Arachidonat-5-Lipoxygenase

Arachidonat-5-Lipoxygenase

Vorhandene Strukturdaten: PDB 2abv

Eigenschaften des menschlichen Proteins
Masse/Länge Primärstruktur 673 Aminosäuren
Sekundär- bis Quartärstruktur peripheres Membranprotein
Kofaktor Fe, 2 Ca
Bezeichner
Gen-Name ALOX5
Externe IDs
Enzymklassifikation
EC, Kategorie 1.13.11.34, Dioxygenase
Reaktionsart Addition zweier Sauerstoffatome
Substrat Arachidonat + O2
Produkte Leukotrien A4 + H2O
Vorkommen
Homologie-Familie Lipoxygenasen Typ 2
Übergeordnetes Taxon Euteleostomi

Arachidonat-5-Lipoxygenase (5-LO) ist das Enzym, das Arachidonsäure in zwei Schritten zu dem Eicosanoid Leukotrien A4 oxidiert. Mit dieser Reaktion beginnt die Biosynthese der stabileren Leukotriene B4 bis E4, die als Hormone in Säugetieren agieren. In Pflanzen wird anstelle von Arachidonsäure die Linolsäure oxidiert. Entsprechend kommt 5-LO in Säugetieren und Pflanzen vor. Beim Menschen ist sie in allen Gewebetypen zu finden.[1]

Das Enzym gehört zu den Lipoxygenasen.

Das Säugetierenzym benötigt das FLAP-Protein (Arachidonat-5-Lipoxygenase-aktivierendes Protein) für die Funktion. Varianten von FLAP und von 5-LO sind beim Menschen für erhöhtes Risiko für Schlaganfall und Herzinfarkt bzw. Atherosklerose verantwortlich. Die Expression von 5-LO ist in mehreren Tumorzelllinien hochreguliert und möglicherweise dort mit der Neubildung von Blutgefäßen assoziiert. Aus diesen Gründen ist 5-LO ein Target für die Behandlung von Herz-Kreislauferkrankungen und Krebs.[2][3][4][5][6]

Katalysierte Reaktionen

Arachidonat + O2 →
5-HpETE → LTA4 + H2O

Arachidonsäure wird zum Peroxid 5-HpETE oxidiert, das sich zum Epoxid Leukotrien A4 zersetzt.

Wikibooks: Biochemie und Pathobiochemie: Arachidonsäure-Stoffwechsel – Lern- und Lehrmaterialien

Einzelnachweise

  1. ↑ UniProt P09917
  2. ↑ UniProt P20292
  3. ↑ Allayee H, Baylin A, Hartiala J, et al: Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction. In: Am. J. Clin. Nutr. 88. Jahrgang, Nr. 4, Oktober 2008, S. 934–40, PMID 18842779.
  4. ↑ 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. Jahrgang, Nr. 11, November 2008, S. 1807–12, PMID 18976020.
  5. ↑ 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. Jahrgang, Nr. 20, Oktober 2008, S. 6525–30, doi:10.1158/1078-0432.CCR-07-4631, PMID 18927292.
  6. ↑ 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. Jahrgang, Nr. 10, Oktober 2008, S. 3525–36, doi:10.1096/fj.07-103457, PMID 18591367.

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