बायोकैमिस्ट्री और फार्माकोलॉजी: ओपन एक्सेस

बायोकैमिस्ट्री और फार्माकोलॉजी: ओपन एक्सेस
खुला एक्सेस

आईएसएसएन: 2167-0501

अमूर्त

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

Rolf Teschke*

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.

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