Evidence for a 5(6)‐epoxytetraene intermediate in the biosynthesis of lipoxins in human leukocytes

FEBS Letters

Webber, Stephen E.²  Samuelsson, Bengt¹  Nicolaou, K.C.²  Puustinen, Tapio¹  Haeggström, Jesper¹  Serhan, Charles N.¹ 

[1] >Department of Physiological Chemistry, Karolinska Institutet, S-104 01 Stockholm, Sweden;Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

关键词: Arachidonic acid;    Conjugated tetraene;    Lipoxygenase interaction product;    (Human);    Leukocyte;    Epoxide;    LX;    lipoxin;    15-HPETE;    15(5)-hydroperoxy-5;    8;    11-cis-13-trans-eicosatetraenoic acid;    15-HETE;    15(S)-hydroxy-5;    8;    11-cis-13-trans-eicosatetraenoic acid;    GC/MS;    gas chromatography-mass spectrometry;    UV;    ultraviolet;    RP-HPLC;    reversed-phase high-performance liquid chromatography;    Me3Si;    trimethylsilyl;   

DOI  :  10.1016/0014-5793(86)80025-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The existence of a 15(S)-hydroxy-5,6-oxido-7,9,13-trans 11-cis-eicosatetraenoic acid intermediate in the biosyntheses of lipoxins A and B has recently been proposed. In the present study, human leukocytes were exposed to 15-HETE and the divalent cation ionophore A23187 and alcohol trapping studies were performed. The products containing alkyltetraenes were isolated and characterized. HPLC analysis, UV spectroscopy and GC/MS of the products showed that 5,15-dihydroxy-14-O-alkyleicosatetraenoic acids were formed, indicating that 5(6)-epoxytetraenes (precursor of the trapping product) were formed in human leukocytes. To gain further evidence for the role of 5(6)-epoxytetraene intermediate in the biosynthesis of lipoxins, (15)-hydroxy-5,6-oxido- 7,9,13-trans-11-cis-eicosatetraenoic acid was prepared by total chemical synthesis. When added to purified human liver cytosolic epoxide hydrolase, the epoxide was rapidly and quantitatively converted into LXA. The results provide further evidence for the role of a 5(6)epoxytetraene intermediate in the biosynthesis of lipoxins.

【 授权许可】

Unknown