Molecular Pharmacology, Vol 4, 173-180, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Increased Activity of Enzymes for de Novo Pyrimidine Biosynthesis after Orotic Acid Administration

¹ Department of Pharmacology, Baylor University College of Medicine, Houston, Texas 77025

Administration of a purified diet supplemented with 1% orotic acid is attended by a marked elevation in the specific activities of liver aspartate transcarbamylase (ATC), ornithine transcarbamylase, and dihydroorotase (DHOase) and in alterations in the composition of the acid-soluble nucleotide pool. Return of the rats to the control diet is followed by an immediate reinstatement of the normal acid-soluble nucleotide composition and by a slower return of the enzyme activities to basal values. The half-life of the return has been calculated as 2.5 and 0.5 days, for ATC and DHOase, respectively. Both ATC and DHOase activities are augmented in regenerating liver derived from rats fed either control or orotic acid diet. The studies suggest that high intracellular concentrations of pyrimidine nucleotides may not "repress" the enzymes involved in the de novo synthesis of pyrimidines in mammalian liver.

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ACKNOWLEDGMENTS This work was supported by a grant from the United States Public Health Service, CA06571, and by an institutional grant from the American Cancer Society, ACS IN 27 H No. 11.