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Gene Review

HK1  -  hexokinase 1

Homo sapiens

Synonyms: Brain form hexokinase, HK I, HK1-ta, HK1-tb, HK1-tc, ...
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Disease relevance of HK1


Psychiatry related information on HK1


High impact information on HK1


Chemical compound and disease context of HK1


Biological context of HK1


Anatomical context of HK1


Associations of HK1 with chemical compounds


Physical interactions of HK1


Co-localisations of HK1


Regulatory relationships of HK1


Other interactions of HK1

  • Mean red cell G-6-PD, PK, ALD, and HK levels remained mildly to moderately elevated at 11 to 12 months of life, suggesting the persistence of a relatively young red cell population throughout the first year of life [39].
  • The gene for hexokinase II, HK2, has been previously mapped to human chromosome 2p13 by fluorescence in situ hybridization, and two-point linkage analysis has placed it near the locus for transforming growth factor alpha, TGFA [1].
  • Expression of hexokinase 1 and hexokinase 2 in mammary tissue of nonlactating and lactating rats: evaluation by RT-PCR [18].
  • The RBC of term and preterm babies showed higher GSH, GSSG, G-6-PDH, GR, and HK levels/activities and lower GSH/GSSG ratios and higher GSH-recycling rates than those of adults [40].
  • In the present paper, a direct interaction of HK-I with bilayer-reconstituted purified VDAC, inducing channel closure, is demonstrated for the first time [35].

Analytical, diagnostic and therapeutic context of HK1

  • When RBC of increasing age was separated by buoyant density ultracentrifugation, the total HK activity decayed in a biphasic manner, with half-lives respectively of approximately 15 and approximately 51 days [22].
  • The hexokinase (HK) of the human red blood cell (RBC) was separated into two distinct major isozymes by fast protein liquid chromatography using a linear salt gradient on a MonoQ column [22].
  • From a gel filtration column, HKR eluted before HKI, suggesting that it was larger than HKI by several kilodaltons [22].
  • Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation [25].
  • In the whole population HK and G6PDH activities inversely correlated with fasting and 2-h OGTT plasma glucose levels [41].


  1. A novel (TA)n polymorphism in the hexokinase II gene: application to noninsulin-dependent diabetes mellitus in the Pima Indians. Ardehali, H., Tiller, G.E., Printz, R.L., Mochizuki, H., Prochazka, M., Granner, D.K. Hum. Genet. (1996) [Pubmed]
  2. Mammalian hexokinases and their abnormal expression in cancer. Smith, T.A. Br. J. Biomed. Sci. (2000) [Pubmed]
  3. Hexokinase isoenzymes in the diagnosis of gastric and esophageal neoplasms. Bassalyk, L.S., Ljubimova, N.V. Neoplasma (1987) [Pubmed]
  4. Activities of key glycolytic enzymes in the brains of patients with Alzheimer's disease. Bigl, M., Brückner, M.K., Arendt, T., Bigl, V., Eschrich, K. Journal of neural transmission (Vienna, Austria : 1996) (1999) [Pubmed]
  5. The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene. Gessler, M., Grupe, A., Grzeschik, K.H., Pongs, O. Hum. Genet. (1992) [Pubmed]
  6. Human beta-cell glucokinase. Dual role of Ser-151 in catalysis and hexose affinity. Xu, L.Z., Harrison, R.W., Weber, I.T., Pilkis, S.J. J. Biol. Chem. (1995) [Pubmed]
  7. Enzyme activity patterns of energy supplying metabolism in the quadriceps femoris muscle (vastus lateralis): sedentary men and physically active men of different performance levels. Bass, A., Vondra, K., Rath, R., Vítek, V., Teisinger, J., Macková, E., Sprynarová, S., Malkovská, M. Pflugers Arch. (1976) [Pubmed]
  8. Glycolytic enzymes from human autoptic brain cortex: normal aged and demented cases. Iwangoff, P., Armbruster, R., Enz, A., Meier-Ruge, W. Mech. Ageing Dev. (1980) [Pubmed]
  9. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. Cline, G.W., Petersen, K.F., Krssak, M., Shen, J., Hundal, R.S., Trajanoski, Z., Inzucchi, S., Dresner, A., Rothman, D.L., Shulman, G.I. N. Engl. J. Med. (1999) [Pubmed]
  10. Isoenzymes of hexokinase in human muscular dystrophy. Strickland, J.M., Ellis, D.A. Nature (1975) [Pubmed]
  11. A new ATP-binding fold in actin, hexokinase and Hsc70. Holmes, K.C., Sander, C., Valencia, A. Trends Cell Biol. (1993) [Pubmed]
  12. The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle. Kelley, D.E., Mintun, M.A., Watkins, S.C., Simoneau, J.A., Jadali, F., Fredrickson, A., Beattie, J., Thériault, R. J. Clin. Invest. (1996) [Pubmed]
  13. Impaired activity and gene expression of hexokinase II in muscle from non-insulin-dependent diabetes mellitus patients. Vestergaard, H., Bjørbaek, C., Hansen, T., Larsen, F.S., Granner, D.K., Pedersen, O. J. Clin. Invest. (1995) [Pubmed]
  14. Glucose 6-phosphate release of wild-type and mutant human brain hexokinases from mitochondria. Skaff, D.A., Kim, C.S., Tsai, H.J., Honzatko, R.B., Fromm, H.J. J. Biol. Chem. (2005) [Pubmed]
  15. Crystallization and preliminary X-ray analysis of human brain hexokinase. Aleshin, A.E., Zeng, C., Fromm, H.J., Honzatko, R.B. FEBS Lett. (1996) [Pubmed]
  16. Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines. Yasumoto, E., Nakano, K., Nakayachi, T., Morshed, S.R., Hashimoto, K., Kikuchi, H., Nishikawa, H., Kawase, M., Sakagami, H. Anticancer Res. (2004) [Pubmed]
  17. Malarial parasite hexokinase and hexokinase-dependent glutathione reduction in the Plasmodium falciparum-infected human erythrocyte. Roth, E.F. J. Biol. Chem. (1987) [Pubmed]
  18. Expression of hexokinase 1 and hexokinase 2 in mammary tissue of nonlactating and lactating rats: evaluation by RT-PCR. Kaselonis, G.L., McCabe, E.R., Gray, S.M. Mol. Genet. Metab. (1999) [Pubmed]
  19. Shared synteny between human chromosome 10 and chromosome 1 of the marsupial tammar wallaby, Macropus eugenii. Spurdle, A.B., Maccarone, P., Toder, R., Wilcox, S.A., Graves, J.A. Cytogenet. Cell Genet. (1997) [Pubmed]
  20. Identification of the cDNA for human red blood cell-specific hexokinase isozyme. Murakami, K., Piomelli, S. Blood (1997) [Pubmed]
  21. Hexokinase II: the integration of energy metabolism and control of apoptosis. Pastorino, J.G., Hoek, J.B. Current medicinal chemistry. (2003) [Pubmed]
  22. An isozyme of hexokinase specific for the human red blood cell (HKR). Murakami, K., Blei, F., Tilton, W., Seaman, C., Piomelli, S. Blood (1990) [Pubmed]
  23. The voltage-dependent anion channel-1 modulates apoptotic cell death. Zaid, H., Abu-Hamad, S., Israelson, A., Nathan, I., Shoshan-Barmatz, V. Cell Death Differ. (2005) [Pubmed]
  24. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. Bos, R., van Der Hoeven, J.J., van Der Wall, E., van Der Groep, P., van Diest, P.J., Comans, E.F., Joshi, U., Semenza, G.L., Hoekstra, O.S., Lammertsma, A.A., Molthoff, C.F. J. Clin. Oncol. (2002) [Pubmed]
  25. Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue. Gudnason, V., Ingvarsson, S., Jonasdottir, A., Andresdottir, V., Egilsson, V. Int. J. Cancer (1984) [Pubmed]
  26. Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms. Blachly-Dyson, E., Baldini, A., Litt, M., McCabe, E.R., Forte, M. Genomics (1994) [Pubmed]
  27. A population association study of four candidate genes (hexokinase II, glucagon-like peptide-1 receptor, fatty acid binding protein-2, and apolipoprotein C-II) with type 2 diabetes and impaired glucose tolerance in Japanese subjects. Yagi, T., Nishi, S., Hinata, S., Murakami, M., Yoshimi, T. Diabet. Med. (1996) [Pubmed]
  28. Frequency of glucose-6-phosphate dehydrogenase, pyruvate kinase and hexokinase deficiency in the Saudi population. el-Hazmi, M.A., Al-Swailem, A.R., Al-Faleh, F.Z., Warsy, A.S. Hum. Hered. (1986) [Pubmed]
  29. Evaluation of the role of hexokinase type II in cellular proliferation and apoptosis using human hepatocellular carcinoma cell lines. Ahn, K.J., Hwang, H.S., Park, J.H., Bang, S.H., Kang, W.J., Yun, M., Lee, J.D. J. Nucl. Med. (2009) [Pubmed]
  30. Gaucher disease. III. Substrate specificity of glucocerebrosidase and the use of nonlabeled natural substrates for the investigation of patients. Choy, F.Y., Davidson, R.G. Am. J. Hum. Genet. (1980) [Pubmed]
  31. Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Rothman, D.L., Magnusson, I., Cline, G., Gerard, D., Kahn, C.R., Shulman, R.G., Shulman, G.I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  32. Cellular mechanisms of insulin resistance in humans. Shulman, G.I. Am. J. Cardiol. (1999) [Pubmed]
  33. Study on ATP-generating system and related hexokinase activity in mitochondria isolated from undifferentiated or differentiated HT29 adenocarcinoma cells. Gauthier, T., Denis-Pouxviel, C., Paris, H., Murat, J.C. Biochim. Biophys. Acta (1989) [Pubmed]
  34. Hexose transporters GLUT1 and GLUT3 are colocalized with hexokinase I in caveolae microdomains of rat spermatogenic cells. Rauch, M.C., Ocampo, M.E., Bohle, J., Amthauer, R., Yáñez, A.J., Rodríguez-Gil, J.E., Slebe, J.C., Reyes, J.G., Concha, I.I. J. Cell. Physiol. (2006) [Pubmed]
  35. In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death. Azoulay-Zohar, H., Israelson, A., Abu-Hamad, S., Shoshan-Barmatz, V. Biochem. J. (2004) [Pubmed]
  36. Peroxisome Function Regulates Growth on Glucose in the Basidiomycete Fungus Cryptococcus neoformans. Idnurm, A., Giles, S.S., Perfect, J.R., Heitman, J. Eukaryotic Cell (2007) [Pubmed]
  37. Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury. Ahmad, A., Ahmad, S., Schneider, B.K., Allen, C.B., Chang, L.Y., White, C.W. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  38. Importance of cell aggregation for expression of liver functions and regeneration demonstrated with primary cultured hepatocytes. Yuasa, C., Tomita, Y., Shono, M., Ishimura, K., Ichihara, A. J. Cell. Physiol. (1993) [Pubmed]
  39. Red cell metabolic alterations in postnatal life in term infants: glycolytic enzymes and glucose-6-phosphate dehydrogenase. Travis, S.F., Kumar, S.P., Paez, P.C., Delivoria-Papadopoulos, M. Pediatr. Res. (1980) [Pubmed]
  40. Glutathione recycling and antioxidant enzyme activities in erythrocytes of term and preterm newborns at birth. Frosali, S., Di Simplicio, P., Perrone, S., Di Giuseppe, D., Longini, M., Tanganelli, D., Buonocore, G. Biol. Neonate (2004) [Pubmed]
  41. Mononuclear leukocytes from obese patients with type II diabetes have reduced activity of hexokinase, 6-phosphofructokinase and glucose-6-phosphate dehydrogenase. Muggeo, M., Moghetti, P., Querena, M., Cacciatori, V., Zoppini, G., Zenere, M., Tosi, F., Travia, D., Bonora, E. Horm. Metab. Res. (1993) [Pubmed]
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