2-Deoxy-D-glucose

2-Deoxy-D-glucose[1]
IUPAC name

(4R,5S,6R)-6-(hydroxymethyl)oxane-2,4,5-triol
Other names

2-Deoxyglucose
2-Deoxy-D-mannose
2-Deoxy-D-arabino-hexose
2-DG
Identifiers
CAS number 154-17-6 Y
ChemSpider 388402 Y
UNII 9G2MP84A8W Y
Jmol-3D images Image 1
Properties
Molecular formula C6H12O5
Molar mass 164.16 g/mol
Melting point

142–144 °C
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Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

2-Deoxy-D-glucose is a glucose molecule which has the 2-hydroxyl group replaced by hydrogen, so that it cannot undergo further glycolysis. Glucose hexokinase traps this substance in most cells (with exception of liver and kidney) so that it makes a good marker for tissue glucose use and hexokinase activity. Many cancers have elevated glucose uptake and hexokinase levels. 2-Deoxyglucose labeled with tritium or carbon-14 has been a popular ligand for laboratory research in animal models, where distribution is assessed by tissue-slicing followed by autoradiography, sometimes in tandem with either conventional or electron microscopy.

2-DG is uptaken by the glucose transporters of the cell. Therefore, cells with higher glucose uptake, for example tumor cells, have also a higher uptake of 2-DG. Since 2-DG hampers cell growth, its use as a tumor therapeutic has been suggested, and in fact, 2-DG is in clinical trials [2] However, it is not completely clear how 2-DG inhibits cell growth. The fact that glycolysis is inhibited by 2-DG, seems not to be sufficient to explain why 2-DG treated cells stop growing [3]

Work on the ketogenic diet as a treatment for epilepsy have investigated the role of glycolysis in the disease. 2-Deoxyglucose has been proposed by Garriga-Canut et al. as a mimic for the ketogenic diet, and shows great promise as a new anti-epileptic drug.[4] The authors suggest that 2-DG works, in part, by decreasing the expression of Brain-derived neurotrophic factor (BDNF). Such uses are complicated by the fact that 2-deoxyglucose does have some toxicity.

2-DG has been used as a targeted optical imaging agent for fluorescent in vivo imaging.[5][6] In clinical medical imaging (PET scanning), fluorodeoxyglucose is used, where one of the 2-hydrogens of 2-deoxy-D-glucose is replaced with the positron-emitting isotope fluorine-18, which emits paired gamma rays, allowing distribution of the tracer to be imaged by external gamma camera(s). This is increasingly done in tandem with a CT function which is part of the same PET/CT machine, to allow better localization of small-volume tissue glucose-uptake differences.

References

  1. ^ Merck Index, 11th Edition, 2886.
  2. ^ Pelicano, H; Martin, DS; Xu, RH; Huang, P (2006). "Glycolysis inhibition for anticancer treatment". Oncogene 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078. 
  3. ^ M Ralser, MM Wamelink, EA Struys, C Joppich, S Krobitsch, C Jakobs, H Lehrach Proc Natl Acad Sci U S A, 2008, doi:10.1073/pnas.0803090105
  4. ^ Mireia Garriga-Canut, Barry Schoenike, Romena Qazi, Karen Bergendahl, Timothy J Daley, Rebecca M Pfender, John F Morrison, Jeffrey Ockuly, Carl Stafstrom, Thomas Sutula & Avtar Roopra, "2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure", Nat Neurosci, 9, 1382 - 1387 (2006). doi:10.1038/nn1791 Garriga-Canut, M.; Schoenike, B.; Qazi, R.; Bergendahl, K.; Daley, T. J.; Pfender, R. M.; Morrison, J. F.; Ockuly, J. et al. (2006). "2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure". Nature Neuroscience 9 (11): 1382–1387. doi:10.1038/nn1791. PMID 17041593.  edit
  5. ^ Kovar, J., Volcheck, W., Sevick-Muraca, E., Simpson, M.A., and Olive, D.M., Analytical Biochemistry, Vol. 384 (2009) 254-262 Download PDF
  6. ^ Cheng, Z., Levi, J., Xiong, Z., Gheysens, O., Keren, S., Chen, X., and Gambhir, S., Bioconjugate Chemistry, 17(3), (2006), 662-669