BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Enzymatic properties of the N- and C-terminal halves of human hexokinase II

  • Ahn, Keun-Jae (Division of Nuclear Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science) ;
  • Kim, Jong-Sun (Department of Microbiology, Yonsei University College of Medicine) ;
  • Yun, Mi-Jin (Division of Nuclear Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science) ;
  • Park, Jeon-Han (Department of Microbiology, Yonsei University College of Medicine) ;
  • Lee, Jong-Doo (Division of Nuclear Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science)
  • Published : 2009.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Although previous studies on hexokinase (HK) II indicate both the N- and C-terminal halves are catalytically active, we show in this study the N-terminal half is significantly more catalytic than the C-terminal half in addition to having a significantly higher $K_m$ for ATP and Glu. Furthermore, truncated forms of intact HK II lacking its first N-terminal 18 amino acids ($\Delta$18) and a truncated N-terminal half lacking its first 18 amino acids ($\Delta$18N) have higher catalytic activity than other mutants tested. Similar results were obtained by PET-scan analysis using $^{18}F-FDG$. Our results collectively suggest that each domain of HK II possesses enzyme activity, unlike HK I, with the N-terminal half showing higher enzyme activity than the C-terminal half.

Keywords

References

  1. Wilson, J. E. (1995) Hexokinases. Rev. Physiol. Biochem. Pharmacol. 126, 65-198 https://doi.org/10.1007/BFb0049776
  2. Cardenas, M. L., Cornish-Bowden, A. and Ureta, T. (1998) Evolution and regulatory role of the hexokinases. Biochim. Biophys. Acta. 1401, 242-264 https://doi.org/10.1016/S0167-4889(97)00150-X
  3. Ardehali, H., Yano, Y., Printz, R. L., Koch, S., Whitesell, R. R., May, J. M. and Granner, D. K. (1996) Functional organization of mammalian hexokinase II. Retention of catalytic and regulatory functions in both the NH2- and COOH-terminal halves. J. Biol. Chem. 271, 1849-1852 https://doi.org/10.1074/jbc.271.4.1849
  4. Postic, C., Shiota, M. and Magnuson, M. A. (2001) Cell- specific roles of glucokinase in glucose homeostasis. Recent Prog. Horm. Res. 56, 195-217 https://doi.org/10.1210/rp.56.1.195
  5. Bork, P., Sander, C. and Valencia, A. (1993) Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases. Protein Sci. 2, 31-40 https://doi.org/10.1002/pro.5560020104
  6. Schwab, D. A. and Wilson, J. E. (1989) Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase. Proc. Natl. Acad. Sci. U.S.A. 86, 2563-2567 https://doi.org/10.1073/pnas.86.8.2563
  7. Frohlich, K., Entian, K. and Mecke, D. (1985) The primary structure of the yeast hexokinase PII gene (HXK2) which is responsible for glucose repression. Gene 36, 105-111 https://doi.org/10.1016/0378-1119(85)90074-5
  8. White, T. K. and Wilson, J. E. (1989) Isolation and characterization of the discrete N- and C-terminal halves of rat brain hexokinase: retention of full catalytic activity in the isolated C-terminal half. Arch. Biochem. Biophys. 274, 373-393
  9. Arora, K. K. and Pedersen, P. L. (1993) Glucose utilization by tumor cells: the enzyme hexokinase autophosphorylates both its N- and C-terminal halves. Arch. Biochem. Biophys. 304, 515-518 https://doi.org/10.1006/abbi.1993.1384
  10. Wilson, J. E. (1997) An introduction to the isoenzymes of mammalian hexokinase types I-III. Biochem. Soc. Trans. 25, 103-108 https://doi.org/10.1042/bst0250103
  11. Gelb, B. D., Adams, V., Jones, S. N., Griffin, L. D., MacGregor, G. R. and McCabe, E. R. B. (1992) Targeting of hexokinase 1 to liver and hepatoma mitochondria. Proc. Natl. Acad. Sci. U.S.A. 89, 202-206 https://doi.org/10.1073/pnas.89.1.202
  12. Bianchi, M., Serafini, G., Bartolucci, E., Giammarini, C. and Magnani, M. (1998) Enzymatic properties of overexpressed human hexokinase fragments. Mol. Cell Biochem. 189, 185-193 https://doi.org/10.1023/A:1006962217495
  13. Polakis, P. G. and Wilson, J. E. (1985) An intact hydrophobic N-terminal sequence is critical for binding of rat brain hexokinase to mitochondria. Arch. Biochem. Biophys. 236, 328-337 https://doi.org/10.1016/0003-9861(85)90633-2
  14. Tsai, H. J. and Wilson, J. E. (1995) Functional organization of mammalian hexokinases: characterization of chimeric hexokinases constructed from the N- and C-terminal domains of the rat type I and type II isozymes. Arch. Biochem. Biophys. 316, 206-214 https://doi.org/10.1006/abbi.1995.1029
  15. Tsai, H. J. and Wilson, J. E. (1996) Functional organization of mammalian hexokinases: both N- and C-terminal halves of the rat type II isozyme possess catalytic sites. Arch. Biochem. Biophys. 329, 17-23 https://doi.org/10.1006/abbi.1996.0186
  16. Colowick, S. P. (1973) The hexokinases. In PD Boyer, (ed) pp. 1-48, The Enzymes, Vol 9. Academic Press, New York, USA
  17. Easterby, J. and O'Brien, M. (1973) Purification and properties of pig-heart hexokinase. Eur. J. Biochem. 38, 201-211 https://doi.org/10.1111/j.1432-1033.1973.tb03051.x
  18. Di Chiro, G., DeLaPaz, R. L., Brooks, R. A., Sokoloff, L., Kornblith, P. L., Smith, B. H., Patronas, N. J., Kufta, C. V., Kessler, R. M., Johnston, G. S., Manning, R. G. and Wolf, A. P. (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32, 1323-1329 https://doi.org/10.1212/WNL.32.12.1323
  19. Ureta, T. (1982) The comparative isozymology of vertebrate hexokinases. Comp. Biochem. Physiol. B. 71B, 549-555
  20. Aleshin, A. E., Zeng, C. and Bartunik, H. D. (1998) Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate. J. Mol. Biol. 282, 345-357 https://doi.org/10.1006/jmbi.1998.2017
  21. Tsai, H. J. (1999) Functional organization and evolution of mammalian hexokinases: mutations that caused the loss of catalytic activity in N-terminal halves of type I and type III isozymes. Arch. Biochem. Biophys. 369, 149-156 https://doi.org/10.1006/abbi.1999.1326
  22. Ardehali, H., Printz, R. L., Whitesell, R. R., May, J. M. and Granner, D. K. (1999) Functional interaction between the N- and C-terminal halves of human hexokinase II. J. Biol. Chem. 274, 15986-15989 https://doi.org/10.1074/jbc.274.23.15986
  23. Maru, Y, Afar, D. E., Witte, O. N. and Shibuya, M. (1996) The dimerization property of glutathione S-transferase partially reactivates Bcr-Abl lacking the oligomerization domain. J. Biol. Chem. 26, 15353-15357
  24. Tudyka, T. and Skerra, A. (1997) Glutathione S-transferase can be used as a C-terminal, enzymatically active dimerization module for a recombinant protease inhibitor, and functionally secreted into the periplasm of Escherichia coli. Protein Sci. 10, 2180-2187
  25. Gambhir, S. S., Czernin, J., Schwimmer, J., Silverman, D. H., Coleman, R. E. and Phelps, M. E. (2001) A tabulated summary of the FDG PET literature. J. Nucl. Med. 42, S1-93
  26. Morris, M. T., DeBruin, C., Yang, Z., Chambers, J. W., Smith, K. S. and Morris, J. C. (2006) Activity of a second Trypanosoma brucei hexokinase is controlled by an 18-amino-acid C-terminal tail. Eukaryot. Cell. 5, 2014-2023 https://doi.org/10.1128/EC.00146-06
  27. Zonouzi, R., Ashtiani, S. K., Hosseinkhani, S. and Baharvand, H. (2006) Kinetic properties of extracted lactate dehydrogenase and creatine kinase from mouse embryonic stem cell- and neonatal-derived cardiomyocytes. J. Biochem. Mol. Biol. 39, 426-431 https://doi.org/10.5483/BMBRep.2006.39.4.426
  28. Vinuela, E., Salas, M. and Sols, A. (1963) Glucokinase and hexokinase in liver in relation to glycogen synthesis. J. Biol. Chem. 238, 1175-1177
  29. Waki, A., Kato, H. and Yano, R. (1998) The importance of glucose transport activity as the rate-limiting step of 2-deoxyglucose uptake in tumor cells in vitro. Nucl. Med. Biol. 25, 593-597 https://doi.org/10.1016/S0969-8051(98)00038-9

Cited by

  1. Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis vol.2014, 2014, https://doi.org/10.1155/2014/572097
  2. Modeling cancer glycolysis under hypoglycemia, and the role played by the differential expression of glycolytic isoforms vol.281, pp.15, 2014, https://doi.org/10.1111/febs.12864
  3. Akt Phosphorylates HK-II at Thr-473 and Increases Mitochondrial HK-II Association to Protect Cardiomyocytes vol.288, pp.33, 2013, https://doi.org/10.1074/jbc.M113.482026
  4. Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance vol.24, pp.1, 2016, https://doi.org/10.1016/j.cmet.2016.05.026
  5. Molecular and biochemical characterization of Eimeria tenella hexokinase vol.115, pp.9, 2016, https://doi.org/10.1007/s00436-016-5104-4
  6. Targeting hexokinase 2 in castration-resistant prostate cancer vol.2, pp.3, 2015, https://doi.org/10.4161/23723556.2014.974465
  7. Evaluation of biological properties of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride derivatives and their ability to inhibit hexokinase activity vol.27, pp.3, 2017, https://doi.org/10.1016/j.bmcl.2016.12.055
  8. Zebra Finch Glucokinase Containing Two Homologous Halves Is anIn SilicoChimera vol.2013, 2013, https://doi.org/10.1155/2013/790240
  9. Heterogeneity of glycolysis in cancers and therapeutic opportunities vol.92, pp.1, 2014, https://doi.org/10.1016/j.bcp.2014.07.019
  10. A Unique Hexokinase in Cryptosporidium parvum, an Apicomplexan Pathogen Lacking the Krebs Cycle and Oxidative Phosphorylation vol.165, pp.5, 2014, https://doi.org/10.1016/j.protis.2014.08.002
  11. Expression and role in glycolysis of human ADP-dependent glucokinase vol.364, pp.1-2, 2012, https://doi.org/10.1007/s11010-011-1212-8
  12. Hexokinase II–derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells vol.31, pp.5, 2017, https://doi.org/10.1096/fj.201601173R
  13. Master regulatory role of p63 in epidermal development and disease vol.75, pp.7, 2018, https://doi.org/10.1007/s00018-017-2701-z
  14. The catalytic inactivation of the N-half of human hexokinase 2 and structural and biochemical characterization of its mitochondrial conformation vol.38, pp.1, 2018, https://doi.org/10.1042/BSR20171666