Matches in SemOpenAlex for { <https://semopenalex.org/work/W3013119678> ?p ?o ?g. }
- W3013119678 abstract "ABSTRACT The oxylipins, 7S,14S-diHDHA and 7S,17S-diHDHA (RvD5), have been found in macrophages exudates and are believed to function as specialized pro-resolving mediators (SPM’s). Their biosynthesis is thought to proceed through sequential oxidations of docosahexaenoic acid (DHA) by lipoxygenase enzymes, specifically by h5-LOX first to 7S-HDHA, followed by h12-LOX to form 7S,14S-diHDHA or h15-LOX-1 to form 7S,17S-diHDHA (RvD5). In this work, we determined that oxidation of 7S-HpDHA to 7S,14S-diHDHA can be performed by either h12-LOX or h15-LOX-1, with similar kinetics. The oxidation at C14 of DHA by h12-LOX was expected, but the non-canonical reaction of h15-LOX-1 to make primarily 7S,14S-diHDHA was unexpected. Computer modeling suggests the alcohol on C7 of 7S-HDHA hydrogen bonds with the backbone carbonyl of I399, forcing the hydrogen abstraction from C12 to oxygenate on C14, and not C17. This result raised questions regarding synthesis of 7S,17S-diHDHA (RvD5). Strikingly, we find h15-LOX-2 oxygenates 7S-HDHA almost exclusively at C17, forming RvD5 with faster kinetics than h15-LOX-1. The presence of h15-LOX-2 in neutrophils and macrophages, suggests it may have a greater role in biosynthesizing SPM’s than previously thought. We also determined that the reactions of h5-LOX with 14S-HpDHA and 17S-HpDHA are kinetically slow compared to DHA, suggesting these may be minor biosynthetic routes in-vivo . Additionally, we show that 7S,14S-diHDHA and RvD5 have anti-aggregation properties with platelets at low micro-molar potencies, which could directly regulate clot resolution." @default.
- W3013119678 created "2020-04-03" @default.
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- W3013119678 date "2020-03-25" @default.
- W3013119678 modified "2023-09-23" @default.
- W3013119678 title "Altered specificity of 15-LOX-1 in the biosynthesis of 7S,14S-diHDHA implicates 15-LOX-2 in biosynthesis of resolvin D5" @default.
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- W3013119678 doi "https://doi.org/10.1101/2020.03.25.008573" @default.
- W3013119678 hasPublicationYear "2020" @default.
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