Competitive inhibition of glutamate dehydrogenase reaction |
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Authors: | Choudhury Rajarshi Punekar Narayan S |
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Institution: | Biotechnology Group, SBB, Indian Institute of Technology, Powai, Mumbai, India. |
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Abstract: | Irrespective of their pyridine nucleotide specificity, all glutamate dehydrogenases share a common chemical mechanism that involves an enzyme bound 'iminoglutarate' intermediate. Three compounds, structurally related to this intermediate, were tested for the inhibition of purified NADP-glutamate dehydrogenases from two Aspergilli, as also the bovine liver NAD(P)-glutamate dehydrogenase. 2-Methyleneglutarate, closely resembling iminoglutarate, was a potent competitive inhibitor of the glutamate dehydrogenase reaction. This is the first report of a non-aromatic structure with a better glutamate dehydrogenase inhibitory potency than aryl carboxylic acids such as isophthalate. A suitably located 2-methylene group to mimic the iminium ion could be exploited to design inhibitors of other amino acid dehydrogenases. |
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Keywords: | Glutamate dehydrogenase 2-Methyleneglutarate Methacrylate Competitive inhibitors |
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