ArticleToxicology2015
Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates.
Article in Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Human mitochondrial CYP2E1-mediated styrene metabolism increases oxidative stress and impairs antioxidant rescue in Caenorhabditis elegans.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2025Article
- Subcellular expression of CYP2E1 in HepG2 cells impacts response to free oleic and palmitic acid.Current research in toxicology · 2024Article
- An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment.International journal of molecular sciences · 2023Review
- Review
- Zebrafish have an ethanol-inducible hepatic 4-nitrophenol hydroxylase that is not CYP2E1-like.Environmental toxicology and pharmacology · 2017Article
- 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice.Toxicology · 2017Article
- Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.Journal of clinical and translational research · 2017Article
- Triptolide Induces hepatotoxicity via inhibition of CYP450s in Rat liver microsomes.BMC complementary and alternative medicine · 2017Article
- Toxicological Implications of Mitochondrial Localization of CYP2E1.Toxicology research · 2017Article
- Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes.International journal of environmental research and public health · 2016Article
- Roles of Cytochrome P450 in Metabolism of Ethanol and Carcinogens.Advances in experimental medicine and biologyReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cytochrome P450 2E1 (CYP2E1) detoxifies or bioactivates many low molecular-weight compounds. Most knowledge about CYP2E1 activity relies on studies of the enzyme localized to endoplasmic reticulum (erCYP2E1); however, CYP2E1 undergoes transport to mitochondria (mtCYP2E1) and becomes metabolically active. We report the first comparison of in vitro steady-state kinetic profiles for erCYP2E1 and mtCYP2E1 oxidation of probe substrate 4-nitrophenol and pollutants styrene and aniline using subcellular fractions from rat liver. For all substrates, metabolic efficiency changed with substrate concentration for erCYP2E1 reflected in non-hyperbolic kinetic profiles but not for mtCYP2E1. Hyperbolic kinetic profiles for the mitochondrial enzyme were consistent with Michaelis-Menten mechanism in which metabolic efficiency was constant. By contrast, erCYP2E1 metabolism of 4-nitrophenol led to a loss of enzyme efficiency at high substrate concentrations when substrate inhibited the reaction. Similarly, aniline metabolism by erCYP2E1 demonstrated negative cooperativity as metabolic efficiency decreased with increasing substrate concentration. The opposite was observed for erCYP2E1 oxidation of styrene; the sigmoidal kinetic profile indicated increased efficiency at higher substrate concentrations. These mechanisms and CYP2E1 levels in mitochondria and endoplasmic reticulum were used to estimate the impact of CYP2E1 subcellular localization on metabolic flux of pollutants. Those models showed that erCYP2E1 mainly carries out aniline metabolism at all aniline concentrations. Conversely, mtCYP2E1 dominates styrene oxidation at low styrene concentrations and erCYP2E1 at higher concentrations. Taken together, subcellular localization of CYP2E1 results in distinctly different enzyme activities that could impact overall metabolic clearance and/or activation of substrates and thus impact the interpretation and prediction of toxicological outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.