Ethanol metabolism and acetaldehyde clearance: A multi-organ symphony.

Ethanol (EtOH) metabolism and acetaldehyde (AcH) clearance jointly constitute a systemic biological network, coordinated across multiple organs and cellular compartments, and profoundly shaped by physiological, genetic, and environmental contexts. This broader view challenges the conventional notion of the liver as the sole gatekeeper of EtOH oxidation and AcH detoxification. Here, we dissect the enzymatic dynamics of EtOH oxidation and AcH detoxification within the liver, emphasizing cell-type heterogeneity and metabolic zonation, and expand the lens to the gut, liver-gut axis, brain, and other extrahepatic organs. These distributed processes serve functions beyond EtOH oxidation and AcH detoxification: they orchestrate metabolite exchange, modulate drinking behavior, and fuel disease trajectories. Recognizing EtOH metabolism and AcH detoxification as a multi-organ network not only redefines its biological scope and reshapes how we understand alcohol-associated disorders but also offers new options for therapeutic intervention.