Delineation of an in vivo inhibitor for Aspergillus glutamate dehydrogenase

Enzyme and Microbial Technology
Rajarshi ChoudhuryNarayan S Punekar

Abstract

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 DMIP-treated A. niger mycelia resulted in intensi...Continue Reading

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Citations

Sep 22, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sunil KumarNarayan S Punekar
Apr 20, 2010·Molecular and Biochemical Parasitology·Isabela M AparicioPaul C Engel
Nov 20, 2014·Amino Acids·Kamila Jastrzębowska, Iwona Gabriel
Nov 6, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Prem PrakashPrasenjit Bhaumik
Jun 7, 2015·Applied and Environmental Microbiology·Sunil KumarNarayan S Punekar
Oct 12, 2019·PloS One·Baljinder Kaur, Narayan S Punekar
Mar 16, 2018·The Journal of Biological Chemistry·Prem PrakashPrasenjit Bhaumik
Oct 24, 2018·Frontiers in Microbiology·Cindy VallièresSimon V Avery
Sep 17, 2021·Environmental Microbiology·Venkatesh M Ghodke, Narayan S Punekar
Nov 9, 2021·Proteins·Barsa Kanchan Jyotshna GodsoraPrasenjit Bhaumik

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