Biomaterial Database

Studies on the mechanism of the glutamine-dependent reaction catalyzed by asparagine synthetase from mouse pancreas. 1980

H A Milman, and D A Cooney, and C Y Huang

Initial velocity and product inhibition studies were conducted with the glutamine-dependent reaction of asparagine synthetase from mouse pancreas. Double reciprocal plots of glutamine versus either aspartate or ATP were parallel, while aspartate versus ATP gave intersecting patterns. These patterns are indicative of a hybrid ping-pong mechanism consisting of a glutaminase partial reaction and a sequential catalysis involving aspartate and ATP. Inhibition patterns of the four products, glutamate, AMP, PPi, and asparagine, versus each of the three substrates are consistent with a hybrid Uni Uni Bi Ter Ping Pong Theorell-Chance mechanism where the glutaminase reaction occurs first and aspartate binds to the enzyme before ATP in the sequential segment. PPi is the first product released in the Theorell-Chance reaction, which is followed by the ordered release of AMP and asparagine. Product inhibition patterns also indicate the formation of E . NH3 . Asn and E . NH3 . Asp . AMP abortive complexes. Although an amide site (for glutamine and asparagine), presumably responsible for the glutaminase reaction, an acid site (for glutamate and aspartate), and a nucleotide site are involved in the overall catalysis, the "two-site" ping-pong mechanism is incompatible with the experimentally observed product inhibition patterns.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008025	Ligases	A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.	Ligase,Synthetases,Synthetase
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D010179	Pancreas	A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D005973	Glutamine	A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.	D-Glutamine,L-Glutamine,D Glutamine,L Glutamine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001217	Aspartate-Ammonia Ligase	An enzyme that catalyzes the formation of asparagine from ammonia and aspartic acid, in the presence of ATP. EC 6.3.1.1.	Asparagine Synthase,Asparagine Synthetase,Asparagine Synthetase B,Aspartate Ammonia Ligase,Ligase, Aspartate-Ammonia,Synthase, Asparagine,Synthetase B, Asparagine,Synthetase, Asparagine
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus