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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-20989

Deckert, M; Arand, M; Cronin, A (2009). Mammalian epoxide hydrolases in xenobiotic metabolism and signalling. Archives of Toxicology, 83(4):297-318.

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Abstract

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. Furthermore, evidence is accumulating that mammalian epoxide hydrolases play physiological roles other than detoxification, particularly through involvement in signalling processes. This certainly holds true for soluble epoxide hydrolase (sEH) whose main function seems to be the turnover of lipid derived epoxides, which are signalling lipids with diverse functions in regulatory processes, such as control of blood pressure, inflammatory processes, cell proliferation and nociception. In recent years, the sEH has attracted attention as a promising target for pharmacological inhibition to treat hypertension and possibly other diseases. Recently, new hitherto uncharacterised epoxide hydrolases could be identified in mammals by genome analysis. The expression pattern and substrate selectivity of these new epoxide hydrolases suggests their participation in signalling processes rather than a role in detoxification. Taken together, epoxide hydrolases (1) play a central role in the detoxification of genotoxic epoxides and (2) have an important function in the regulation of physiological processes by the control of signalling molecules with an epoxide structure.

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:April 2009
Deposited On:29 Sep 2009 10:52
Last Modified:31 Dec 2013 08:47
Publisher:Springer
ISSN:0340-5761
Publisher DOI:10.1007/s00204-009-0416-0
PubMed ID:19340413
Citations:Web of Science®. Times Cited: 54
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