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Arachidonate 5-lipoxygenase also known as 5-lipoxygenase or 5-LO is an enzyme that in humans is encoded by the ALOX5 gene.^[1] Arachidonate 5-lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms EFAs into leukotrienes and is a current target for pharmaceutical intervention in a number of diseases.

Substrates and products

EFA substrates and leukotriene products of 5-LO include:

Arachidonic acid (AA) yields the 4-series leukotrienes (LTB4, LTC4, LTD4, LTE4 — generally proinflammatory)
Eicosapentaenoic acid (EPA) yields the 5-series (LTB5, LTC5, LTD5, LTE5 — antiinflammatory)
Gamma-linolenic acid (GLA via the DGLA intermediary) yields no leukotrienes, but inhibits the conversion of AA.

Function

5-LO catalyzes oxidation of AA at the 5-position to yield 5-hydroperoxyeicosatetraenoic acid (5-HPETE). 5-LO then converts 5-HPETE to leukotriene A4.^[2]

Eicosanoid synthesis.

Two other lipoxygenases, 12-LO and 15-LO, act at the 12- and 15-positions, yielding 12- and 15-HPETE. These pathways lead to the leukotriene 12-hydroxyeicosatetraenoic acid (12-HETE) and to the lipoxins, respectively.^[3]

Clinical significance

5-LO is a target for pharmaceutical intervention in CAD.^[4] Some people with variant alleles for 5-LO are at elevated risk for CAD.^[5] 5-LO is expressed in brain cells and may participate in neuropathologic processes.^[6]

Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined.^[7]

5-LO inhibitors

As leukotrienes are important causes of pathological symptoms in asthma, 5-LO inhibitors were developed as asthma treatments. The only 5-LO inhibitor currently licensed for human use in asthma is Zileuton. Minocycline, although primarily a tetracycline antibiotic, is also a 5-LO inhibitor.^[8] It may therefore be used as a DMARD-medication in mild rheumatoid arthritis and other rheumatic conditions.^[9]

Activation

5-LO is activated by 5-lipoxygenase activating protein (FLAP).

Interactions

Arachidonate 5-lipoxygenase has been shown to interact with Grb2^[10]^[11] and COTL1.^[12]

References

^ Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B (April 1989). "Characterization of the human 5-lipoxygenase gene". Proc. Natl. Acad. Sci. U.S.A. 86 (8): 2587–91. doi:10.1073/pnas.86.8.2587. PMC 286962. PMID 2565035. //www.ncbi.nlm.nih.gov/pmc/articles/PMC286962/.
^ Reaction R01595 and R03058 at KEGG Pathway Database.
^ Dorlands Medical Dictionary, entries at arachidonate 5-lipoxygenase and following. Retrieved on 2006-02-07.
^ "5-Lipoxygenase, A New Therapeutic And Diagnostic Target For Heart Disease Management". UCLA Case No. 2001-429 PCT Publication Number: WO 03/035670 A2. Archived from the original on 2006-08-30. http://web.archive.org/web/20060830025600/http://www.research.ucla.edu/tech/ucla01-429.htm. Retrieved 2007-11-18.
^ Dwyer JH, Allayee H, Dwyer KM, et al. (2004). "Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis". N. Engl. J. Med. 350 (1): 29–37. doi:10.1056/NEJMoa025079. PMID 14702425.
^ Zhang L, Zhang WP, Hu H, et al. (2006). "Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytoma". Neuropathology : official journal of the Japanese Society of Neuropathology 26 (2): 99–106. doi:10.1111/j.1440-1789.2006.00658.x. PMID 16708542.
^ "Entrez Gene: ALOX5 arachidonate 5-lipoxygenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=240.
^ can be used as DMARDS. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z (2004). "Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation". Neuroreport 15 (14): 2181–4. doi:10.1097/00001756-200410050-00007. PMID 15371729.
^ arthritis.about.com: Minocin - Minocycline - Dosage - Side Effects - Drug Interactions
^ VanderNoot, V A; Fitzpatrick F A (September 1995). "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2". Anal. Biochem. (UNITED STATES) 230 (1): 108–14. doi:10.1006/abio.1995.1444. ISSN 0003-2697. PMID 8585605.
^ Lepley, R A; Fitzpatrick F A (September 1994). "5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins". J. Biol. Chem. (UNITED STATES) 269 (39): 24163–8. ISSN 0021-9258. PMID 7929073.
^ Provost, P; Doucet J, Hammarberg T, Gerisch G, Samuelsson B, Radmark O (May 2001). "5-Lipoxygenase interacts with coactosin-like protein". J. Biol. Chem. (United States) 276 (19): 16520–7. doi:10.1074/jbc.M011205200. ISSN 0021-9258. PMID 11297527.

External links

Arachidonate+5-Lipoxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 喘息の治療において5-リポキシゲナーゼ経路に影響する薬剤 agents affecting the 5 lipoxygenase pathway in the treatment of asthma
2. アスピリンによる呼吸器疾患の増悪 aspirin exacerbated respiratory disease
3. 肥満細胞由来のメディエーター mast cell derived mediators
4. 12歳未満の小児における慢性喘息：持続性喘息の治療およびコントロール薬 asthma in children younger than 12 years treatment of persistent asthma with controller medications
5. 思春期および成人における重症喘息の治療 treatment of severe asthma in adolescents and adults

English Journal

Activated LTB4 pathway in muscle tissue of patients with polymyositis or dermatomyositis.

Loell I, Alemo Munters L, Pandya J, Zong M, Alexanderson H, Fasth AE, Ståhl Hallengren C, Rådmark O, Lundberg IE, Jakobsson PJ, Korotkova M.SourceCorrespondence to Dr Ingela Loell, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm SE-171 76, Sweden; Ingela.Loell@ki.se.
Annals of the rheumatic diseases.Ann Rheum Dis.2013 Feb;72(2):293-9. doi: 10.1136/annrheumdis-2012-201294. Epub 2012 Jun 26.
OBJECTIVE: To investigate the involvement of the leukotriene B4 (LTB4) pathway in polymyositis (PM) and dermatomyositis (DM) and the effect of immunosuppressive treatment on the LTB4 pathway.METHODS: 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP) and LTB4 receptor-1 (BLT1) expression was anal
PMID 22736094

Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: Signaling cascade and drug-DNA interaction.

Bishayee K, Chakraborty D, Ghosh S, Boujedaini N, Khuda-Bukhsh AR.SourceCytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
European journal of pharmacology.Eur J Pharmacol.2013 Jan 5;698(1-3):110-21. doi: 10.1016/j.ejphar.2012.10.041. Epub 2012 Nov 6.
When the prostate cancer cells become unresponsive to androgen therapy, resistance to chemotherapy becomes imminent, resulting in high mortality. To combat this situation, lycopodine, a pharmacologically important bioactive component derived from Lycopodium clavatum spores, was tested against hormon
PMID 23142370

Japanese Journal

The Expression of Groups IIE and V Phospholipase A2 is Associated with an Increased Expression of Osteogenic Molecules in Human Calcified Aortic Valves

Suzuki Koji,Takahashi Soichiro,Watanabe Kazuhiro,Fujioka Daisuke,Nakamura Takamitsu,Obata Jun-ei,Kawabata Ken-ichi,Katoh Ryohei,Matsumoto Masahiko,Kugiyama Kiyotaka
Journal of Atherosclerosis and Thrombosis, 2014
… In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. …
NAID 130004677974

Expression Analysis of Leukotriene-Inflammatory Gene Interaction Network in Patients with Coronary Artery Disease

Nair Jiny,Shanker Jayashree,Jambunathan Srikarthika,Arvind Prathima,Kakkar Vijay V
Journal of Atherosclerosis and Thrombosis 21(4), 329-345, 2014
… We aimed to construct a network of interactions between leukotrienes and inflammatory biomarkers and evaluate the expression of key members of the leukotriene pathway and leukotriene-induced inflammatory molecules in patients with coronary artery disease(CAD) and healthy controls.Methods: Leukotrienes and their regulatory inflammatory molecules reported in the literature were used to construct a biological network employing Gene spring GX v12.5. …
NAID 130004444722

Potential New Therapeutic Targets for Pathological Pruritus

Kuraishi Yasushi
Biological and Pharmaceutical Bulletin 36(8), 1228-1234, 2013
… Newly identified potential targets for pathological pruritus include receptors (histamine H4 receptor, leukotriene B4 receptors, interleukin-31 receptor A, bombesin BB2 receptor, toll-like receptor 3, α-adrenoceptor, and opioid μ- and κ-receptors), channels (transient receptor potential (TRP) V3 and TRPA1 channels), and enzymes (histidine decarboxylase, sphingomyelin glucosylceramide deacylase, 5-lipoxygenase, leukotriene A4 hydrolase, and autotaxin). …
NAID 130003361502

Related Pictures

★リンクテーブル★

リンク元	「アラキドン酸」「5-HPETE」
拡張検索	「arachidonate 15-lipoxygenase」「arachidonate 5-lipoxygenase」「15-lipoxygenase」
関連記事	「lipoxygenase」

「アラキドン酸」

arachidonate 5-lipoxygenase
Identifiers
EC number	1.13.11.34
CAS number	80619-02-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

Arachidonate 5-lipoxygenase
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3O8Y, 3V92, 3V98, 3V99
Identifiers
Symbols	ALOX5; 5-LO; 5-LOX; 5LPG; LOG5
External IDs	OMIM: 152390 MGI: 87999 HomoloGene: 561 ChEMBL: 215 GeneCards: ALOX5 Gene
EC number	1.13.11.34
Gene Ontology
Molecular function	• arachidonate 5-lipoxygenase activity; • iron ion binding; • protein binding; • lipoxygenase activity;
Cellular component	• nuclear envelope; • nuclear envelope lumen; • cytosol; • nuclear matrix; • dendrite; • nuclear membrane; • sarcolemma;
Biological process	• acute inflammatory response; • leukotriene production involved in inflammatory response; • leukotriene metabolic process; • response to nutrient; • sensory perception of pain; • arachidonic acid metabolic process; • leukotriene biosynthetic process; • lipoxygenase pathway; • positive regulation of vasoconstriction; • response to hyperoxia;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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