CYP2E1

Overview

CYP2E1 is a member of the cytochrome P450 superfamily of enzymes. These enzymes are involved in the metabolism of various substances within the body, including drugs, toxins, and endogenous compounds. CYP2E1 is particularly known for its role in the metabolism of small organic molecules, such as ethanol, acetone, and benzene.

Structure

Active site of CYP2E1

CYP2E1 is a heme-thiolate protein, which means it contains a heme group that is essential for its enzymatic activity. The active site of CYP2E1, as shown in the image, is where substrate binding and catalysis occur. The structure of CYP2E1 allows it to interact with a variety of small molecules, facilitating their conversion into more water-soluble forms for excretion.

Function

CYP2E1 plays a critical role in the metabolism of several important substances:

• Ethanol metabolism: CYP2E1 is induced by ethanol and contributes to its oxidation to acetaldehyde, especially at high concentrations of ethanol.
• Drug metabolism: It is involved in the metabolism of several drugs, including paracetamol (acetaminophen), where it contributes to the formation of toxic metabolites.
• Toxin metabolism: CYP2E1 metabolizes various toxins and procarcinogens, such as nitrosamines and carbon tetrachloride.

Regulation

The expression and activity of CYP2E1 are regulated by several factors:

• Induction by ethanol: Chronic alcohol consumption leads to increased expression of CYP2E1.
• Dietary factors: Fasting and a high-fat diet can also induce CYP2E1 expression.
• Hormonal regulation: Hormones such as insulin and glucagon can influence CYP2E1 activity.

Clinical Significance

CYP2E1 is clinically significant due to its role in drug interactions and toxicity:

• Drug interactions: Induction of CYP2E1 can alter the metabolism of co-administered drugs, leading to potential drug interactions.
• Toxicity: Overexpression or increased activity of CYP2E1 can lead to enhanced production of toxic metabolites, contributing to liver damage and other adverse effects.

Related pages

• Cytochrome P450
• Ethanol metabolism
• Drug metabolism