Reaction: L-glutamate + H2O + NAD+ = 2-oxoglutarate + NH3 + NADH + H+(overall reaction)
(1a) L-glutamate + NAD+ = 2-iminoglutarate + NADH + H+
(1b) 2-iminoglutarate + H2O = 2-oxoglutarate + NH3
Other name(s): glutamic dehydrogenase; glutamate dehydrogenase (NAD); glutamate oxidoreductase; glutamic acid dehydrogenase; L-glutamate dehydrogenase; NAD-dependent glutamate dehydrogenase; NAD-dependent glutamic dehydrogenase; NAD-glutamate dehydrogenase; NAD-linked glutamate dehydrogenase; NAD-linked glutamic dehydrogenase; NAD-specific glutamic dehydrogenase; NAD-specific glutamate dehydrogenase; NAD:glutamate oxidoreductase; NADH-linked glutamate dehydrogenase
Systematic name: L-glutamate:NAD+ oxidoreductase (deaminating)
Comments: The enzyme is generally involved in the degradation of glutamate into 2-oxoglutarate and ammonia and plays an important role in the interconversion of nitrogen and carbon metabolism. The reaction starts by oxidation of glutamate to 2-iminoglutarate by NAD+, followed by hydrolysis of the latter to 2-oxoglutarate and ammonia. A related NADP-dependent enzyme (EC 1.4.1.4, glutamate dehydrogenase (NADP+)) catalyses the reaction in the opposite direction and plays a role in ammonia anabolism. Some enzymes show dual co-substrate specificity (EC 1.4.1.3, glutamate dehydrogenase [NAD(P)+]).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9001-46-1
References:
1. Nisman, B. The Stickland reaction. Bacteriol. Rev. 18 (1954) 16-42. [PMID: 13140081]
2. Pahlich, E. and Joy, K.W. Glutamate dehydrogenase from pea roots: purification and properties of the enzyme. Can. J. Biochem. 49 (1971) 127-138. [PMID: 4324282]
3. Hochreiter, M.C., Patek, D.R. and Schellenberg, K.A. Catalysis of α-iminoglutarate formation from α-ketoglutarate and ammonia by bovine glutamate dehydrogenase. J. Biol. Chem. 247 (1972) 6271-6276. [PMID: 4346809]
4. Smith, E.L., Austen, B.M., Blumenthal, K.M. and Nyc, J.F. Glutamate dehydrogenases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 11, Academic Press, New York, 1975, pp. 293-367.
5. Fisher, H.F. and Viswanathan, T.S. Carbonyl oxygen exchange evidence of imine formation in the glutamate dehydrogenase reaction and identification of the "occult role" of NADPH. Proc. Natl. Acad. Sci. USA 81 (1984) 2747-2751. [PMID: 6144102]
6. Srinivasan, R., Viswanathan, T.S. and Fisher, H.F. Mechanism of formation of bound α-iminoglutarate from α-ketoglutarate in the glutamate dehydrogenase reaction. A chemical basis for ammonia recognition. J. Biol. Chem. 263 (1988) 2304-2308. [PMID: 3339011]