CYP2E1

Cytochrome P450, family 2, subfamily E, polypeptide 1
Rendering based on PDB 3E4E.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3E4E, 3E6I, 3GPH, 3KOH, 3LC4, 3T3Z
Identifiers
Symbols	CYP2E1 ; CPE1; CYP2E; P450-J; P450C2E
External IDs	OMIM: 124040 MGI: 88607 HomoloGene: 68089 ChEMBL: 5281 GeneCards: CYP2E1 Gene
EC number	1.14.13.n7
Gene ontology Molecular function • monooxygenase activity • iron ion binding • arachidonic acid epoxygenase activity • steroid hydroxylase activity • oxidoreductase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen • oxygen binding • enzyme binding • heme binding Cellular component • Golgi membrane • cytoplasm • mitochondrion • endoplasmic reticulum membrane • intrinsic component of endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • triglyceride metabolic process • xenobiotic metabolic process • steroid metabolic process • response to ozone • response to organonitrogen compound • monoterpenoid metabolic process • drug metabolic process • epoxygenase P450 pathway • exogenous drug catabolic process • small molecule metabolic process • response to ethanol • heterocycle metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1571	13106
Ensembl	ENSG00000130649	ENSMUSG00000025479
UniProt	P05181	Q05421
RefSeq (mRNA)	NM_000773	NM_021282
RefSeq (protein)	NP_000764	NP_067257
Location (UCSC)	Chr 10: 133.52 – 133.56 Mb	Chr 7: 140.76 – 140.77 Mb
PubMed search	[1]	[2]

Cytochrome P450 2E1 (abbreviated CYP2E1, EC 1.14.13.n7), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene. While it is involved in the oxidative metabolism of a small range of substrates (mostly small polar molecules), there are many important drug interactions mediated by CYP2E1.

Function

Most drugs undergo deactivation by CYP2E1, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYP2E1 to form their active compounds (for examples - see table below)

CYP2E1, as well as alcohol dehydrogenase and aldehyde dehydrogenase, is an important enzyme for the conversion of ethanol to acetaldehyde and to acetate in humans.

In the conversion sequence of acetyl-CoA to glucose, CYP2E1 transforms acetone via hydroxyacetone (acetol) into propylene glycol and methylglyoxal, the precursors of pyruvate, acetate and lactate.

Ligands

Following is a table of selected substrates, inducers and inhibitors of CYP2E1. Where classes of agents are listed, there may be exceptions within the class.

Selected inducers, inhibitors and substrates of CYP2E1

Substrates	Inhibitors	Inducers
anaesthetics: halothane enflurane isoflurane methoxyflurane sevoflurane paracetamol (acetaminophen) - used as analgesic, antipyretic - toxication by CYP2E1 ethanol (psychoactive) Industrial potentially toxic substances aniline benzene dimethylformamide theophylline (stimulant, active metabolite of caffeine) chlorzoxazone (muscle relaxant) Zopiclone and Eszopiclone (sedative/hypnotics)	diethyldithiocarbamate (in cancer) disulfiram (in alcoholism)	ethanol (psychoactive) isoniazid (in tuberculosis) tobacco smoking

Regulation

Within one day of birth, the rat hepatic CYP2E1 gene is activated transcriptionally. CYP2E1 expression is easily inducible. It seems that there exist two stages of induction, a posttranslational mechanism for increased protein stability at low levels of ethanol and an additional transcriptional induction at high levels of ethanol.

Applications

Trees have been genetically engineered to overexpress the CYP2E1 enzyme. These transgenic trees have been used to remove pollutants from groundwater, a process known as phytoremediation.

See also

• Cytochrome
• Metabolism