An unstable [ti/2 at 37°= 32 L 2 (SD) sec] intermediate, thromboxane A2, was detected in the conversion of prostaglandin G2 into 841-hydroxy-3-oxopropyl)9,12L-di- Recently the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) were found to be the major metabolites of prostaglandin G2 (PGG2) in suspensions of human platelets (1, 2). Conversion of PGG2 into PHD was suggested to occur by rearrangement of the endoperoxide structure followed by incorporation of one molecule of H20 (1)

Hormone-triggered activation of the jasmonate signaling pathway in Arabidopsis thaliana requires SCF(COI1)-mediated proteasome degradation of JAZ repressors. (-)-JA-L-Ile is the proposed bioactive hormone, and SCF(COI1) is its likely receptor. We found that the biological activity of (-)-JA-L-Ile is unexpectedly low compared to coronatine and the synthetic isomer (+)-JA-L-Ile, which suggests that the stereochemical orientation of the cyclopentanone-ring side chains greatly affects receptor binding. Detailed GC-MS and HPLC analyses showed that the (-)-JA-L-Ile preparations currently used in ligand binding studies contain small amounts of the C7 epimer (+)-7-iso-JA-L-Ile. Purification of each of these molecules demonstrated that pure (-)-JA-L-Ile is inactive and that the active hormone is (+)-7-iso-JA-L-Ile, which is also structurally more similar to coronatine. In addition, we show that pH changes promote conversion of (+)-7-iso-JA-L-Ile to the inactive (-)-JA-L-Ile form, thus providing a simple mechanism that can regulate hormone activity through epimerization.

Trihydroxytetraenes, a novel series of oxygenated derivatives formed from arachidonic acid in human leukocytes, were recently isolated [Serhan, C. N., Hamberg, M. & Samuelsson, B. (1984) Biochem. Biophys. Res. Commun. 118, 943-949]. The structure of the major compound was established-i.e., 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid. The present study reports the structure of a second member of the trihydroxytetraene series of compounds-i.e., 5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid. When added to human neutrophils, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid stimulated superoxide anion generation and degranulation at submicromolar concentrations without provoking a substantial aggregation response. With respect to superoxide anion generation, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid proved to be as potent as leukotriene B4. In contrast, the compound was approximately 2 orders of magnitude less potent than either leukotriene B4 or fMet-LeuPhe at provoking degranulation. The results indicate that interaction(s) between the 5-and 15-lipoxygenase pathways of human leukocytes leads to formation of a new series of oxygenated derivatives of arachidonic acid that may be involved in regulating specific cellular responses. The trivial names lipoxin A (5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid) and lipoxin B (5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid) are proposed for the new compounds.

Arachidonic acid incubated with human platelets was converted into three compounds, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, 12L-hydroxy-5,8,-10-beptadecatrienoic acid, and the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid. The formation of the two latter compounds from arachidonic acid proceeded by pathways involving the enzyme, fatty acid cyclo-oxygenase, in the initial step and with the prostaglandin endoperoxide, PGG2, as an intermediate. The first mentioned compound was formed from 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid, which in turn was formed from arachidonic acid by the action of a novel lipoxygenase. Aspirin and indomethacin inhibited the fatty acid cyclo-oxygenase but not the lipoxygenase, whereas 5,8,11,14-eicosatetraynoic acid inhibited both enzymes. The almost exclusive transformation of the endoperoxide structure into nonprostaglandin derivatives supports the hypothesis that the endoperoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions. The observed transformations of arachidonic acid in platelets also explain the aggregating effect of this acid.Prostaglandins (PG) E2 and F2a are formed and released by human platelets during aggregation induced by various agents (3,4). This biosynthetic capacity has also been demonstrated with labeled precursors (5, 6).Recent work in our laboratory led to the isolation (1) of an earlier postulated (7) endoperoxide intermediate in prostaglandin biosynthesis. This finding was confirmed and extended in subsequent studies in which an additional endoperoxide derivative, carrying a hydroperoxy group at C-15, was isolated (2,8). Studies of the aggregation of human platelets also demonstrated that the biosynthetic process can stop at the endoperoxide stage resulting in release of the intermediates (PGG2 and/or PGH2) (2). Since the endoperoxides were found to be potent aggregating agents and since blockade of their formation is accompanied by inhibition of the second wave of aggregation, it was suggested that they play a physiological role in this process (2).In connection with these and other studies it became of particular interest to further investigate the transformation of arachidonic acid by human platelets. The present work demonstrates that arachidonic acid is oxygenated in this system both by the cyclo-oxygenase involved in prostaglandin [5,6,8,9,11,12,14,Arachidonic acid was prepared as described (10). 12-Hydroxyeicosanoic acid was prepared by anodic coupling of 10-acetoxyoctadecanoic acid [80 mg, prepared by acetylation of lO-hydroxyoctadecanoic acid (11)1 and methyl hydrogen succinate (300 mg). The product was hydrolyzed and subjected to silicic acid chromatography and preparative thin-layer chromatography, giving 30 mg (39%) of pure 12-hydroxyeicosanoic acid. Thin-layer chromatography of the methyl ester showed a single spot with RF = 0.57. Gasliquid chromatographic analysis of the methyl ester showed a single peak with equivalent c...

Plant oxylipins are a large family of metabolites derived from polyunsaturated fatty acids. The characterization of mutants or transgenic plants affected in the biosynthesis or perception of oxylipins has recently emphasized the role of the so-called oxylipin pathway in plant defense against pests and pathogens. In this context, presumed functions of oxylipins include direct antimicrobial effect, stimulation of plant defense gene expression, and regulation of plant cell death. However, the precise contribution of individual oxylipins to plant defense remains essentially unknown. To get a better insight into the biological activities of oxylipins, in vitro growth inhibition assays were used to investigate the direct antimicrobial activities of 43 natural oxylipins against a set of 13 plant pathogenic microorganisms including bacteria, oomycetes, and fungi. This study showed unequivocally that most oxylipins are able to impair growth of some plant microbial pathogens, with only two out of 43 oxylipins being completely inactive against all the tested organisms, and 26 oxylipins showing inhibitory activity toward at least three different microbes. Six oxylipins strongly inhibited mycelial growth and spore germination of eukaryotic microbes, including compounds that had not previously been ascribed an antimicrobial activity, such as 13-keto-9(Z),11(E),15(Z)-octadecatrienoic acid and 12-oxo-10,15(Z)-phytodienoic acid. Interestingly, this first large-scale comparative assessment of the antimicrobial effects of oxylipins reveals that regulators of plant defense responses are also the most active oxylipins against eukaryotic microorganisms, suggesting that such oxylipins might contribute to plant defense through their effects both on the plant and on pathogens, possibly through related mechanisms.