lipoxin-b4 and 5-15-dihydroperoxyeicosatetraenoic-acid

Chronic inflammation is now widely recognized to play important roles in many commonly occurring diseases, including COVID-19. The resolution response to this chronic inflammation is an active process governed by specialized pro-resolving mediators (SPMs) like the lipid mediators known as lipoxins. The biosynthesis of lipoxins is catalyzed by several lipoxygenases (LOXs) from arachidonic acid. However, the molecular details of the mechanisms involved are not well known yet. In this paper, we have combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations to analyze how reticulocyte 15-LOX-1 catalyzes the production of lipoxins from 5(

Topics: Arachidonate 15-Lipoxygenase; Biosynthetic Pathways; Catalysis; COVID-19; Humans; Inflammation; Leukotrienes; Lipid Peroxides; Lipoxins; Models, Molecular; Molecular Docking Simulation; Molecular Dynamics Simulation; Oxygen; Quantum Theory; Reticulocytes

Soybean lipoxygenase converted arachidonic acid to a group of polar products (lambda max, 300-301 nm), which were increasingly formed during the continued incubation at 20 degrees C after the initial incubation (2 hrs, at 4 degrees C). These products were identified as lipoxin A and B isomers, based on the chromatographic and spectrometric analyses. In further chromatographic analyses, the lipoxin A and B isomers were separated into at least three isomers, respectively. The exposure of 5,15-dihydroperoxyeicosatetraenoic acid to the soybean lipoxygenase produced the identical product profile of chromatography, substantiating the intermediacy of 5,15-dihydroperoxyeicosatetraenoic acid in the soybean lipoxygenase-catalyzed formation of lipoxins. Based on these results, it is proposed that the conversion of arachidonic acid into lipoxins by soybean lipoxygenase may bear a mechanistic resemblance to the formation of lipoxins in the human leukocytes.

Topics: Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Glycine max; Hydroxyeicosatetraenoic Acids; Isomerism; Leukotrienes; Lipid Peroxides; Lipoxins; Mass Spectrometry; Spectrophotometry, Ultraviolet

Topics: Animals; Arachidonate 12-Lipoxygenase; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acids; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Hydroxyeicosatetraenoic Acids; Leukocytes; Leukotrienes; Lipid Peroxides; Lipoxins; Spectrophotometry, Ultraviolet; Stereoisomerism; Substrate Specificity; Swine

Topics: Arachidonic Acids; Deoxyribose; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukocytes; Leukotrienes; Lipid Peroxides; Lipoxins; Stereoisomerism; Xylose

Arachidonate 12-lipoxygenase purified from porcine leukocytes shows 14R-oxygenase and 14, 15-leukotriene A synthase activities with 15-hydroperoxy-arachidonic acid as substrate. The enzyme transformed 5, 15-dihydroperoxy-arachidonic acid to several compounds with a conjugated tetraene. A major product was identified as 5S, 14R, 15S-trihydroperoxy-6, 10, 12-trans-8-cis-eicosatetraenoic acid, which was reduced to 5S, 14R, 15S-8-cis-lipoxin B. A requirement of molecular oxygen and the results of H2(18)O experiments suggested that formation of the latter compound was attributed mostly to the 14R-oxygenase activity of the enzyme. There were several other minor products identified as lipoxin A and B isomers. They were produced presumably by hydrolysis of 14, 15-epoxy compound formed by the leukotriene A synthase activity of 12-lipoxygenase.

Topics: Animals; Arachidonate 12-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Hydroxyeicosatetraenoic Acids; Leukocytes; Leukotrienes; Lipid Peroxides; Lipoxins; Oxygen; Swine