Tungstate: a potent inhibitor of multifunctional glucose-6-phosphatase

Archives of Biochemistry and Biophysics
J D FosterR C Nordlie

Abstract

The insulin-like action of tungstate in diabetic rats (A. Barberà et al., 1994, J. Biol. Chem. 269, 20047-20053) prompted us to examine the effects of tungstate on the glucose-6-phosphatase system. Our results indicate that tungstate is a potent inhibitor of glucose-6-phosphatase, with a Ki in the 10-25 microM range determined with native microsomes and in the 1-7 microM range determined with detergent-treated microsomes. With both preparations, simple linear competitive inhibition was observed versus glucose 6-phosphate (glucose-6-P) as substrate with the glucose-6-P phosphohydrolase activity of the enzyme. Tungstate was a simple linear competitive inhibitor versus carbamyl phosphate (carbamyl-P) and a linear noncompetitive inhibitor versus glucose with the carbamyl-P:glucose phosphotransferase activity of the glucose-6-phosphatase system. These findings, in addition to the observation that tungstate protected the enzyme against thermal inactivation, indicate that tungstate binds with high affinity and competes at the active site of the enzyme where the substrates glucose-6-P and carbamyl-P bind prior to catalysis. Our results suggest that potent inhibition of glucose-6-P hydrolysis by tungstate is likely responsible, at least...Continue Reading

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Citations

Mar 7, 2002·The Biochemical Journal·Emile van Schaftingen, Isabelle Gerin
Apr 28, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·David R JohnsonLaura S Inouye
Apr 17, 2013·FEBS Letters·C J Rodriguez-HernandezJ J Guinovart
Feb 24, 2007·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Milena Jelikić-StankovPredrag Djurdjević
Feb 13, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Alicia M BoltKoren K Mann
May 11, 2007·Biochemical and Biophysical Research Communications·Sandra PiquerRamon Gomis
Feb 11, 2016·The Journal of Endocrinology·Zengmin WangKenneth McCormick
Jun 3, 2014·Metallomics : Integrated Biometal Science·Zaitoon IlyasJamshed Iqbal
Aug 20, 2003·The Journal of Biological Chemistry·Jorge E DomínguezJoan J Guinovart
Aug 23, 2018·Journal of Cellular Physiology·Romina BertinatFrancisco Nualart
Aug 1, 2009·Biological Trace Element Research·Aleksandra TopicDragana Vucicevic
Feb 25, 2010·Journal of Immunotoxicology·Andrew R OsterburgGeorge F Babcock
Jan 15, 2004·The Journal of Biological Chemistry·Anthony J PetrolonisSuk-Bong Hong
Jul 30, 2021·Toxicology Mechanisms and Methods·Sherry Sachdeva, Wolfgang Maret

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