• June 13, 2024
Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy

Hexokinase-2 bound to mitochondria: cancer’s stygian link to the “Warburg Effect” and a pivotal target for effective therapy

The commonest metabolic hallmark of malignant tumors, i.e., the “Warburg impact” is their propensity to metabolize glucose to lactic acid at a excessive charge even within the presence of oxygen. The pivotal participant on this frequent most cancers phenotype is mitochondrial-bound hexokinase [Bustamante E, Pedersen PL. High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci USA 1977;74(9):3735-9; Bustamante E, Morris HP, Pedersen PL. Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. J Biol Chem 1981;256(16):8699-704]. Now, in clinics worldwide this outstanding phenotype types the idea of one of the crucial widespread detection techniques for most cancers, i.e., positron emission tomography (PET). Considerably, HK-2 is the main sure hexokinase isoform expressed in cancers that exhibit a “Warburg impact”. This consists of most cancers that metastasize and kill their human host. By stationing itself on the outer mitochondrial membrane, HK-2 additionally helps immortalize most cancers cells, escapes product inhibition and features preferential entry to newly synthesized ATP for phosphorylating glucose.
Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy
Hexokinase-2 sure to mitochondria: most cancers’s stygian hyperlink to the “Warburg Impact” and a pivotal goal for efficient remedy
The resultant acidity possible wards off an immune response whereas getting ready surrounding tissues for invasion. With the re-emergence and acceptance of each the “Warburg impact” as a outstanding phenotype of most medical cancers, and “metabolic concentrating on” as a rational therapeutic technique, quite a few laboratories are specializing in metabolite entry or exit steps.

One exceptional success story [Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA, Torbenson MS, et al. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem Biophys Res Commun 2004;324(1):269-75] is using the small molecule 3-bromopyruvate (3-BP) that selectively enters and destroys the cells of huge tumors in animals by concentrating on each HK-2 and the mitochondrial ATP synthasome.
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