Selective induction and suppression of liver enzyme synthesis

Abstract

Two techniques were used to demonstrate selective induction of enzyme increases in mammalian tissue in vivo: a) refeeding of fasted animals, and b) administration of cortisone to adrenalectomized animals. Refeeding acted selectively as an inducer for the stimulation of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities, and as a less effective inducer of phosphoglucomutase, phosphohexose isomerase, glucose-6-phosphatase, and lactic dehydrogenase. On the other hand, cortisone acted selectively as an inducer for increases in glucose-6-phosphatase, fructose-1, 6-diphosphatase, phosphohexose isomerase and lactic dehydrogenase, and as a less effective inducer of 6-phosphogluconate dehydrogenase. Thus, refeeding primarily stimulated enzymes mediating the direct oxidation of glucose-6-phosphate, whereas cortisone stimulated enzymes involved in gluconeogenesis. The amino acid analogue ethionine selectively inhibited the induced increase of enzyme activities and methionine reversed the ethionine inhibition. The nature of the elevations in the enzyme activities and the mechanisms of ethionine inhibition were discussed.