DEMONSTRATION OF ARGININOSUCCINATE SYNTHETASE-ACTIVITY ASSOCIATED WITH MITOCHONDRIAL-MEMBRANE - CHARACTERIZATION AND HORMONAL-REGULATION

Argininosuccinate synthetase (AS) is the third enzyme in ureogenesis, it catalyses the reaction of condensation of citrulline and aspartate into argininosuccinate. In the present report, we described the first characterization of AS within the outer membrane of rat liver mitochon dria. Mitochondria-associated AS displayed the same kinetic characteri stics as the cytoplasmic enzyme, but was found to be thermostable whil e cytoplasmic AS was not. The evolution of the co-location of AS was a nalyzed during ontogenesis. Total AS activity increased throughout rat fetal development. Simultaneously, the subcellular distribution of th e enzyme has changed. AS activity was mainly mitochondrial in fetal an d new-born liver liver and cytoplasmic in adult rat liver. The variati on in subcellular distribution of AS may be due to the dramatic change s in hormonal levels that occur during this period. The role of cortic osteroid and pancreatic hormones was studied. During fetal period, cor ticosteroid hormones induced an increase in mitochondria-associated AS activity. This was prevented by insulin. Glucagon did not modify tota l AS activity but reduced mitochondrial AS activity, meanwhile, a comp arable increase in cytoplasmic AS activity was observed. One may hypot hesize that glucagon may participate in the transfer of mitochondrial enzyme into the cytosol.