Delineation of an in vivo inhibitor for Aspergillus glutamate dehydrogenase
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Title |
Delineation of an in vivo inhibitor for Aspergillus glutamate dehydrogenase
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Creator |
CHOUDHURY, R
NOOR, S VARADARAJALU, LP PUNEKAR, NS |
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Subject |
saccharomyces-cerevisiae
competitive-inhibition molecular-interactions nidulans acid purification niger synthetase metabolism synthase glutamate dehydrogenase isophthalate dimethylisophthalate in vivo inhibition cross-over analysis nitrogen metabolism aspergillus |
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Description |
NADP-glutamate dehydrogenase (NADP-GDH) along with glutamine synthetase plays a pivotal role in ammonium assimilation. Specific inhibitors were valuable in defining the importance of glutamine synthetase in nitrogen metabolism. Selective in vivo inhibition of NADP-GDH has so far been an elusive desideratum. Isophthalate, a potent in vitro inhibitor of Aspergillus niger NADP-GDH [Noor S, Punekar NS. Allosteric NADP-glutamate dehydrogenase from aspergilli: purification, characterization and implications for metabolic regulation at the carbon-nitrogen interface. Microbiology 2005;151:1409-19], was evaluated for its efficacy in vivo. Dimethyl ester of isophthalate (DMIP), but not isophthalate, inhibited A. niger growth on agar as well as in liquid culture. This was ascribed to the inability of isophthalate to enter fungal mycelia. Subsequent to DMIP addition however, intracellular isophthalate could be demonstrated. Apart from NAD-GDH, no other enzyme including NAD-glutamate synthase was inhibited by isophthalate. A cross-over at NADP-GDH step of metabolism was observed as a direct consequence of isophthalate (formed in vivo from DMIP) inhibiting this enzyme. Addition of ammonium to DMEP-treated A. niger mycelia resulted in intensive vacuolation, retraction of cytoplasm and autolysis. Taken together, these results implicate glutamate dehydrogenase and NADP-GDH in particular, as a key target of in vivo isophthalate inhibition during ammonium assimilation. (C) 2007
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Publisher |
ELSEVIER SCIENCE INC
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Date |
2011-07-27T08:00:51Z
2011-12-26T12:56:23Z 2011-12-27T05:45:04Z 2011-07-27T08:00:51Z 2011-12-26T12:56:23Z 2011-12-27T05:45:04Z 2008 |
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Type |
Article
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Identifier |
ENZYME AND MICROBIAL TECHNOLOGY, 42(2), 151-159
0141-0229 http://dx.doi.org/10.1016/j.enzmictec.2007.08.011 http://dspace.library.iitb.ac.in/xmlui/handle/10054/7164 http://hdl.handle.net/10054/7164 |
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Language |
en
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