Dioxygenation of <i>N</i>‐linoleoyl amides by soybean lipoxygenase‐1

Stelt, Marcelis van der; Nieuwenhuizen, W.; Veldink, Gerrit A.; Vliegenthart, Johannes F.G.

doi:10.1016/s0014-5793(97)00718-7

Cited by 26 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HAEAs were isolated with SPE (Bakerbond, 500 mg), analyzed, and purified by reversed phase and chiral phase high-performance liquid chromatography (HPLC) as reported. 44,45,48 12 (q, 1H), 3.72 (t, 2H) 3.42 (q, 2H), 2.97 (m, 2H), 2,82 (m, 2H), 2.22 (t, J ) 7.5 Hz, 2H), 2.11 (m, 2H), 1.72 (q, J ) 40, February 18, 1992) and were approved by the Animal Care Committee (University of Rome "Tor Vergata"). Rat forebrain and spleen membrane preparations were obtained using the method of Devane et al 49 and were stored at a concentration of 1 mg mL -1 protein in 50 mM Tris‚HCl, 2 mM Tris‚EDTA, 3 mM MgCl2 buffer, pH 7.4, at -80°C for no longer than 1 week.…”

Section: Methodsmentioning

confidence: 99%

Oxygenated Metabolites of Anandamide and 2-Arachidonoylglycerol: Conformational Analysis and Interaction with Cannabinoid Receptors, Membrane Transporter, and Fatty Acid Amide Hydrolase

et al. 2002

View full text Add to dashboard Cite

This study was aimed at finding structural requirements for the interaction of the acyl chain of endocannabinoids with cannabinoid receptors, membrane transporter protein, and fatty acid amide hydrolase (FAAH). To this end, the flexibility of the acyl chain was restricted by introduction of an 1-hydroxy-2Z,4E-pentadiene system in anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) at various positions using different lipoxygenases. This brought about selectivity and attenuated the binding potency of AEA and 2-AG. Although the displacement constants were modest, 15(S)-hydroxy-eicosa-5Z,8Z,11Z,-13E-tetraenoyl-N-(2-hydroxyethyl)amine was found to bind selectively to the CB 1 receptor, whereas its 1-arachidonoyl-sn-glycerol analogue and 13(S)-hydroxy-octadeca-9Z,11E-dienoyl-N-(2-hydroxyethyl)amine could selectively bind to the CB 2 receptor. 11(S)-Hydroxy-eicosa-5Z,8Z,12E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine did not bind to either receptor, whereas 12(S)-hydroxy-eicosa-5Z,8Z,10E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine did bind to both CB receptors with an affinity similar to that of AEA. All oxygenated anandamide derivatives were good inhibitors of FAAH (low micromolar K i ) but were ineffective on the AEA transporter. 2-AG rapidly isomerizes into 1(3)-arachidonoyl-sn-glycerol. Both 1-and 3-arachidonoyl-snglycerol did not bind to either CB receptor and did not interfere with AEA transport. Thus, after it is isomerized, 2-AG is inactivated, thereby decreasing effective concentrations of 2-AG. Analysis of 1 H NMR spectra revealed that chloroform did not induce notably different conformations in the acyl chain of 15(S)-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid as compared with water. Molecular dynamics (MD) simulations of AEA and its analogues in the presence of explicit water molecules revealed that a tightly folded conformation of the acyl chain is not the only requirement for CB 1 binding. Structural details of the C 2 -C 15 loop, such as an sp 2 carbon at position 11, are necessary for receptor binding. The MD simulations may suggest that the average orientations of the pentyl tail of AEA and 12(S)-hydroxy-eicosa-5Z,8Z,-10E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine are different from that of the low-affinity, inactive ligands.

show abstract

Section: Methodsmentioning

confidence: 99%

Oxygenated Metabolites of Anandamide and 2-Arachidonoylglycerol: Conformational Analysis and Interaction with Cannabinoid Receptors, Membrane Transporter, and Fatty Acid Amide Hydrolase

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that NAE 18:2 and NAE 18:3 could be converted into hydroperoxy NAE by purified soybean (Glycine max) lipoxygenase-1 (LOX; Van der Stelt et al, 1997, 2000. The hydroperoxides of NAE 18:2 and NAE 18:3 could subsequently be converted by alfalfa (Medicago sativa) hydroperoxide (HPO) lyase and flax (Linum usitatissimum) seed allene oxide synthase (AOS) into novel oxylipins (Van der Stelt et al, 2000).…”

mentioning

confidence: 99%

N-Acylethanolamines Are Metabolized by Lipoxygenase and Amidohydrolase in Competing Pathways during Cottonseed Imbibition

et al. 2002

Self Cite

View full text Add to dashboard Cite

Saturated and unsaturated N-acylethanolamines (NAEs) occur in desiccated seeds primarily as 16C and 18C species with N-palmitoylethanolamine and N-linoleoylethanolamine (NAE 18:2) being most abundant. Here, we examined the metabolic fate of NAEs in vitro and in vivo in imbibed cotton (Gossypium hirsutum) seeds. When synthetic [1-14 C]Npalmitoylethanolamine was used as a substrate, free fatty acids (FFA) were produced by extracts of imbibed cottonseeds. When synthetic [1-14 C]NAE 18:2 was used as a substrate, FFA and an additional lipid product(s) were formed. On the basis of polarity, we presumed that the unidentified lipid was a product of the lipoxygenase (LOX) pathway and that inclusion of the characteristic LOX inhibitors nordihydroguaiaretic acid and eicosatetraynoic acid reduced its formation in vitro and in vivo. The conversion of NAE 18:2 in imbibed cottonseed extracts to 12-oxo-13-hydroxy-N-(9Z)-octadecanoylethanolamine was confirmed by gas chromatography-mass spectrometry, indicating the presence of 13-LOX and 13-allene oxide synthase, which metabolized NAE 18:2. Cell fractionation studies showed that the NAE amidohydrolase, responsible for FFA production, was associated mostly with microsomes, whereas LOX, responsible for NAE 18:2-oxylipin production, was distributed in cytosol-enriched fractions and microsomes. The highest activity toward NAE by amidohydrolase was observed 4 to 8 h after imbibition and by LOX 8 h after imbibition. Our results collectively indicate that two pathways exist for NAE metabolism during seed imbibition: one to hydrolyze NAEs in a manner similar to the inactivation of endocannabinoid mediators in animal systems and the other to form novel NAE-derived oxylipins. The rapid depletion of NAEs by these pathways continues to point to a role for NAE metabolites in seed germination.In mammalian cells, N-acylethanolamines (NAEs) have varied physiological roles. N-Arachidonylethanolamine (anandamide), a type of NAE in mammalian brain tissue, is an endogenous ligand for the cannabinoid receptor and modulates neurotransmission. Anandamide also can activate vanilloid (capsaicin) receptors and function as an endogenous analgesic (Pertwee, 2001), and appears to be involved in neuroprotection (Hansen et al., 2000;Van der Stelt et al., 2001). In other animal tissues, NAEs have been implicated in immunomodulation (Buckley et al., 2000), synchronization of embryo development (Paria and Dey, 2000), and induction of apoptosis (Sarker et al., 2000). These endogenous bioactive molecules termed "endocannabinoids" are hydrolyzed by fatty acid amidohydrolase (AHase) to terminate their signaling functions.In plants NAEs are present in substantial amounts in desiccated cotton (Gossypium hirsutum) seeds (1.6 g Ϫ1 g fresh weight), and their levels decline after a few hours of imbibition . Individual NAEs were identified predominantly as 16C and 18C species with N-palmitoylethanolamine (NAE 16:0) and N-linoleoylethanolamine (NAE 18:2) being the most abundant. NAEs in both plant and animal cells are deri...

show abstract

“…(22). Linoleoylethanolamide ((9Z,12Z)-octadeca-9,12-dienoylethanolamide; ODNHEtOH), linoleoylamide ((9Z,12Z)-octadeca-9,12-dienoylamide; ODNH 2 ), linoleoylmethylamide ((9Z,12Z)-octadeca-9,12-dienoylmethylamide; ODNHMe), and their 13-hydroxy derivatives (13-HODNHEtOH, 13-HODNH 2 , and 13-HODNHMe) were synthesized and characterized (purity Ͼ96% by gas-liquid chromatography) as reported (23). 15-Hydro(pero)xyanandamide (15-hydro(pero)xyeicosa-(5Z,8Z,11Z,13E)-tetraenoylethanolamide; 15-H(P)AnNH; purity Ͼ96%) and 11-hydro(pero)xyanandamide (11-H(P)AnNH; a mixture of 45% 11-H(P)AnNH, 24% 5-H(P)AnNH, 18% 15-H(P)AnNH, 9% 8/9-H(P)AnNH, and 4% 12-H(P)AnNH by reversed-phase high performance liquid chromatography) were a gift from Guus van Zadelhof (Bijvoet Center for Biomolecular Research, Utrecht University).…”

mentioning

confidence: 99%