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A novel mammalian glucokinase exhibiting exclusive inorganic polyphosphate dependence in the cell nucleus

Ali, Antasar, Wathes, D. Claire, Swali, Angelina, Burns, Helena and Burns, Shamus P. (2017) A novel mammalian glucokinase exhibiting exclusive inorganic polyphosphate dependence in the cell nucleus. Biochemistry and Biophysics Reports, 12. pp. 151-157. ISSN 2405-5808

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Background: Hexokinase and glucokinase enzymes are ubiquitously expressed and use ATP and ADP as substrates in mammalian systems and a variety of polyphosphate substrates and/or ATP in some eukaryotic and microbial systems. Polyphosphate synthesising or utilizing enzymes are widely expressed in microbial systems
but have not been reported in mammalian systems, despite the presence of polyphosphate in mammalian cells.
Only two micro-organisms have previously been shown to express an enzyme that uses polyphosphate exclusively.
Methods: A variety of experimental approaches, including NMR and NAD-linked assay systems were used to conduct a biochemical investigation of polyphosphate dependent glucokinase activity in mammalian tissues.
Results: A novel mammalian glucokinase, highly responsive to hexametaphosphate (HMP) but not ATP or ADP as a phosphoryl donor is present in the nuclei of mammalian hepatocytes. The liver enzyme exhibited sigmoidal kinetics with respect to glucose with a S0.5 of 12 mM, similar to the known kinetics of mammalian ATP-glucokinase. The Km for HMP (0.5 mM) was also similar to that of phosphoryl donors for mammalian ATP-glucokinases. The new enzyme was inhibited by several nucleotide phosphates.
Conclusions: We report the discovery of a polyphosphate-dependent enzyme system in mammalian cells with kinetics similar to established ATP-dependent glucokinase, also known to have a nuclear location. The kinetics
suggest possible regulatory or redox protective roles.
General significance: The role of polyphosphate in mammalian systems has remained an enigma for decades, and the present report describes progress on the significance of this compound in intracellular metabolism in

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
Related URLs:
Depositing User: Shamus Burns
Date Deposited: 31 Oct 2017 14:10
Last Modified: 28 Aug 2021 15:28


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