Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The steady residual activity of ox liver glutamate dehydrogenase at equilibrium with the reversible inactivator pyridoxal 5'-phosphate was measured in the presence and absence of various protecting agents. 2. NAD(+) (up to 15mm) and its 3-acetylpyridine analogue (up to 5mm) both failed to protect, in contrast with NADH. 3. Partial protection was given by glutarate and by succinate. Adipate and pentanoate were much less effective. 4. Correspondingly, whereas succinate and glutarate were both shown to be strong inhibitors of the catalytic reaction, competitive with glutamate, adipate was only weakly competitive, and the still weaker inhibition by pentanoate was non-competitive. 5. When the enzyme was saturated with glutarate, NAD(+) became a good, although still partial, protecting agent. In the absence of protection, 1.8mm-pyridoxal 5'-phosphate decreased enzyme activity to 9%, in the presence of 150mm-glutarate to 29%, and with glutarate and 1mm-NAD(+) only to 73%. 6. 2-Oxoglutarate also promoted protection by NAD(+), but neither pentanoate nor succinate did so. The finding with succinate is remarkable in view of findings 3 and 4 above. 7. It seems possible that substrates or analogues possessing the glutarate structure promote a conformational change that alters the mode of NAD(+) binding. This may explain why glutamate is a much better substrate than norvaline or aspartate and why negative interactions in coenzyme binding occur only in the formation of ternary complexes with glutamate or its analogues.
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PMID:Protection of glutamate dehydrogenase by nicotinamide-adenine dinucleotide against reversible inactivation by pyridoxal 5'-phosphate as a sensitive indicator of conformational change induced by substrates and substrate analogues. 437 49

A variety of metabolites have been found to elicit a form of inhibition or activation on an NAD-specific glutamate dehydrogenase (NAD-GDH, EC 1.4.1.2) from Halobacterium halobium. The purified halophilic enzyme was tested with several compounds known to be allosteric modifiers of mammalian glutamate dehydrogenases to determine their effects on enzyme activity. GTP, ATP, ADP and AMP did not affect the enzyme, so these effectors of bovine glutamate dehydrogenase do not play a role in the regulation of the halophilic enzyme. However, the halophilic enzyme was subject to strong inhibition by TCA intermediates. When measuring the initial rate of the reaction, the oxidative deamination of L-glutamate was inhibited by TCA metabolites such as: fumarate, oxalacetate, succinate and malate; by substrate analogues such as: NADP+, D-glutamate and glutarate; and by dicarboxylic compounds such as adipate. On the other hand, all the amino acids tested were activators of this enzyme, except the D-isomer of the substrate L-glutamate that acted as an inhibitor. The relative effectiveness of each inhibitor or activator (Ki or Ka values) was correlated with the dipole moment (mu), HOMO and LUMO molecular orbital energies, optimal distance between two carboxyl groups, and hydrophobicity. Compounds with high dipole moment acted as good activators while compounds with low dipole moment were inhibitors. We have also found that the best activators were amino acids with no polar lateral chain.
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PMID:NAD-glutamate dehydrogenase from Halobacterium halobium: inhibition and activation by TCA intermediates and amino acids. 860 24