What
is 2-DG?
Q: What is 2-DG? How does it protect against epilepsy? Does it hae to do anything with ketone bodies or ketogenic diet?
Thank you,
Nathan
A: Nathan,
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 clinicaltrials.gov
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)
Tanya Zilberter
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