Dioxygenation of N‐linoleoyl amides by soybean lipoxygenase‐1

FEBS Letters

Nieuwenhuizen, Willem F¹  Vliegenthart, Johannes F.G¹  van der Stelt, Marcelis¹  Veldink, Gerrit A¹ 

[1] Bijvoet Center for Biomolecular Research, Department of Bio-Organic Chemistry, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, The Netherlands

关键词: Cannabinoid;    Fatty acid amide;    N-Linoleoyl amide;    N-Linoleoyl ethanolamide;    Lipoxygenase;    CB1/2;    cannabinoid binding receptor 1 or 2;    CD;    circular dichroism;    CP-HPLC;    chiral-phase high-performance liquid chromatography;    2D-NMR;    2-dimensional nuclear magnetic resonance;    FPLC;    fast protein liquid chromatography;    FT-IR;    Fourier transform infrared (spectrometry);    GC-MS;    gas chromatography-mass spectrometry;    1H-NMR;    1H-nuclear magnetic resonance;    13-HOD;    13-hydroxy-9Z;    11E-octadeca-9;    11-dienoic acid;    13-HODNH2;    13-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl-N-amide;    13-HODNHEtOH;    13-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl-N-ethanolamide;    13-HODNHMe;    13-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl-N-methylamide;    13-HODN(Me)2;    13-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl-N;    N-dimethylamide;    LOX-1;    lipoxygenase-1;    OD;    9Z;    12Z-octadecadienoicacid (linoleic acid);    ODNH2;    9Z;    12Z-octadeca-9;    12-dienoyl-N-amide;    ODNHEtOH;    9Z;    12Z-octadeca-9;    12-dienoyl-N-ethanolamide;    ODNHMe;    9Z;    12Z-octadeca-9;    12-dienoyl-N-methylamide;    ODN(Me)2;    9Z;    12Z-octadeca-9;    12-dienoyl-N;    N-dimethylamide;    RP-HPLC;    reversed-phase high-performance liquid chromatography;    UV;    ultraviolet (spectrophotometry);    THC;    tetrahydrocannabinol;    TOCSY;    total correlation spectroscopy;   

DOI  :  10.1016/S0014-5793(97)00718-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Anandamide, a novel neurotransmitter, has been reported to be dioxygenated by brain lipoxygenase [1, 11]. Anandamides constitute a new class of neuroregulatory fatty acid amides. However, little is known about the enzymatic dioxygenation of these lipids. Therefore, we have tested several members of the neuroactive fatty acid amide class containing a 1Z,4Z-pentadiene system whether they could be dioxygenated by soybean lipoxygenase-1, which is a model enzyme for mammalian lipoxygenases. In this study it was found that lipoxygenase-1 converts N-linoleoylethanolamide (ODNHEtOH), N-linoleoylamide (ODNH₂), N-linoleoylmethylamide (ODNHMe) and N,N-linoleoyldimethylamide (ODN(Me)₂ into 13-(S)-hydroperoxy-9Z,11E-octadeca-9,11-dienoyl amides derivatives. The apparent K _m values for ODNHEtOH (23.6±3.7 μM), ODNH₂ (8.60±0.65 μM) and linoleic acid (OD: 8.85±0.74 μM) are not significantly different. The k _cat for ODNH₂ (32.4±1.2 s⁻¹) is twice as small as compared to the turnover numbers of the other substrates, viz. ODNHEtOH (61.6±5.0 s⁻¹) and OD (54.4±2.0 s⁻¹⁾. The results suggest that N-linoleoyl ethanolamide and N-linoleoyl amide can be readily converted by lipoxygenases in vivo.

【 授权许可】

Unknown