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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; Burns, Shamus

Authors

Antasar Ali

D. Claire Wathes

Helena Burns

Shamus Burns



Abstract

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 mammals.

Citation

Ali, A., Wathes, D. C., Swali, A., Burns, H., & Burns, S. (2017). A novel mammalian glucokinase exhibiting exclusive inorganic polyphosphate dependence in the cell nucleus. Biochemistry and Biophysics Reports, 12, https://doi.org/10.1016/j.bbrep.2017.09.004

Journal Article Type Article
Acceptance Date Sep 15, 2017
Online Publication Date Sep 20, 2017
Publication Date Dec 1, 2017
Deposit Date Oct 25, 2017
Publicly Available Date Mar 29, 2024
Journal Biochemistry and Biophysics Reports
Electronic ISSN 2405-5808
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 12
DOI https://doi.org/10.1016/j.bbrep.2017.09.004
Keywords Glucokinase ; Hexokinase ; Polyphosphate ; Evolution
Public URL https://nottingham-repository.worktribe.com/output/897716
Publisher URL http://www.sciencedirect.com/science/article/pii/S2405580817301929?via%3Dihub

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