Imbalance in ornithine metabolism in hepatomas of different growth rates as expressed in behavior of L-ornithine carbamyl transferase activity.

The behavior of ornithine carbamyl transferase activity (carbamylphosphate :1.-ornithine carbamyltransferase, EC 2.1 .3.3) was compared in proliferating normal liver (from developing rats and from partially hepatectomized rats) and in neoplastic liver (spectrum of hepatomas of different growth rates). The behavior of the liver enzyme in starved animals was also examined. The enzyme activity was determined in the homogenate. The affinity of the liver enzyme to ornithine was Km 1.0 mM , for carbamyl phosphate it was Km 0.8 mM, and an optimum pH of 9.0 was observed. In the hepatomas the affinity of the enzyme and the pH optimum were similar to the values of the liver of control normal rats. Six-day starvation decreased the liver enzyme activity in the average cell to 40% of the activity of fed rats. Studies in differentiation showed that the enzyme activity of the average hepatic cell in the newborn rat was 33% of that of the adult, and it increased gradually during development. In a spectrum of hepatomas omithine carbamyl transferase activity decreased in parallel with the increase in hepatoma growth rate. In the most rapidly growing tumors (3924A, 3683F) the activities were less than 1% of those observed in the liver of control rats of the same strain, sex, age, and weight. In the regenerating liver at 24 hr after partial hepatectomy, the enzyme activity decreased to 83% of that of the sham-operated controls. Since the regenerating liver proliferates at a rate comparable to that of the rapidly growing hepatoma, the marked decrease observed in the tumor appears to be specific to neoplastic cell growth. The close linking of the decrease in the activity of this enzyme with the increase in hepatoma growth rate provides further evidence in support of the Molecular Correlation Concept. The decrease in the activity of omithine carbamyl