Altered circulating endocannabinoids in anorexia nervosa during acute and weight-restored phases: A pilot study.

Anorexia nervosa (AN) is an eating disorder characterized by a low food intake and often exceeding exercise, leading to a particularly low body × weight proportion. Patients with AN usually report less hunger than healthy controls. Endogenous endocannabinoids (eCBs), specifically the anandamide, have been associated to hunger, as a meal initiator, but research regarding AN and eCB and inconclusive.

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

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.

Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase.

Hepoxilins are lipid signaling molecules derived from arachidonic acid through the 12-lipoxygenase pathway. These trans-epoxy hydroxy eicosanoids play a role in a variety of physiological processes, including inflammation, neurotransmission, and formation of skin barrier function. Mammalian hepoxilin hydrolase, partly purified from rat liver, has earlier been reported to degrade hepoxilins to trioxilins.

Directed evolution of an enantioselective epoxide hydrolase: uncovering the source of enantioselectivity at each evolutionary stage.

Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic kinetic resolution of racemic glycidyl phenyl ether.

Mammalian epoxide hydrolases in xenobiotic metabolism and signalling.

Epoxide hydrolases catalyse the hydrolysis of electrophilic--and therefore potentially genotoxic--epoxides to the corresponding less reactive vicinal diols, which explains the classification of epoxide hydrolases as typical detoxifying enzymes. The best example is mammalian microsomal epoxide hydrolase (mEH)-an enzyme prone to detoxification-due to a high expression level in the liver, a broad substrate selectivity, as well as inducibility by foreign compounds. The mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds.

Insights into the catalytic mechanism of human sEH phosphatase by site-directed mutagenesis and LC-MS/MS analysis.

We have recently reported that human soluble epoxide hydrolase (sEH) is a bifunctional enzyme with a novel phosphatase enzymatic activity. Based on a structural relationship with other members of the haloacid dehalogenase superfamily, the sEH N-terminal phosphatase domain revealed four conserved sequence motifs, including the proposed catalytic nucleophile D9, and several other residues potentially implicated in substrate turnover and/or Mg(2+) binding. To enlighten the catalytic mechanism of dephosphorylation, we constructed sEH phosphatase active-site mutants by site-directed mutagenesis.

Epoxide hydrolases: structure, function, mechanism, and assay.

Epoxide hydrolases are a class of enzymes important in the detoxification of genotoxic compounds, as well as in the control of physiological signaling molecules. This chapter gives an overview on the function, structure, and enzymatic mechanism of structurally characterized epoxide hydrolases and describes selected assays for the quantification of epoxide hydrolase activity.

Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function.

Epoxide hydrolases are vital to many organisms by virtue of their roles in detoxification, metabolism and processing of signaling molecules. The Mycobacterium tuberculosis genome encodes an unusually large number of epoxide hydrolases, suggesting that they might be of particular importance to these bacteria. We report here the first structure of an epoxide hydrolase from M.

Enhancing the enantioselectivity of an epoxide hydrolase by directed evolution.

[reaction: see text] The epoxide hydrolase (EH) from Aspergillus niger, which shows a selectivity factor of only E = 4.6 in the hydrolytic kinetic resolution of glycidyl phenyl ether, has been subjected to directed evolution for the purpose of enhancing enantioselectivity. After only one round of error-prone polymerase chain reaction (epPCR), enantioselectivity was more than doubled (E = 10.

The telltale structures of epoxide hydrolases.

Traditionally, epoxide hydrolases (EH) have been regarded as xenobiotic-metabolizing enzymes implicated in the detoxification of foreign compounds. They are known to play a key role in the control of potentially genotoxic epoxides that arise during metabolism of many lipophilic compounds. Although this is apparently the main function for the mammalian microsomal epoxide hydrolase (mEH), evidence is now accumulating that the mammalian soluble epoxide hydrolase (sEH), despite its proven role in xenobiotic metabolism, also has a central role in the formation and breakdown of physiological signaling molecules.

The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.

The mammalian soluble epoxide hydrolase (sEH) is an enzyme with multiple functions, being implicated in detoxification of xenobiotic epoxides as well as in regulation of physiological processes such as blood pressure. The enzyme is a homodimer, in which each subunit is composed of two domains. The 35-kDa C-terminal domain has an alpha/beta hydrolase fold and harbors the catalytic center for the EH activity.