THE REGULATION OF HEPATIC ENZYME ACTIVITY BY ADENOSINE TRIPHOSPHATE (ATP).

Abstract

Abstract Ethionine has been found to produce a rapid fall in the level of ATP in the liver of female rats. The decrease in ATP concentration has at least two consequences upon the hepatic enzymic spectrum, namely, the accumulation of inactive phosphorylase due to diminished reactivation of the enzyme and an inhibition of protein synthesis. The male also shows a decrease in ATP concentration following ethionine administration but of a lesser magnitude than the female. The difference in the levels of ATP between the two sexes appears to be sufficient to account for the observed sex difference in the decrease in the activity of hepatic phosphorylase and in protein synthesis induced by ethionine. Despite the decrease in ATP concentration in the female, sufficient ATP is made available for the con version of a considerable amount of free fatty acid to triglyceride in the liver. These data are consistent with the existence of a priority system for ATP utilization in the liver cell whereby certain reactions may continue uninhibited even when the levels of ATP drop to very low levels. The results of the present study indicate that, at least under some pathologic circumstances, the tissue level of ATP may be an important determinant of enzymatic activity in the liver.