Genetic influence upon phenobarbital-induced increase in rat liver supernatant aldehyde dehydrogenase activity.

Treatment with phenobarbital of rats which are genetically selected results in a greater than IO-fold increase in nicotinamide-adenine dinucleotide (NAD)-dependent aldehyde dehydrogenase present in the supernatant but not the mitochondrial fraction of liver. This effect represents one of only a few known cases where intrastrain differences in a drug-induced increase in enzyme activity is genetically controlled. The kinetic characteristics of the enzyme from phenobarbital-treated rats are the same, regardless of whether or not the enzyme activity in the liver is increased. It is also demonstrated that rat liver supernatant contains a second NAD-dependent aldehyde dehydrogenase which (a) is resistant to induction by phenobarbital; (b) oxidizes fi-carboxybenzaldehyde; (c) is relatively uninhibited by disulfirarn; (d) has a heat stability different from the inducible enzyme.