Abstract
Hepatic tryptophan pyrrolase decreased rapidly its activity within 6 hours after administration of CCl4 (0.05 ml-0.25 ml/kg, p.o.) to rats and fell to 30-40 96 of the basal level of the control in 24 hours. On the contrary, tyrosine transaminase increased its hepatic level by several times over the basal activity in 6 to 10 hours and returned to the basal level in 24 hours after poisoning. The mechanisms concerned with such an inverse change in activity were studied.
I. Inhibition of Tryptophan Pyrrolase Synthesis by CCl4
1) Induction of tryptophan pyrrolase by glucocorticoid together with L-tryptophan was markedly inhibited by CCl4.
2) Decrease in activity and reduction of inducibility of pyrrolase were caused neither by an inhibitor- or an activator-effect, nor by change in Km value for the substrate of the enzyme in the poisoned liver.
3) When degradation rates of pyrrolase in the liver were determined by measuring the rate of decline of the activity after administration of puromycin, no significant enhancement of degradation was observed in intoxicated rats.
4) Actinomycin D-mediated superinduction of pyrrolase was inhibited by concomi- tant administration of CCl4.
5) These results suggest that the possible reason for the diminished functional activity of pyrrolase should be loss of synthetic activity of the enzyme due to defect of translational level in the poisoned liver.
11. Tyrosine Transaminase Induction by Differential Inhibitory Effects of CCl4.
1) Elevation of tyrosine transaminase observed after administration of glucororticoid together with L-tryptophan was lower in the poisoned liver than that in the intact liver, what indicates that the induction of transaminase by hormone was inhibited by CCl4.
2) The results of an immunological analysis carried out in addition to an admixture experiment indicated that increase in basal activity and reduction in capacity of hormone-mediated induction of the enzyme was derived from a net change in immunologically crossreactive transaminase protein.
3) An immunochemical method was employed to study pulse labeling of transaminase and to “chase” the degradation of prelabeled enzyme protein. The results suggested that the rise of transaminase in the intoxicated liver resulted from a marked decrease in the rate of enzyme degradation. Synthesis of the enzyme was also inhibited by CCl4 but relatively slowly.
4) Further rise in transaminase levels was observed following administration of CCl4 either alone or together with actinomycin D to adrenalectomized rats which had been induced by cortisol. By an isotopic-immunochemical analysis, it was elucidated that such a CCl4-mediated superinduction of transaminase was also caused by the differential inhibitory effects of CCl4.
5) These results suggested also that the inhibition of synthesis and of degradation of transaminase by CC14 appeared to occur at the translational level.
