Amino acid induction and carbohydrate repression of dimethylnitrosamine demethylase in rat liver.

Abstract

Starvation of rats for 24 hr considerably enhances hepatic dimethylnitrosamine demethylase activity, and 3-methylcholanthrene pretreatment inhibits the enzyme in starved animals to the same extent as in fed animals. Determination of the kinetic constants following starvation revealed significant increase of the apparent Vmax indicating increase in the amount of demethylase. There was no significant change in the Km. Studies with actinomycin D provide strong support that starvation-induced increase is due to de novo protein synthesis, consistent with the observed increase in maximal velocity. Ingestion of glucose markedly inhibits demethylase activity while ingestion of casein alone stimulates it appreciably, in a manner analogous to such phenomena with a few other hepatic enzymes. These results and previous data suggest that the level of dimethylnitrosamine demethylase in liver is under the control of multiple regulatory factors.