Effects of Casein Hydrolysate on the Induction and Regulation of Tyrosine-α-Ketoglutarate Transaminase in Rat Liver

Abstract

A several fold increase in the activity of tyrosine-α-ketoglutarate transaminase occurs in intact or adrenalectomized rats following treatment with an enzymatic hydrolysate of casein, whereas tryptophan pyrrolase is unresponsive to this treatment. Doses of tyrosine, tryptophan, or the combination of these amino acids equivalent in amount to those contained in an effective dose of casein hydrolysate did not produce a rise in tyrosine transaminase activity. The effect of casein hydrolysate is inhibited by actinomycin D or cycloheximide, indicating that the synthesis of new RNA and protein is associated with the response of tyrosine transaminase to casein hydrolysate. Additive and, in some cases, synergistic effects on tyrosine transaminase are observed when casein hydrolysate and hydrocortisone are given together or sequentially. In contrast to the response of this enzyme, no additive effect on tryptophan pyrrolase or serine dehydrase occurs when 1 g of casein hydrolysate is given at the same time as a large dose of hydrocortisone. Treatment of adrenalectomized rats with casein hydrolysate, 4 or 8 hours after they were treated with hydrocortisone, stimulates a marked further increase in the activity of tyrosine transaminase. In intact rats, tyrosine transaminase shows a synergistic response to casein hydrolysate when it is given concomitantly with a small dose of hydrocortisone; under these conditions tryptophan pyrrolase is also responsive, but this effect appears to be due to tryptophan stabilization of the enzyme against degradation. When a low dosage of hydrocortisone is administered to intact rats, tryptophan pyrrolase, but not tyrosine transaminase, shows an increase in activity. On the other hand, of these two enzymes, only the transaminase responds to casein hydrolysate. Each of these treatments stimulates the incorporation of orotic acid-6-14C into liver RNA to about the same extent, indicating either that this is a selective effect or that factors in addition to new RNA synthesis are involved in the induction of these enzymes.