THE EFFECT OF CERTAIN COMPOUNDS ON THE IN VITRO SYNTHESIS OF UREA AND ITS PRECURSORS

¹ Department of Physiology and Pharmacology, Duke University School of Medicine, Durham, North Carolina

1. In concentrations of 1 x 10^-3 M, methyl-bis-(beta-chloroethyl)-amine·HCl (MBA) and podophyllotoxin (PPX) inhibit urea synthesis in vitro by depressing the formation of carbamylglutamate, but not the combination of the latter with ornithine. In addition this concentration of PPX weakly inhibits the hydrolysis of arginine, but an equimolar amount of MBA does not affect arginase.

2. The same concentration of colchicine depresses urea formation by a slight inhibition of arginase. However, a ten-fold increase in the amount of colchicine also inhibits the formation of carbamylglutamate.

3. In these concentrations urethane does not inhibit urea synthesis under any condition tested.

4. Studies with various concentrations of inhibitors indicate that the degree of inhibition is proportional to the negative logarithm of the final molar drug concentration.

5. The d-isomer of ornithine apparently inhibits urea synthesis by competing with l-ornithine for the enzyme system.