54232-59-6Relevant articles and documents
Dehydrogenase reductase 9 (SDR9C4) and related homologs recognize a broad spectrum of lipid mediator oxylipins as substrates
Belyaeva, Olga V.,Boeglin, William E.,Brash, Alan R.,Goggans, Kelli R.,Karki, Suman,Kedishvili, Natalia Y.,Popov, Kirill M.,Wendell, Stacy G.,Wirth, Samuel E.
, (2022/01/31)
Bioactive oxylipins play multiple roles during inflammation and in the immune response, with termination of their actions partly dependent on the activity of yet-to-be characterized dehydrogenases. Here, we report that human microsomal dehydrogenase reductase 9 (DHRS9, also known as SDR9C4 of the short-chain dehydrogenase/reductase (SDR) superfamily) exhibits a robust oxidative activity toward oxylipins with hydroxyl groups located at carbons C9 and C13 of octadecanoids, C12 and C15 carbons of eicosanoids, and C14 carbon of docosanoids. DHRS9/SDR9C4 is also active toward lipid inflammatory mediator dihydroxylated Leukotriene B4 and pro-resolving mediators such as tri-hydroxylated Resolvin D1 and Lipoxin A4, although notably, with lack of activity on the 15-hydroxyl of prostaglandins. We also found that the SDR enzymes phylogenetically related to DHRS9, i.e., human SDR9C8 (or retinol dehydrogenase 16), the rat SDR9C family member known as retinol dehydrogenase 7, and the mouse ortholog of human DHRS9 display similar activity toward oxylipin substrates. Mice deficient in DHRS9 protein are viable, fertile, and display no apparent phenotype under normal conditions. However, the oxidative activity of microsomal membranes from the skin, lung, and trachea of Dhrs9?/? mice toward 1 μM Leukotriene B4 is 1.7- to 6-fold lower than that of microsomes from wild-type littermates. In addition, the oxidative activity toward 1 μM Resolvin D1 is reduced by about 2.5-fold with DHRS9-null microsomes from the skin and trachea. These results strongly suggest that DHRS9 might play an important role in the metabolism of a wide range of bioactive oxylipins in vivo.
Oxidation of C18 Hydroxy-Polyunsaturated Fatty Acids to Epoxide or Ketone by Catalase-Related Hemoproteins Activated with Iodosylbenzene
Teder, Tarvi,Boeglin, William E.,Brash, Alan R.
, p. 587 - 597 (2017/06/30)
Small catalase-related hemoproteins with a facility to react with fatty acid hydroperoxides were examined for their potential mono-oxygenase activity when activated using iodosylbenzene. The proteins tested were a Fusarium graminearum 41?kD catalase hemoprotein (Fg-cat, gene FGSG_02217), a Pseudomonas fluorescens Pfl01 catalase (37.5?kD, accession number WP_011333788.1), and a Mycobacterium avium ssp. paratuberculosis 33?kD catalase (gene MAP-2744c). 13-Hydroxy-octadecenoic acids (which are normally unreactive) were selected as substrates because these enzymes react specifically with the corresponding 13S-hydroperoxides (Pakhomova et al. 18:2559–2568, 5; Teder et al. 1862:706–715, 14). In the presence of iodosylbenzene Fg-cat converted 13S-hydroxy-fatty acids to two products: the 15,16-double bond of 13S-hydroxy α-linolenic acid was oxidized stereospecifically to the 15S,16R-cis-epoxide or the 13-hydroxyl was oxidized to the 13-ketone. Products were identified by UV, HPLC, LC–MS, NMR and by comparison with authentic standards prepared for this study. The Pfl01-cat displayed similar activity. MAP-2744c oxidized 13S-hydroxy-linoleic acid to the 13-ketone, and epoxidized the double bonds to form the 9,10-epoxy-13-hydroxy, 11,12-epoxy-13-hydroxy, and 9,10-epoxy-13-keto derivatives; equivalent transformations occurred with 9S-hydroxy-linoleic acid as substrate. In parallel incubations in the presence of iodosylbenzene, human catalase displayed no activity towards 13S-hydroxy-linoleic acid, as expected from the highly restricted access to its active site. The results indicated that with suitable transformation to Compound I, monooxygenase activity can be demonstrated by these catalase-related hemoproteins with tyrosine as the proximal heme ligand.
Physcomitrella patens has lipoxygenases for both eicosanoid and octadecanoid pathways
Anterola, Aldwin,G?bel, Cornelia,Hornung, Ellen,Sellhorn, George,Feussner, Ivo,Grimes, Howard
experimental part, p. 40 - 52 (2009/07/11)
Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 α-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering p
