2120:acne vulgaris 2115: 2113: 2105: 2101: 2098: 2096: 2093: 2090: 2087: 2084: 2083: 2081: 2077: 2074: 2072: 2069: 2067: 2064: 2062: 2059: 2057: 2053: 2052: 2050: 2046: 2043: 2042: 2041: 2039: 2030: 2027: 2025: 2022: 2020: 2017: 2015: 2012: 2010: 2007: 2006: 2004: 2001: 1997: 1993: 1992: 1991: 1987: 1977: 1970: 1967: 1965: 1962: 1960: 1957:non-allergic 1956: 1954: 1951: 1949: 1946: 1945: 1944: 1942: 1938: 1934: 1924: 1922: 1918: 1914: 1910: 1906: 1898: 1894: 1891: 1889: 1886: 1884: 1881: 1879: 1876: 1874: 1870: 1869: 1868: 1866: 1862: 1852: 1850: 1846: 1842: 1838: 1833: 1831: 1824: 1821: 1819: 1816: 1814: 1811: 1809: 1806: 1805: 1804: 1798: 1794: 1790: 1789: 1788: 1786: 1771: 1768: 1764: 1759: 1755: 1751: 1747: 1745: 1741: 1737: 1734:disease, and 1733: 1732: 1727: 1723: 1719: 1715: 1714: 1709: 1708: 1703: 1699: 1695: 1691: 1690: 1685: 1684: 1679: 1678: 1673: 1672:gene knockout 1670: 1666: 1664: 1660: 1650: 1648: 1644: 1641:The D series 1639: 1637: 1633: 1629: 1625: 1621: 1617: 1613: 1609: 1605: 1595: 1593: 1587: 1585: 1581: 1577: 1573: 1569: 1565: 1561: 1557: 1553: 1549: 1545: 1535: 1533: 1529: 1525: 1521: 1517: 1513: 1509: 1505: 1496: 1494: 1490: 1486: 1480: 1478: 1474: 1470: 1466: 1461: 1457: 1453: 1449: 1445: 1441: 1439: 1435: 1431: 1426: 1422: 1418: 1415:as leukocyte 1414: 1410: 1406: 1402: 1398: 1396: 1392: 1388: 1384: 1380: 1376: 1372: 1371:LTC4 synthase 1368: 1364: 1360: 1356: 1352: 1348: 1344: 1340: 1336: 1332: 1328: 1324: 1320: 1316: 1312: 1302: 1300: 1288: 1286: 1282: 1276: 1271: 1267: 1266: 1261: 1257: 1252: 1248: 1243: 1229: 1217: 1214:enzymes (see 1197: 1193: 1192:phospholipids 1189: 1188: 1183: 1178: 1175: 1170: 1166: 1162: 1158: 1154: 1150: 1146: 1142: 1138: 1134: 1130: 1126: 1122: 1112: 1110: 1104: 1102: 1098: 1094: 1090: 1086: 1082: 1078: 1074: 1070: 1066: 1062: 1058: 1054: 1050: 1046: 1045:LTC4 synthase 1042: 1038: 1034: 1030: 1026: 1022: 1018: 1014: 1011:(LTB4, i.e. 5 1010: 1006: 1002: 998: 994: 990: 986: 982: 978: 974: 970: 966: 962: 958: 954: 950: 946: 942: 938: 934: 930: 926: 922: 918: 914: 910: 906: 902: 898: 894: 890: 882: 878: 874: 866: 862: 858: 854: 850: 847: 843: 840: 836: 833: 829: 825: 822: 818: 815: 811: 810: 809: 807: 803: 799: 795: 785: 783: 779: 774: 772: 768: 762: 760: 756: 752: 748: 747:smooth muscle 744: 740: 736: 732: 728: 724: 723:B-lymphocytes 720: 716: 712: 708: 704: 700: 696: 692: 688: 684: 674: 672: 668: 664: 660: 656: 652: 648: 647:gene promoter 644: 640: 636: 632: 628: 618: 616: 612: 608: 604: 601: 597: 593: 589: 585: 581: 577: 573: 561: 558: 556: 552: 549: 546: 544: 540: 537: 534: 532: 528: 523: 519: 516: 512: 509: 507: 506:Gene Ontology 503: 500: 497: 494: 491: 488: 484: 481: 478: 476: 472: 469: 466: 464: 460: 457: 454: 452: 448: 445: 444:NiceZyme view 442: 440: 436: 433: 430: 428: 424: 421: 418: 416: 412: 407: 403: 401: 397: 394: 391: 389: 385: 380: 375: 362: 358: 354: 351: 347: 337: 332: 329: 325: 319: 314: 310: 303: 297: 293: 290: 284: 278: 274: 271: 267: 260: 254: 250: 247: 241: 235: 231: 228: 226:RefSeq (mRNA) 224: 217: 213: 209: 206: 200: 199: 195: 190: 186: 183: 181: 177: 170: 166: 162: 159: 153: 149: 145: 142: 140: 136: 129: 125: 121: 118: 112: 108: 104: 101: 99: 95: 92: 89: 87: 84: 80: 77: 73: 69: 65: 61: 57: 54: 46: 39: 34: 29: 25: 20: 7412:Translocases 7409: 7396: 7383: 7370: 7357: 7347:Transferases 7344: 7331: 7188:Binding site 7060: 7025: 7021:lipoxygenase 7019: 6949: 6942: 6890: 6734:JNJ-26993135 6729:Fosinoprilat 6579: 6545: 6515:Caffeic acid 6481: 6440: 6407:Antagonists: 6406: 6377: 6234:Antagonists: 6233: 6204: 6148:Antagonists: 6147: 6101: 5990:Antagonists: 5989: 5958: 5815: 5804:Leukotrienes 5794:TXA synthase 5775:PGE synthase 5646:Lipoxygenase 5533: 5527: 5484: 5480: 5453: 5449: 5418: 5414: 5385: 5381: 5364: 5360: 5325: 5321: 5292: 5288: 5263: 5259: 5232: 5228: 5179: 5175: 5147:(1): 37–46. 5144: 5140: 5091: 5087: 5056: 5052: 5006:(1): 26–30. 5003: 4999: 4950: 4946: 4915: 4911: 4882: 4878: 4843: 4818: 4814: 4780:(1): 29–37. 4777: 4773: 4763: 4754: 4745: 4736: 4727: 4718: 4709: 4676: 4672: 4665: 4630: 4626: 4616: 4581: 4577: 4529: 4525: 4515: 4482: 4478: 4472: 4437: 4433: 4423: 4414: 4409: 4402: 4375: 4371: 4361: 4326: 4322: 4312: 4287: 4283: 4277: 4269:"PF-4191834" 4263: 4250: 4245: 4234:. 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Exp. 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