Review Article Open Access
Volume 2 | Issue 1 | DOI: https://doi.org/10.33696/Gastroenterology.2.022

Alcoholic Liver Disease and the co-triggering Role of MEOS with Its CYP 2E1 Catalytic Cycle and ROS

  • 1Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/ Main, Frankfurt/Main, 63450 Hanau, Germany
  • 2In Vitro Drug Safety and Biotechnology & Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
  • 3Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, and Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA
  • 4Centre of Liver- and Alcohol Diseases, Ethanium Clinic Heidelberg, Germany
+ Affiliations - Affiliations

Corresponding Author

Rolf Teschke, rolf.teschke@gmx.de

Received Date: November 26, 2020

Accepted Date: January 20, 2021


Introduction: Alcohol or ethanol, as the correct chemical term, causes upon prolonged use in high amounts alcoholic liver disease (ALD), attributable to metabolic products and byproducts from enzymatic degradation of ethanol rather than to the relatively inert ethanol itself. The present review aimed to analyze mechanistic steps involved in ALD with a focus on molecular aspects related to the microsomal ethanol oxidizing system (MEOS), cytochrome P450 (CYP) 2E1, and ROS (reactive oxygen species). Apart from alcohol dehydrogenase (ADH), hepatic metabolism proceeds also via MEOS, which functions independently from ADH and catalase. MEOS is dependent upon various CYP isoforms with a preference of the CYP 2E1 isoform and requires not only NADPH + H+ as cofactor but also molecular oxygen. During alcohol metabolism via MEOS and CYP 2E1, and due to incomplete split of oxygen within the catalytic CYP 2E1 cycle, reactive oxygen species (ROS) are generated as toxic byproducts such as ethoxy radical CH3CH2O•, hydroxyethyl radical CH3C(•)HOH, acetyl radical CH3CHO•, single radical 1O2, superoxide radical HO•2, hydrogen peroxide H2O2, hydroxyl radical HO•, alkoxyl radical RO•, and peroxyl radical ROO•. Under mechanistic aspects, convincing evidence suggests that microsomal oxidative stress by radicals generated in liver microsomes through CYP 2E1 is directly involved in triggering early stages of ALD such as alcoholic fatty liver disease. Microsomal oxidative stress is also indirectly responsible for late stages of ALD such as liver cirrhosis, likely via modification of the immune system. In addition, radicals are generated by CYP 2E1 also in liver mitochondria causing mitochondrial oxidative stress and in the mucosa of the intestinal tract, suggesting some cotriggering pathogenetic role especially via endotoxins derived from the gut microbiome. In conclusion, MEOS, CYP 2E1, and ROS are primarily involved in triggering ALD via radical based toxic effects and alterations of the immune system.


Alcoholic liver disease, Cytochrome P450 2E1, Endotoxins, Gut microbiome, Lipopolysaccharides, Microsomal ethanol oxidizing system, Microsomal oxidative stress, Mitochondrial oxidative stress, Reactive oxygen species

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