Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse
Figure 3
(a) Effect of ethanol dose on liver ADH activity. Three mice were sacrificed at scheduled times during ethanol metabolism after various doses of ethanol: 0.5, 1, and 2 h for 1 and 2 g/kg (9 mice in each dose); 0.5, 1, 2, 4, and 8 h for 3 g/kg (15 mice in the dose); 0.5, 1. 2, 4, 8, and 12 h for 0, 4.5, and 5.0 g/kg (18 mice in each dose), and livers were then removed to prepare liver extracts. The liver ADH activity was measured by the conventional assay with 15 mM ethanol as a substrate at pH 10.7 using liver extracts and is expressed in terms of liver weight/kg body weight. The activities were averaged in each group of ethanol dose to obtain the mean ± SD. (b) Effect of ethanol dose on ADH 1 (○) and ADH 3 (⚫) content of liver. In addition to liver ADH activity, the liver extracts were used to measure ADH isozyme contents by EIA using isozyme-specific antibodies. Liver ADH isozyme contents were also averaged in each group of ethanol dose to obtain the mean ± SD. (c) Effect of ethanol dose on ratio of ADH 3 content to ADH 1 content.
