Inhibition of microsomal epoxide hydrolases by ureas, amides, and amines.
Chem Res Toxicol
; 14(4): 409-15, 2001 Apr.
Article
en En
| MEDLINE
| ID: mdl-11304129
ABSTRACT
The microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of xenobiotics such as polyaromatic toxicants. Additionally, polymorphism studies have underlined a potential role of this enzyme in relation to several diseases, such as emphysema, spontaneous abortion, and several forms of cancer. To provide new tools for studying the function of mEH, inhibition of this enzyme was investigated. Inhibition of recombinant rat and human mEH was achieved using primary ureas, amides, and amines. Several of these compounds are more potent than previously published inhibitors. Elaidamide, the most potent inhibitor that is obtained, has a K(i) of 70 nM for recombinant rat mEH. This compound interacts with the enzyme forming a noncovalent complex, and blocks substrate turnover through an apparent mix of competitive and noncompetitive inhibition kinetics. Furthermore, in insect cell cultures expressing rat mEH, elaidamide enhances the toxicity effects of epoxide-containing xenobiotics. These inhibitors could be valuable tools for investigating the physiological and toxicological roles of mEH.
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Base de datos:
MEDLINE
Asunto principal:
Urea
/
Inhibidores Enzimáticos
/
Epóxido Hidrolasas
/
Amidas
/
Aminas
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2001
Tipo del documento:
Article