Arginase activity during the growth cycle of Chang's liver cells.

An increase of arginase activity has been produced in Chang’s liver cells in suspension cultures by increasing the concentration in the growth medium of lysine, leucine, valine, or ornithine. These amino acids are known to inhibit enzymes in the arginase-initiated reaction sequence from arginine to proline. An increase in arginase also occurred with o-aminobenzaldehyde, a compound which reacts with a metabolite (Al-pyrroline 5-carboxylate) of the same reaction chain. A stimulation of arginase has been also shown following substitution of citrulline for arginine in the growth medium. A decrease in arginase was found after addition of proline, a product of the same reaction sequence. Experiments in which protein synthesis was inhibited by puromycin indicate that the rate of accumulation of enzyme protein was involved rather than an activation or inactivation of preformed enzyme. When arginase was stabilized by the addition of manganese to the growth medium, the compounds mentioned above produced the same results as before, although greater in magnitude, indicating an effect on the rate of synthesis rather than on the rate of degradation of the enzyme during general protein turnover. These results suggest that synthesis of arginase in Chang’s liver cells during a normal 4-day growth cycle is regulated, in part at least, by product repression.