MEOS, which involves cytochrome P450 enzymes (CYP2E1) in the endoplasmic reticulum, has a lower affinity for alcohol compared to ADH, making it less involved in the metabolism of moderate alcohol exposures. However, its key enzyme, CYP2E1, is upregulated by chronic alcohol consumption, increasing its role in metabolizing larger alcohol doses (90). For instance, animals fed a liquid diet with 36% of calories from ethanol showed a 7.5-fold increase in liver microsomal CYP2E compared to nonethanol pair-fed controls. Similarly, CYP2E1 content was found to be 4 times higher in liver biopsies from men with an AUD than in those from men who reported abstaining from heavy alcohol consumption (114). This upregulation of CYP2E1 explains, in part, the metabolic tolerance to alcohol and the cross-tolerance to other drugs that are also substrates of CYP2E1, such as pentobarbital and diazepam, in people with AUD (90).
