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Possible Interactions between the Urea Cycle and Synthesis of Pyrimidines and Polyamines in Regenerating Liver¹

Division of Biological and Medical Sciences, Brown University, Providence, Rhode Island 02912 [N.F., J.T.B.]; and Department of Biochemistry, Downstate Medical Center, State University of New York, Brooklyn, New York 11203 [L.K.]

Ornithine levels rise progressively in the liver of partially hepatectomized rats, probably as a consequence of the increased flow of metabolites through the urea cycle. Ammonia and urea concentrations in the blood and liver of partially hepatectomized animals are not significantly different from those of sham-operated rats. However, in regenerating livers, the ability to remove ammonia from the blood is close to its maximal limit. Ammonia overload leads to the production of large amounts of orotic acid and causes a marked elevation of hepatic ornithine decarboxylase activity. Among the pyrimidine precursors dihydroorotic acid injections increase the activity of the enzyme while orotic acid is without effect. A peak of labeled material that corresponds to dihydroorotic acid was identified by partition chromatography of acid-soluble extracts of livers of partially hepatectomized rats previously given injections of [¹⁴C]bicarbonate. The labeling of dihydroorotic acid from [¹⁴C]bicarbonate is increased in the liver of rats given injections of ornithine. Despite the difficulties involved in studies of ornithine decarboxylase activity in vivo, our results suggest that mutual interactions between urea, pyrimidine, and polyamine synthesis take place during liver regeneration.

¹ Supported by Grant AM14706 from the NIH.

Received 9/ 3/74. Accepted 10/25/74.

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