
-   The complex regulation of EPHX1 gene expression was originally attributed to the presence of alternative promoters [PMID: 9406998].
-   Expression of the mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5'-untranslated region in human ovary [PMID: 23564882].
-   Human EPHX1 expression in the liver is selectively driven by the proximal E1 promoter, but an alternative promoter region (E1-b promoter) drives expression in other tissues from both adult and fetal sources [PMID: 15465926].

## Summary

The EPHX1 gene, encoding for microsomal epoxide hydrolase (mEH), plays a critical role in detoxifying harmful epoxides, which are byproducts of the degradation of various compounds, including aromatic compounds and endogenous lipids [CS: 9]. In the liver, an organ central to detoxification and metabolism, the presence of toxic substances or the onset of disease conditions can lead to an increased production of harmful epoxides [CS: 8]. In response, the liver upregulates the expression of EPHX1 [CS: 8]. This upregulation serves to enhance the conversion of these harmful epoxides into less reactive and more water-soluble dihydrodiols, thereby facilitating their excretion from the body and mitigating potential damage [CS: 9].

Specifically, in conditions like cholestasis, where bile flow is impaired, there is an accumulation of bile acids and other potentially toxic substances in the liver [CS: 9]. This accumulation can lead to increased oxidative stress and the production of epoxides [CS: 8]. The elevated expression of EPHX1 in such conditions, as evidenced by its increased expression in Bsep (-/-) mice fed a cholic acid-enriched diet, indicates a direct response to counteract this toxic buildup [CS: 8]. By hydrolyzing the epoxides, EPHX1 aids in reducing the toxicity and oxidative stress in the liver, thus playing a protective role in maintaining liver function and health [CS: 9].
