Changes in the activities of urea-cycle enzymes after the administration of carbon tetrachloride

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Abstract
The activities of the urea-cycle enzymes in rat liver have been studied at different times after the administration of carbon tetrachloride, measurements being made l[center dot]5, 3, 6 and 24 hr. after a single dose of the drug was given by stomach tube as well as 2 and 4 days after daily subcutaneous injections of carbon tetrachloride. At 1[center dot]5 hr. after treatment there was an increase in the two mitochondria-linked enzymes, carbamoyl phosphate synthetase and ornithine trans-carbamoylase, both as units/g. of liver and as total activity. The activities of these enzymes were further increased at 3 and 6 hr. At these times the activities of the enzymes of the urea cycle located in the soluble fraction of the cell, the arginine-synthetase system, arglnlnosuc-cinase and arginase, were unchanged. At 24 hr. after treatment the activities of both carbamoyl phosphate synthetase and ornithine trans-carbamoylase fell, both in relation to the elevated values at 6 hr. and, for the former enzyme, in relation to the control values. The total activity of the arginine-synthetase system decreased. Treatment with carbon tetrachloride for 4 days led to a marked decrease in the activities of all the enzymes of the urea cycle with the exception of arglninosucci-nase. There were no significant changes in the activities of carbamoyl phosphate synthetase and ornithine transcarbamoylase in livers from adrenalectomized rats 3 hr. after treatment with carbon tetrachloride. Corticosterone acetate and hydrocortisone injections produce no short-term changes (at 3 and 1[center dot]5 hr. respectively) in the activities of these enzymes in normal rat liver. The effects of Ca2+ions in vitro on the activities of all five enzymes of the urea cycle have been measured, as well as the concentration of Ca2+ion in the livers of treated animals; the pattern of change in the activities of urea-cycle enzymes after carbon tetrachloride poisoning are considered in relation to these effects.