It is widely known that ethanol (ETOH) modulates the activity of the mixed function mono-oxygenase (MFO) system. How this drug metabolizing system changes upon ETOH withdrawal is unclear, thus it was the purpose of our study to characterize possible changes by investigating activities of individual MFO isozymes. Enzymatic and immunochemical analyses revealed an ethanol inducible isozyme, CYP2E1, is rapidly degraded following withdrawal in several tissues, including brain, liver, kidney, and intestine. This suggests that any residual enhancement of ETOH clearance after ETOH withdrawal cannot be due to an increase in CYP2E1 activity. In contrast, other ETOH inducible isoforms of the MFO system remained transiently elevated following withdrawal, suggesting their mechanism of regulation differs to that of CYP2E1.
