Publications

• EH3 (ABHD9): the first member of a new epoxide hydrolase family with high activity for fatty acid epoxides.

  Decker M., Adamska M., Cronin A., Di Giallonardo F., Burgener J., Marowsky A., Falck J.R., Morisseau C., Hammock B.D., Gruzdev A., Zeldin D.C., Arand M.

  Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules. Here, we report the identification of two human epoxide hydrolases: EH3 and EH4. They sha ... >> More

  Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules. Here, we report the identification of two human epoxide hydrolases: EH3 and EH4. They share 45% sequence identity, thus representing a new family of mammalian epoxide hydrolases. Quantitative RT-PCR from mouse tissue indicates strongest EH3 expression in lung, skin, and upper gastrointestinal tract. The recombinant enzyme shows a high turnover number with 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET), as well as 9,10-epoxyoctadec-11-enoic acid (leukotoxin). It is inhibited by a subclass of N,N'-disubstituted urea derivatives, including 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, 1-cyclohexyl-3-dodecylurea, and 1-(1-acetylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea, compounds so far believed to be selective inhibitors of mammalian soluble epoxide hydrolase (sEH). Its sensitivity to this subset of sEH inhibitors may have implications on the pharmacologic profile of these compounds. This is particularly relevant because sEH is a potential drug target, and clinical trials are under way exploring the value of sEH inhibitors in the treatment of hypertension and diabetes type II. << Less

  J. Lipid Res. 53:2038-2045(2012) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria.

  Madacki J., Laval F., Grzegorzewicz A., Lemassu A., Zahorszka M., Arand M., McNeil M., Daffe M., Jackson M., Laneelle M.A., Kordulakova J.

  Mycolic acids are the hallmark of the cell envelope in mycobacteria, which include the important human pathogens <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium leprae</i> Mycolic acids are very long C60-C90 α-alkyl β-hydroxy fatty acids having a variety of functional groups on their hydroc ... >> More

  Mycolic acids are the hallmark of the cell envelope in mycobacteria, which include the important human pathogens <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium leprae</i> Mycolic acids are very long C60-C90 α-alkyl β-hydroxy fatty acids having a variety of functional groups on their hydrocarbon chain that define several mycolate types. Mycobacteria also produce an unusually large number of putative epoxide hydrolases, but the physiological functions of these enzymes are still unclear. Here, we report that the mycobacterial epoxide hydrolase EphD is involved in mycolic acid metabolism. We found that orthologs of EphD from <i>M. tuberculosis</i> and <i>M. smegmatis</i> are functional epoxide hydrolases, cleaving a lipophilic substrate, 9,10-<i>cis</i>-epoxystearic acid, <i>in vitro</i> and forming a vicinal diol. The results of EphD overproduction in <i>M. smegmatis</i> and <i>M. bovis</i> BCG Δ<i>hma</i> strains producing epoxymycolic acids indicated that EphD is involved in the metabolism of these forms of mycolates in both fast- and slow-growing mycobacteria. Moreover, using MALDI-TOF-MS and ¹H NMR spectroscopy of mycolic acids and lipids isolated from EphD-overproducing <i>M. smegmatis</i>, we identified new oxygenated mycolic acid species that accumulated during epoxymycolate depletion. Disruption of the <i>ephD</i> gene in <i>M. tuberculosis</i> specifically impaired the synthesis of ketomycolates and caused accumulation of their precursor, hydroxymycolate, indicating either direct or indirect involvement of EphD in ketomycolate biosynthesis. Our results clearly indicate that EphD plays a role in metabolism of oxygenated mycolic acids in mycobacteria. << Less

  J Biol Chem 293:5172-5184(2018) [PubMed] [EuropePMC]