Microsomal Ethanol‐Oxidizing System: Success Over 50 Years and an Encouraging Future

Fifty years ago, in 1968, the pioneering scientists Charles S. Lieber and Leonore M. DeCarli discovered the capacity for liver microsomes to oxidize ethanol (EtOH) and named it the microsomal ethanol‐oxidizing system ( MEOS ), which revolutionized clinical and experimental alcohol research. The last 50 years of MEOS are now reviewed and highlighted. Since its discovery and as outlined in a plethora of studies, significant insight was gained regarding the fascinating nature of MEOS : (i) MEOS is distinct from alcohol dehydrogenase and catalase, representing a multienzyme complex with cytochrome P450 ( CYP ) and its preferred isoenzyme CYP 2E1, NADPH –cytochrome P450 reductase, and phospholipids; (ii) it plays a significant role in alcohol metabolism at high alcohol concentrations and after induction due to prolonged alcohol use; (iii) hydroxyl radicals and superoxide radicals promote microsomal EtOH oxidation, assisted by phospholipid peroxides; (iv) new aspects focus on microsomal oxidative stress through generation of reactive oxygen species ( ROS ), with intermediates such as hydroxyethyl radical, ethoxy radical, acetyl radical, singlet radical, hydroxyl radical, alkoxyl radical, and peroxyl radical; (v) triggered by CYP 2E1, ROS are involved in the initiation and perpetuation of alcoholic liver injury, consequently shifting the previous nutrition‐based concept to a clear molecular‐based disease; (vi) intestinal CYP 2E1 induction and ROS are involved in endotoxemia, leaky gut, and intestinal microbiome modifications, together with hepatic CYP 2E1 and liver injury; (vii) circulating blood CYP 2E1 exosomes may be of diagnostic value; (viii) circadian rhythms provide high MEOS activities associated with significant alcohol metabolism and potential toxicity risks as a largely neglected topic; and (ix) a variety of genetic animal models are useful and have been applied elucidating mechanistic aspects of MEOS . In essence, MEOS along with its CYP 2E1 component currently explains several mechanistic steps leading to alcoholic liver injury and has a promising future in alcohol research.