Acetone catabolism by cytochrome P450 2E1: Studies with CYP2E1-null mice

Previous experiments in vitro have suggested that cytochrome P450 2E1 (CYP2 E1) is involved in acetone catabolism by converting acetone to acetol and t hen to methylglyoxal, both intermediates in the gluconeogenic pathway. In t he present study, CYP2E1-null mice were used to demonstrate the role of CYP ZE1 in acetone catabolism in vivo. The blood acetone level in male CYP2E1-n ull mice was 3.3 +/- 0.9 mu g/mL, which was similar to levels of their sex- and age-matched parental lineage strains C57BL/6N (2.3 +/- 0.2 mu g/mL) an d 129/Sv (3.5 +/- 0.3 mu g/mL) mice (both are CYP2E1wild-type). After fasti ng for 48 hr, the blood acetone levels in the CYP2E1 wild-type mice were in creased by 2.5- to 4.4-fold, but that in the CYP2E1-null mice increased 28- fold. These results clearly demonstrate that CYPZE1 plays a vital role in t he catabolism of acetone under fasting conditions. (C) 1999 Elsevier Scienc e Inc.