Now that 2-Deoxy-D-Glucose is available over the counter at Rs 990/- ,we shall review the drug and find out facts from fictions around the new molecule.
2DG is not new. It is a repurposed drug. It has been long used in cancer chemotherapy till date. Let’s see how will it perform against Covid-19.
The manufacturer’s instructions to use the drug is given below.
2-DG is an imposter, a Glucose look-alike. Unlike normal Glucose, It produces no energy. It can replace glucose in cells and thus allow cells to starve to death. There is also an alternative mannose pathway which is also toxic to cells. So 2-DG is a Glucose look alike human cell poison.
Life can exist without Oxygen.
Billion years ago, when oxygen has not appeared in the atmosphere, life existed by and was nourished by a primitive method ie. Anaerobic Glycolysis. The word anaerobic glycolysis literally means breaking down of Glucose when oxygen is not available.
Anaerobic Glycolysis has survived a billion years of evolution and still functions inside our body, but in special situations.
Very Inefficient method–
While one Glucose molecule in the presence Oxygen release 30 units of energy, (ATP) anaerobic glycolysis can muster only two. It may be the most inefficient technology, but can save our life in special situations like drowning, chocking etc. You have to consume 15 times more glucose and still can get cramps in legs due to one of its side effect. Yes the cramps that athletes get at the height of some sporting excellence is one such example.
Applying to Covid Pneumonia-
In Covid Pneumonia, oxygen saturations fall and cells clogged with the virus resort to this billion years old method. Cells that are exposed to Oxygen saturation less than 80 are forced to consume 15 times more glucose than the normal cells. If we replace the normal glucose with an Imposter 2 Deoxy D Glucose, hypoxic cells will voraciously devour them, 15 times more than other cells.
( The following two paragraphs are tecnical description of the drug and its modus operandi- may Skip. )
Source: https://doi.org/10.1002/iub.1251
[ The wonders of 2-Deoxy-D-Glucose, International union of biochemistry and molecular biology Volume 66, number 2 ]
( 2-DG exploits a universal trait of cells in which the upregulation of glucose uptake and metabolism has started. For example, it supports uncontrolled proliferation by providing the nucleotide building blocks via the PPS, reprograms energy metabolism by aerobic glycolysis, and maintains ER homeostasis through proper glycosylation, and so forth. By mimicking glucose, 2-DG offers a natural means of exploiting increased glucose metabolism. However, as under norm-oxia other energy sources can be used to fuel cells and sustain their viability, 2-DG’s toxicity is more limited to cells under hypoxia. Although under norm-oxia most tumor cells are growth inhibited by 2-DG treatment, we as well as others have found that a select number of tumor cell types in this environmental condition undergo ER stress-induced cell death. Therefore, 2-DG holds much promise for treating most if not all cancer types. Oncogenic events are indicated by rectangles and metabolic enzymes by circles. )
Abbreviations: 2-DG, 2-deoxy-d-glucose; 2-DG-6-P, 2-deoxy-d-glucose-6-phosphate; ER, endoplasmic reticulum; F-6-P, fructose-6-phosphate; G-6-P, glucose-6-phosphate; HK, hexokinase; M-6-P, mannose-6-phosphate; PGI, phosphoglucose isomerase; PMI, phosphomannose isomerase; PPS, pentose phosphate shunt.)
Caveat–
2-DG is an imposter. It does not produce any energy. It kills cells in low oxygen environments by depriving them of their nutrient. But when the patient’s saturation falls below 80, every cell in his body will be hypoxic. That includes brain cells also which thrive only on glucose nothing else. What will be the effect of 2-DG on our hypoxic brain cells ? We can only know when it is used on at least 30-40 thousand patients, not before that.
Till such time, I keep my fingers crossed.
Good day.
Dr Ramakanta's Ideas 