Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017:2017:4680732.
doi: 10.1155/2017/4680732. Epub 2017 Jan 10.

The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

W A García-Suástegui  1 , L A Ramos-Chávez  2 , M Rubio-Osornio  3 , M Calvillo-Velasco  3 , J A Atzin-Méndez  4 , J Guevara  5 , D Silva-Adaya  3
Affiliations
Review

The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

W A García-Suástegui et al. Oxid Med Cell Longev. 2017.

Abstract

Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there are no competing interests.

Figures

Figure 1
Figure 1
Exogenous agents and pathologies associated with CYP2E1 activity and expression in brain. LPS: lipopolysaccharide; MPP+: 1-methyl-4-phenylpyridinium; MPTP: 1-metil-4-fenil-1,2,3,6-tetrahydropyridine.
Figure 2
Figure 2
Ethanol oxidation by CYP2E1 results in an increase of ROS and oxidative stress. Ethanol can induce the expression/activity of CYP2E1 resulting in an increase of ROS and cellular damage. Increased ROS levels damage biomolecules such as lipid, protein, DNA, and mitochondria, starting a feedback cycle of ROS production-damage. ALD: aldehyde dehydrogenase; CYP2E1: cytochrome isoform 2E1; •OH: hydroxyl radical; •O2−: superoxide anion radical; H2O2: hydrogen peroxide; Fe2+: ferrous iron; NADPH: nicotinamide adenine dinucleotide phosphate (oxidized form); NADP+: nicotinamide adenine dinucleotide phosphate (reduced form).
See this image and copyright information in PMC

References

    1. Goodman L. S., Gilman A., Brunton L. L. Goodman & Gilman's Manual of Pharmacology and Therapeutics. New York, NY, USA: McGraw-Hill Medical; 2008.
    1. Lowndes H. E., Beiswanger C. M., Philbert M. A., Reuhl K. R. Substrates for neural metabolism of xenobiotics in adult and developing brain. NeuroToxicology. 1994;15(1):61–73. - PubMed
    1. Hodgson E. A. Textbook of Modern Toxicology. 3rd. John Wiley & Sons; 2004.
    1. Zhou S.-F., Liu J.-P., Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews. 2009;41(2):89–295. doi: 10.1080/03602530902843483. - DOI - PubMed
    1. Hodgson E., Levi P. E. Introduction to Biochemical Toxicology. 2nd. Norwalk, Conn, USA: Appleton & Lange; 1994.

Substances

LinkOut - more resources