2026-10-15T10:16:43Z https://data.mendeley.com/oai

oai:data.mendeley.com/zpy7phww4b.1 2025-06-16T23:22:08Z

zhou, xue Epoxide hydrolases are involved in the metabolism of 5(6)-epoxyeicosatrienoic acid Mendeley Data Epoxyeicosatrienoic acids (EETs) have garnered extensive research interest as crucial signaling mediators that regulate key biological processes, including inflammation, pain and angiogenesis. While the metabolism of 8(9)-, 11(12)-, and 14(15)-EET has been well established to be metabolized in the presence of epoxide hydrolases, primarily soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH), the fate of 5(6)-EET was previously thought to be limited to its spontaneous chemical conversion into 5,6-dihydroxyeicosatrienoic acid (5,6-DHET) lactone. Here, we reported that the metabolism of 5(6)-EET is also enzymatically regulated by both sEH and mEH, occurring in parallel with its chemical formation to 5,6-DHET lactone. Specifically, in an epoxide hydrolases-free system, 5(6)-EET was rapidly converted to 5,6-DHET lactone, whereas 14(15)-EET remained relatively stable. In contrast, in a cellular system, EPHX2 (encodes sEH) knockout and EPHX1 (encodes mEH) knockout significantly attenuated 5(6)-EET degradation, indicating that both sEH and mEH actively mediate the metabolism of 5(6)-EET. Moreover, we observed that 5(6)-EET underwent conversion to 5,6-DHET lactone within the cellular environment as well. This study provides direct evidence that enzymatic metabolism of 5(6)-EET by epoxide hydrolases occurs concurrently with its spontaneous chemical transformation. This study expands our understanding of 5(6)-EET metabolism and reveals a previously unrecognized role of epoxide hydrolases in modulating relevant biological fate. Metabolomics Dataset doi:10.17632/zpy7phww4b.1 oai:data.mendeley.com/zpy7phww4b.1 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/zpy7phww4b 2025-06-16T23:22:08Z