Genetic control of serine dehydratase and phosphoenolpyruvate carboxykinase in mice

Inbred strains of mice were found to differ with regard to their endogenous activities of the liver enzyme serine dehydratase (SD) and phosphoenolpyruvate carboxykinase (PEPCK). The strain distribution patterns for the activity of each enzyme were identical. On feeding of high-protein diets or on fasting, the activities of both enzymes were induced in a concordant fashion which suggested the control of both enzymes by a single gene. Genetic analysis established that the induction of both enzymes on feeding of high-protein diets was controlled by a single gene (Sdr-1), whereas the induction of SD, but not of PEPCK, in fasting was controlled by different single gene (Sdr-2). The lack of segregation of the backcross generations with respect to PEPCK activities obtained on fasting precluded the establishment of any association of the response of PEPCK to fasting with either the Sdr-1 or Sdr-2 locus. The strain of mice (BALB/cJ) that had the ability to maximally induce both gluconeogenic enzymes under both dietary treatments failed to survive a fast as long as those strains with less ability to induce. This suggests that the ability to induce key enzymes in gluconeogenesis when food is unavailable is of little consequence with regard to their ability to produce essential nutrients necessary for survival.