Nitric oxide regulates cytochrome P450 2D6 and 3A4 activity via concentration-dependent modulation of heme loading.

ABSTRACT: Cytochrome P450 enzymes (CYPs) play diverse roles in human health and disease, and although their activities depend on their heme contents, the cellular mechanisms governing CYP heme levels are unclear. Because CYP activities are influenced by biological nitric oxide (NO), we investigated how a range of NO exposures would impact the heme levels and activities of CYP2D6 and 3A4 expressed in Chinese hamster ovary cells and in the human liver cell line HepG2. Following expression, both CYPs were present as a 60:40 mix of heme-free and heme-bound forms. A low range of NO concentrations (approximately 1-10 nM) generated in cultures by a chemical NO donor or by added activated macrophages caused cells to allocate heme into their heme-free CYP3A4 and 2D6 populations such that the levels of heme-r

SUBMITTER: Das Sinha P 

PROVIDER: S-EPMC12605048 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature