Cytochrome P450 2E1 (CYP2E1) (CYP2E1)

Cytochrome P450 2E1 (CYP2E1) is a critical enzyme within the cytochrome P450 mixed-function oxidase system, primarily localized in the liver's endoplasmic reticulum and mitochondria [1.2.1, 1.3.3]. It is uniquely characterized by its high rate of uncoupled catalysis, which leads to the constitutive production of reactive oxygen species (ROS) such as superoxide and hydroxyl radicals even in the absence of substrates [1.1.5, 1.3.2]. This ROS generation initiates an oxidative stress pathway that causes significant cellular damage, including lipid peroxidation and DNA oxidation, contributing to the progression of alcoholic liver disease and non-alcoholic steatohepatitis [1.1.1, 1.2.3]. Beyond its role in ethanol metabolism, CYP2E1 is responsible for the bioactivation of various xenobiotics and drugs, most notably converting acetaminophen into the hepatotoxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) [1.2.1, 1.3.1]. The enzyme is also involved in endogenous processes like gluconeogenesis through the metabolism of acetone [1.2.1]. Due to its central role in oxidative stress and toxin bioactivation, CYP2E1 is considered a significant therapeutic target for preventing drug-induced liver injury and treating chronic metabolic liver diseases [1.2.2, 1.3.2]. Inhibitors of CYP2E1, such as chlormethiazole and diallyl sulfide, are being studied for their potential to mitigate these pathological effects [1.2.2, 1.4.1].

Other names

CYP2E [1.2.1]P450-J [1.2.1]P450C2E [1.2.1]CPE1 [1.2.1]Cytochrome P450 family 2 subfamily E member 1 [1.2.1]

Inhibition of the CYP2E1 enzyme to prevent the bioactivation of pro-toxins into reactive intermediates and to reduce the uncoupled production of reactive oxygen species (ROS) that drive oxidative stress and tissue injury [1.2.2, 1.3.2].