Back from holidays. 2DG metabolism.

According to the Drug Information of NIH, the full name of 2-DG is 2-Deoxy-D-glucose and it is described there as "An antimetabolite of glucose with antiviral activity". Due to its prominent anti-gucose activity, the 2-DG as a drug has been on several clinical trials concerning anti-metabolic approach to cancer treatment since cancerous cells are extremely dependent on glucose as an energy substrate while most other cell types can  adjust their energy use switching to alternative substrates such as ketone bodies. See clinical trials concerning 2-DG at http://clinicaltrials.gov/ct2/results?recr=Open&intr=2-DEOXYGLUCOSE


2-DEOXY-D-GLUCOSE (2-DG) is a synthetic glucose analogue that competes with glucose for transport into the cells and competitively inhibits the intracellular metabolism of glucose (1) in all tissues studied and especially in the brain  (2), is phosphorylated to 2-deoxy-D-glucose 6-phosphate (DOG6P) but is not further metabolized (2). 2-DG molecule cannot bemetabolized via the glycolytic pathway so it gradually accumulates within the cell, causing  inhibition of glucose-6-phosphate isomerase and the subsequent blockade of the conversion from glucose-6-phosphate to fructose-6-phosphate, a crucial step in this metabolic pathway (1).


By inhibiting glycolysis, 2-DG indirectly helps producing ketone bodies and this way, it can be considered an anti-epileptic drug. However, it also results in a metabolic crisis, which is a known pro-epileptic condition so there's no consensus regarding this aspect of 2-DG as a drug (3).


Sources:




1. R. W. HORTON et al., J  Neurochem, 1973, Vol. 21, 5O7-520
2. SOLS A  and CRANER  K.  J. biol. Chem. 1954 210,581-595
3. Gasior et al., Epilepsia, 2010, 1–10,
(doi: 10.1111/j.1528-1167.2010.02593.x)

Glycolysis Overview BioFiles 2007, 2.6, 4. Carbohydrates synthesized during photosynthesis act as the main storage molecules of solar energy. When ingested, complex carbohydrates are enzymatically hydrolyzed to monosaccharides, such as starch to D(+)-glucose. The catabolism of glucose is the primary energy source for shortterm requirements and begins with the Embden-Meyerhoff-Pathway as illustrated in Figure 1. D(+)-Glucose (1) is phosphorylated in the first reaction with ATP to give glucose-6-phosphate (2). Figure 1. Embden-Meyerhoff-Pathway The isomerization of glucose-6-phosphate (2) in the second reaction to fructose-6-phosphate (3) occurs via ring-opening and subsequent keto-enol-tautomerization. The third reaction is another phosphorylation with ATP, whereby fructose-6-phosphate (3) is converted to fructose-1,6-bisphosphate (4). A key branching reaction is the fourth reaction: a ring-opening reaction of fructose-1,6-bisphosphate (4), which is cleaved in a retro-aldol reaction into D-glyceraldehyde-3-phosphate (5), and dihydroxyacetone phosphate (6). The branch via dihydroxyacetonephosphate (6) is channelled back into D-glyceraldehyde-3-phosphate (5) in the fifth reaction by an isomerization. In the sixth reaction the combined D-glyceraldehyde- 3-phosphate from both routes is oxidized at the C1 to a carboxylic acid and then phosphorylated in the 1-position to yield 1,3-bisphospho-D-glycerate (7). This phosphate group in the 1-position is transferred in the seventh reaction from the carboxyl group of (7) to ADP to give 3-phospho-D-glycerate (8). The eighth reaction is an isomerization of 3-phospho-D-glycerate (8) to 2-phospho-D-glycerate (9). The next metabolite phosphoenolpyruvate (10) is formed in a dehydration reaction from 2-phospho-D-glycerate in the ninth reaction. The glycolysis pathway from D(+)-glucose (1) to two molecules of pyruvate (11) is concluded by the tenth reaction, which transfers a phosphate group from phosphoenolpyruvate (10) to ADP, thereby giving ATP and pyruvate (11). Visit the Sigma Metabolomics Resource Center to view the Nicholson-IUBMB animation of glycolysis at http://www.sigma.com/metpath.