Molecular and Cellular Biochemistry

, Volume 364, Issue 1–2, pp 131–145 | Cite as

Expression and role in glycolysis of human ADP-dependent glucokinase

  • Susan Richter
  • Jan P. Richter
  • Sunali Y. Mehta
  • Amanda M. Gribble
  • Andrew J. Sutherland-Smith
  • Kathryn M. Stowell
  • Cristin G. Print
  • Ron S. Ronimus
  • William R. Wilson


A novel murine enzyme, ADP-dependent glucokinase (ADPGK), has been shown to catalyse glucose phosphorylation using ADP as phosphoryl donor. The ancestral ADPGK gene appears to have been laterally transferred from Archaea early in metazoan evolution, but its biological role has not been established. Here, we undertake an initial investigation of the functional properties of human ADPGK in human tumour cell lines and specifically test the hypothesis that ADPGK might prime glycolysis using ADP under stress conditions such as hypoxia. Recombinant human ADPGK was confirmed to catalyse ADP-dependent glucose phosphorylation in vitro, with an apparent KM for glucose of 0.29 mM. Expression databases and western blotting of surgical samples demonstrated high expression in many human tissues, including tumours. Unlike hexokinase-2 (HK2), RNAi studies with exon arrays showed that ADPGK is not a transcriptional target of hypoxia inducible factor-1. Consistent with this, ADPGK protein was not upregulated by hypoxia or anoxia. Surprisingly, stable fivefold overexpression of ADPGK in H460 or HCT116 cells had no apparent effect on proliferation or glycolysis, and did not rescue clonogenicity or glycolysis when HK2 was suppressed by siRNA. Furthermore, suppression of ADPGK by siRNA did not cause detectable inhibition of glycolysis or cell killing by anoxia, although it did induce a statistically significant decrease in plating efficiency of H460 cells under aerobic conditions. Thus, human ADPGK catalyses ADP-dependent phosphorylation of glucose in vitro, but despite its high expression in human tumour cell lines it appears not to make a quantifiable contribution to glycolysis under the conditions evaluated.


ADP-dependent glucokinase Glycolysis Hypoxia siRNA Hexokinase-2 Exon arrays 

Supplementary material

11010_2011_1212_MOESM1_ESM.pdf (562 kb)
Supplementary material 1 (PDF 562 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Susan Richter
    • 1
  • Jan P. Richter
    • 3
  • Sunali Y. Mehta
    • 2
  • Amanda M. Gribble
    • 3
  • Andrew J. Sutherland-Smith
    • 3
  • Kathryn M. Stowell
    • 3
  • Cristin G. Print
    • 2
  • Ron S. Ronimus
    • 4
  • William R. Wilson
    • 1
  1. 1.Auckland Cancer Society Research CentreFaculty of Medical and Health Sciences, The University of AucklandAucklandNew Zealand
  2. 2.Dept of Molecular Medicine and PathologyFaculty of Medical and Health Sciences, The University of AucklandAucklandNew Zealand
  3. 3.Institute of Molecular BioSciencesMassey UniversityPalmerston NorthNew Zealand
  4. 4.AgResearch LtdPalmerston NorthNew Zealand

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