Biochemical Aspects of the Hepatic Microsomal Ethanol-oxidizing System (MEOS): Resolved Initial Controversies and Updated Molecular Views

Rolf Teschke

doi:10.35248/2167-0501.19.8.267

Abstract

The hepatic microsomal ethanol-oxidizing system (MEOS) was initially confronted with much uncertainty, skepticism, scientific antagonism, and heavy discussions. Viewed as scientific challenges, this stimulated further research, and led to its successful separation from both, alcohol dehydrogenase and catalase, and its reconstitution that allowed defining the individual components of MEOS: cytochrome P450 (CYP), reductase, and phospholipids. Subsequently, it was challenging to elucidate the molecular basis of the microsomal ethanol oxidation. Unlike a usual dehydrogenation or simple oxidation process, ethanol oxidation via MEOS proceeds via reactive intermediates, commonly known as reactive oxygen species (ROS) and generated by various microsomal CYP isoenzymes including CYP 2E1, all of which are established components of MEOS. Due to its radical scavenging properties, ethanol combines with a small fraction of hydroxyl radicals and undergoes oxidation while the remaining radicals attack phospholipids of liver cell membranes. Chronic alcohol use enhances MEOS activity by upregulating CYP 2E1 combined with ROS generation, and thereby increases the metabolism of ethanol to acetaldehyde, its first metabolite with a high hepatotoxic potential. Considering the involvement of various CYP isoenzymes as constituents, MEOS is now best defined as a multi-CYP isoenzyme system, participating in ethanol metabolism and responsible for the molecular-based alcoholic liver disease.

Highlights

With its short chemical chain, alcohol attracts continuous interest in molecular sciences as illustrated by two processes, one of these molecular considerations relates to the production of alcohol and the other one focuses on its degradation [1,2,3,4,5,6]
In 1974, we found that bovine dismutase had only a small increasing effect on the activity of the isolated microsomal ethanol-oxidizing system (MEOS), not allowing suggestions of a possible involvement of superoxide radicals [25]
The use of different analytical approaches led occasionally to a variability of results and interpretations, the data can briefly be summarized as follows: (1) ethanol acts as a scavenger of hydroxyl radicals and undergoes oxidation to acetaldehyde during this molecular process; (2) hydroxyl radicals are generated through electron flow via the NADPH-dependent action of cytochrome P450 (CYP) 2E1 and other CYP isoenzymes, whereby additional forms of reactive oxygen species (ROS)

Summary

Introduction

With its short chemical chain, alcohol (syn. ethyl alcohol, ethanol, or in short EtOH) attracts continuous interest in molecular sciences as illustrated by two processes, one of these molecular considerations relates to the production of alcohol and the other one focuses on its degradation [1,2,3,4,5,6].

Results

Conclusion