Glutamine Synthetase. I. a Comparative Study of Its Distribution in Animals and Its Inhibition by Dl-allo-delta-hydroxylysine.

A b s t r a c t 1 . The optimal conditions for assaying glutamine synthetase activity in tissue homogenates have been investigated. 2. The distribution of the synthetase activity in seventeen species of the vertebrates and one species of Protozoa (Tetrahymena pyriformis) has been studied. 3. The present study shows that a definite correlation exists between the distribution of glutamine synthetase in animals and the phylogenetic classification. (a) The enzyme activity was found in the brain of all vertebrates examined. From the fishes to the ureotelic reptiles, brain was also the only organ where the enzyme activity could be found. (b) The enzyme activity occurred in the liver of all animals from the uricotelic reptiles to the mammals. (c) The enzyme activity was detectable in the kidney of some mammals, in the heart of the birds, and in the pancreas of the uricotelic animals. I t was present also in the spleen, lung, and testis of some species of animals. (d) The enzyme activity was not observed, however, in the blood, skeletal muscle, skin, or small intestine of any species used. 4. The significance of the synthetic reaction in the detoxication of ammonia and in the maintenance of balance of the glutamic acid-glutamine system is discussed. 5. The glutamine content in the liver of many species of animals was not related to the synthetase activity in either the liver or the brain of these animals. 6. The protozoan possessed the enzyme activity also. 7. DL-Allo-~-hydroxylysine inhibited glutamine synthetase activity in a variety of tissues from many species of animals. The inhibition was noncompetitive with respect to glutamate.