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 mitochondria. Mitochondria-associated AS displayed the same kinetic characteristics as the cytoplasmic enzyme, but was found to be thermostable while cytoplasmic AS was not. The evolution of the co-location of AS was analyzed during ontogenesis. Total AS activity increased throughout rat fetal development. Simultaneously, the subcellular distribution of the enzyme has changed. AS activity was mainly mitochondrial in fetal and new-born liver liver and cytoplasmic in adult rat liver. The variation in subcellular distribution of AS may be due to the dramatic changes in hormonal levels that occur during this period. The role of corticosteroid and pancreatic hormones was studied. During fetal period, corticosteroid hormones induced an increase in mitochondria-associated AS activity. This was prevented by insulin. Glucagon did not modify total AS activity but reduced mitochondrial AS activity, meanwhile, a comparable increase in cytoplasmic AS activity was observed. One may hypothesize that glucagon may participate in the transfer of mitochondrial enzyme into the cytosol.
Laboratoire d'Endocrinologie, Université de Haute Normandie, Faculté des Sciences, Mont Saint Aignan, France.
J
J
Demarquoy
A
A
Fairand
C
C
Gautier
R
R
Vaillant
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001124:Argininosuccinate Synthase / Q000378:metabolism*; D005591:Chemical Fractionation; D003600:Cytosol / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D004795:Enzyme Stability; D005260:Female; D007425:Intracellular Membranes / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000648:ultrastructure; D010187:Pancreatic Hormones / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000305:Adrenal Cortex Hormones; D010187:Pancreatic Hormones; D001124:Argininosuccinate Synthase