2-Deoxy-D-glucose
Encyclopedia
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 autoradiograph
y, sometimes in tandem with either conventional or electron microscopy.
2-DG is uptaken by the glucose transporter
s 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 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
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. 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. 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 ray
s, 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.
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
which has the 2-hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group replaced by hydrogen, so that it cannot undergo further glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
. Glucose hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
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
Tritium
Tritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...
or carbon-14
Carbon-14
Carbon-14, 14C, or radiocarbon, is a radioactive isotope of carbon with a nucleus containing 6 protons and 8 neutrons. Its presence in organic materials is the basis of the radiocarbon dating method pioneered by Willard Libby and colleagues , to date archaeological, geological, and hydrogeological...
has been a popular ligand for laboratory research in animal models, where distribution is assessed by tissue-slicing followed by autoradiograph
Autoradiograph
An autoradiograph is an image on an x-ray film or nuclear emulsion produced by the pattern of decay emissions from a distribution of a radioactive substance...
y, sometimes in tandem with either conventional or electron microscopy.
2-DG is uptaken by the glucose transporter
Glucose transporter
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla...
s 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
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
therapeutic has been suggested, and in fact, 2-DG is in clinical trials 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
Work on the ketogenic diet
Ketogenic diet
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control epilepsy in children. The diet mimics aspects of starvation by forcing the body to burn fats rather than carbohydrates...
as a treatment for epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
have investigated the role of glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
in the disease. 2-Deoxyglucose has been proposed by Garriga-Canut et al. as a mimic for the ketogenic diet
Ketogenic diet
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control epilepsy in children. The diet mimics aspects of starvation by forcing the body to burn fats rather than carbohydrates...
, and shows great promise as a new anti-epileptic drug. The authors suggest that 2-DG works, in part, by decreasing the expression of Brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...
(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. In clinical medical imaging (PET scanning), fluorodeoxyglucose
Fluorodeoxyglucose
Fludeoxyglucose or fluorodeoxyglucose , commonly abbreviated 18F-FDG or FDG, is a radiopharmaceutical used in the medical imaging modality positron emission tomography...
is used, where one of the 2-hydrogens of 2-deoxy-D-glucose is replaced with the positron-emitting isotope fluorine-18
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
, which emits paired gamma ray
Gamma ray
Gamma radiation, also known as gamma rays or hyphenated as gamma-rays and denoted as γ, is electromagnetic radiation of high frequency . Gamma rays are usually naturally produced on Earth by decay of high energy states in atomic nuclei...
s, allowing distribution of the tracer to be imaged by external gamma camera(s). This is increasingly done in tandem with a CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
function which is part of the same PET/CT machine, to allow better localization of small-volume tissue glucose-uptake differences.