1-Nitropyrene Metabolism and Health Risk: Identification of Key Enzymes, Pathways, and Metabolites Using a Multimethod Approach.

ABSTRACT: Polycyclic aromatic hydrocarbon (PAH) derivatives have a widespread presence in the environment and even the human body, but their metabolism and potential risk remain unclear. In this study, we used molecular dynamics simulations and density functional theory to calculate the metabolic mechanism of 1-nitropyrene (1-NP), an important PAH derivative. The results showed that cytochrome P450 enzymes (CYPs) can metabolize 1-NP, with CYP 2A13 and CYP 2E1 being important enzyme isoforms, because they had lower binding affinities (-16.48 and -13.90 kcal/mol) to 1-NP than other CYPs (-2.38 to -7.89 kcal/mol). Additionally, these CYPs can metabolize 1-NP through epoxidation and hydroxylation pathways. Compared to hydroxylation, epoxidation had a lower energy barrier of 9.42 kcal/mol, and 4,5-epoxid

SUBMITTER: Wang M 

PROVIDER: S-EPMC11503755 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature