Arachidonate-5-lipoxygenase
| Arachidonate-5-lipoxygenase | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 673 amino acids | |
| Secondary to quaternary structure | peripheral membrane protein | |
| Cofactor | Fe, 2 approx | |
| Identifier | ||
| Gene name | ALOX5 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 1.13.11.34 , dioxygenase | |
| Response type | Addition of two oxygen atoms | |
| Substrate | Arachidonate + O 2 | |
| Products | Leukotriene A4 + H 2 O | |
| Occurrence | ||
| Homology family | Lipoxygenases type 2 | |
| Parent taxon | Euteleostomi | |
Arachidonate-5-lipoxygenase (5-LO) is the enzyme that oxidizes arachidonic acid in two steps to the eicosanoid leukotriene A4 . With this reaction, the biosynthesis of the more stable leukotrienes B4 to E4, which act as hormones in mammals , begins . In plants, instead of arachidonic acid, linoleic acid is oxidized. Similarly, 5-LO occurs in mammals and plants. In humans it is found in all types of tissue .
The enzyme belongs to the group of lipoxygenases .
The mammalian enzyme requires the FLAP protein ( arachidonate-5-lipoxygenase-activating protein ) for function. Variants of FLAP and of 5-LO are responsible for an increased risk of stroke and myocardial infarction or atherosclerosis in humans . The expression of 5-LO is upregulated in several tumor cell lines and possibly associated there with the formation of new blood vessels. For these reasons, 5-LO is a target for the treatment of cardiovascular disease and cancer.
Catalyzed reactions
+ O 2 →
→ 
+ H 2 O
Arachidonic acid is oxidized to the peroxide 5-HpETE, which decomposes to the epoxide leukotriene A4.
Individual evidence
- ↑ UniProt P09917
- ↑ UniProt P20292
- ↑ Allayee H, Baylin A, Hartiala J, et al : Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction . In: Am. J. Clin. Nutr. . 88, No. 4, October 2008, pp. 934-40. PMID 18842779 .
- ↑ Barresi V, Vitarelli E, Tuccari G, Barresi G: Correlative study of microvessel density and 5-lipoxygenase expression in human sporadic colorectal cancer . In: Arch. Pathol. Lab. Med. . 132, No. 11, November 2008, pp. 1807-12. PMID 18976020 .
- ↑ Melstrom LG, Bentrem DJ, Salabat MR, et al : Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model . In: Clin. Cancer Res . 14, No. 20, October 2008, pp. 6525-30. doi : 10.1158 / 1078-0432.CCR-07-4631 . PMID 18927292 .
- ↑ Sveinbjörnsson B, Rasmuson A, Baryawno N, et al : Expression of enzymes and receptors of the leukotriene pathway in human neuroblastoma promotes tumor survival and provides a target for therapy . In: FASEB J . . 22, No. 10, October 2008, pp. 3525-36. doi : 10.1096 / fj.07-103457 . PMID 18591367 .
Web links
- Jassal / D'Eustachio / reactome.org: Oxidation of arachidonic acid to 5-HpETE
- Jassal / D'Eustachio / reactome.org: Dehydration of 5-HpETE to leukotriene A4
- Georg Löffler: Biochemistry and Pathobiochemistry. Springer Berlin Heidelberg, 2007, ISBN 978-3-540-32681-6 , p. 423 ( limited preview in Google book search).