Review Epoxide hydrolases: their roles and interactions with lipid metabolism John W. Newman, Christophe Morisseau, Bruce D. Hammock * Department of Entomology, UCDavis Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, USA Abstract The epoxide hydrolases (EHs) are enzymes present in all living organisms, which transform epoxide con- taining lipids by the addition of water. In plants and animals, many of these lipid substrates have potent biologically activities, such as host defenses, control of development, regulation of inflammation and blood pressure. Thus the EHs have important and diverse biological roles with profound effects on the physiolog- ical state of the host organisms. Currently, seven distinct epoxide hydrolase sub-types are recognized in higher organisms. These include the plant soluble EHs, the mammalian soluble epoxide hydrolase, the hep- oxilin hydrolase, leukotriene A 4 hydrolase, the microsomal epoxide hydrolase, and the insect juvenile hor- mone epoxide hydrolase. While our understanding of these enzymes has progressed at different rates, here we discuss the current state of knowledge for each of these enzymes, along with a distillation of our current understanding of their endogenous roles. By reviewing the entire enzyme class together, both commonali- ties and discrepancies in our understanding are highlighted and important directions for future research pertaining to these enzymes are indicated. Ó 2004 Elsevier Ltd. All rights reserved. 0163-7827/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.plipres.2004.10.001 * Corresponding author. Tel.: +1 530 752 7519; fax: +1 530 752 1537. E-mail address: bdhammock@ucdavis.edu (B.D. Hammock). Progress in Lipid Research 44 (2005) 1–51 Progress in Lipid Research www.elsevier.com/locate/plipres