The objective of this project is to evaluate the role of liver alcohol dehydrogenase and aldehyde dehydrogenase in the regulation of alcohol metabolism in various nutritional or physiologic states. We have shown that fasting of rats or hamsters for 48th results in a concominant decrease of both ethanol elimination rate in vivo and of the maximal alcohol dehydrogenase activity measured in vitro. Since NAD ion/NADH ratios were shown to be similar in fed and fasted animals following ethanol administration, the decrease in elimination rate cannot be explained by alterations in NAD ion or NADH levels. We have also shown that castration of mature rats results in a 70% increase in enzyme activity. This is consistent with the increase in alcohol metabolism observed previously for castrated animals. Since the alcohol metabolic rate appears to be regulated by the content of alcohol dehydrogenase in these physiologic states, we propose to isolate the enzyme forms under these conditions and examine their steady state kinetic properties and their synthesis and degradation rates. These studies should provide a biochemical basis of understanding for the regulation of alcohol metabolism in various nutritional and physiologic states.