Molecular Pharmacology, Vol 10, 41-47, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Ornthine Decarboxylase Turnover Slowed by -Hydrazinoornithine

¹ Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

-Hydrazino-ornithine is a potent and selective inhibitor of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17). When added to rat hepatoma cells at the time of dilution, -hydrazino-ornithine elicits a dose-related increase in ornithine decarboxylase activity and a concomitant prolongation of the apparent half-life of the enzyme from 10 min to 28 min, as determined by the rate of decline of ornithine decarboxylase activity after inhibition of protein synthesis by cycloheximide. Similarly, systemic administration of -hydrazinoornithine to nephrectomized rats induces a dose-related enhancement of ornithine decarboxylase activity in the normal and regenerating liver, which is associated with prolongation of the apparent half-life of the enzyme. In both intact liver and hepatoma cells in culture, the decrease in the turnover rate of the enzyme can account for its increased activity.

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ACKNOWLEDGMENTS The technical assistance of Donald P. Kramer and Lydia Hernaez is gratefully acknowledged.