REGULATION OF ARGININOSUCCINATE SYNTHETASE LEVEL BY CORTICOSTEROID AND PANCREATIC HORMONES DURING PERINATAL-PERIOD

The urea cycle takes place in the hepatocyte of ureothelic animals. Th e conversion of ammonia into urea involves five reactions. The first 2 take place in the matrix of the mitochondria, the last 2 occur in the cytosol. Argininosuccinate synthetase (AS) is the third reaction of t he urea cycle. It catalyses the condensation of citrulline and asparta te into arginonosuccinate. We have previously reported that rat AS act ivity was present in the cytosol and the outer membrane of the mitocho ndria. We have shown that, at the activity level, the colocation of AS was changing during fetal and neonatal development and was under the control of corticosteroid and pancreatic hormones. However, an unresol ved issue was whether both AS had the same specific activity and that their location was changing during ontogenesis or that the specific ac tivities of mitochondrial and cytosolic enzymes were different and/or modified during this period. In the present report, we compared the co mpartmentalization of AS activity and protein level in the fetus, the new-born and the adult rat and the role of corticosteroid and pancreat ic hormones. Specific activities of both AS remained unchanged during ontogenesis. Glucocorticoids induced an increase in mitochondrial AS w hile glucagon appeared to induce a concomitant decrease in the level o f mitochondrial AS and an increase in cytosolic AS.