Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β-oxidation-like pathway resulting in acrylyl-CoA conjugate buildup.

ABSTRACT: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that induces diverse biological and toxic effects, including reprogramming intermediate metabolism, mediated by the aryl hydrocarbon receptor. However, the specific reprogramming effects of TCDD are unclear. Here, we performed targeted LC-MS analysis of hepatic extracts from mice gavaged with TCDD. We detected an increase in S-(2-carboxyethyl)-L-cysteine, a conjugate from the spontaneous reaction between the cysteine sulfhydryl group and highly reactive acrylyl-CoA, an intermediate in the cobalamin (Cbl)-independent β-oxidation-like metabolism of propionyl-CoA. TCDD repressed genes in both the canonical Cbl-dependent carboxylase and the alternate Cbl-independent β-oxidation-like pathways as well as inhibit

SUBMITTER: Orlowska K 

PROVIDER: S-EPMC9418907 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature