The Participation of Ornithine and Citrulline in the Regulation of Arginine Metabolism in Saccharomyces cerevisiae

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Abstract
The pools of arginine, ornithine and citrulline have been measured under different conditions of growth in wild type and argR mutants (non‐repressible for ornithine transcarbamylase and four other enzymes of the arginine biosynthetic pathway). Comparing these pools with the level of ornithine transcarbamylase and the rate of growth one may conclude: The arginine pool of a wild type strain growing on ammonium as nitrogen source is 18 mM; it increases to 72 mM by addition of arginine to the medium and causes 95% repression of ornithine transcarbamylase synthesis. In decreasing the pool to 3.7 mM by a bradytrophic mutation the differential rate of ornithine transcarbamylase synthesis increases 6 times. When the pool of ornithine is increased by external addition of this amino acid or by using ornithine as the only nitrogen source a repression occurs which reaches 50 to 70% simulataneously with an intense reduction of the arginine pool (≤ 1.2 mM). This low pool may reach a growth limiting value. This shows the existence of a double control by arginine and ornithine. Lysine mimics ornithine. The primary effect of argR mutation is not at the level of the arginine pool. A double regulatory mutant, argR and cpaO (which confers non‐respressibility to carbamoyl‐phosphate synthetase) shows that the double control of arginine and ornithine also reaches this enzyme. The strain bearing simultaneously the argR and cpaO mutations shows an intense distrurbance of metabolism leading to cessation of macromolecules biosyntheses and a loss of viability when basic amino acids such as lysine, ornithine, α‐γ‐diamino butyric acid or arginine are added to a culture growing on glutamate as nitrogen source. Citrulline is shown to be used as nitrogen source via arginine, under these conditions the arginine pool increases to 190 mM, but does not produce the expected high repression. Citrulline or a derivative attenine repression.