Recent preclinical studies have questioned the traditional view that the liver metabolizes most systemic acetaldehyde (105, 123). Compared to mice with a global alcohol dehydrogenase 2 gene knockout (Aldh2), which exhibit remarkably higher blood acetaldehyde concentrations following acute oral alcohol administration than wild-type controls, mice with hepatocyte-specific Aldh2 deletion showed only about a 50% increase in systemic acetaldehyde (123). Follow-up studies revealed that the combined deletion of Aldh2 in both the liver and gut raised acetaldehyde concentrations to those measured in global Aldh2 knockouts after alcohol exposure (105).
