Tumor metabolism is associated with increase in glycolytic pathways by what is known as the Warburg effect. The lack of oxygen due to decreased vascularization makes the mutated cells rely on an anaerobic production of lactate from pyruvate by lactate dehydrogenase accompanied by the oxidation of NADH to NAD+, with a net production of 2 ATP as their main energy source. The NAD+ produced is used as an electron acceptor by the mitochondrial transport chain requiring a stable and high concentration requiring the constant production of lactate. This mechanism results in the accumulation and secretion of lactate, making the tissue and its’ surroundings slightly more acidic than healthy cells, known as tumor acidosis (Akhenblit, 2016).
Clinical studies have suggested an association between the drug metformin and a reduction or control of tumors in diabetes 2 mellitus patients, but the lack of noninvasive research methods have interrupted further progress in the investigation of this potential side effect of the drug. Metformin is a vastly used drug to decrease glucose production, however its’ mechanism of action is still controversial.
The drug enters the cell through an OCT membrane transporter, and studies …show more content…
This means finding proteins that express affinity and specificity for the respective ligand. According to Ewald (2011) there are three good options, CitX (periplasmic binding protein from Salmonella typhimurium) and the binding domains of DpiB (sensor histidine kinase from E. coli) and CitA (sensor histidine kinase from Klebsiella pneumoniae). We would then purify all three proteins and record fluorescence energy values when bound to citrate for future reference. It is also crucial to test the purified proteins affinity against pyruvate and other citric acid cycle metabolites such as succinate and α-ketoglutarate, to prevent false positive results from occurring (Ewald,
Clinical studies have suggested an association between the drug metformin and a reduction or control of tumors in diabetes 2 mellitus patients, but the lack of noninvasive research methods have interrupted further progress in the investigation of this potential side effect of the drug. Metformin is a vastly used drug to decrease glucose production, however its’ mechanism of action is still controversial.
The drug enters the cell through an OCT membrane transporter, and studies …show more content…
This means finding proteins that express affinity and specificity for the respective ligand. According to Ewald (2011) there are three good options, CitX (periplasmic binding protein from Salmonella typhimurium) and the binding domains of DpiB (sensor histidine kinase from E. coli) and CitA (sensor histidine kinase from Klebsiella pneumoniae). We would then purify all three proteins and record fluorescence energy values when bound to citrate for future reference. It is also crucial to test the purified proteins affinity against pyruvate and other citric acid cycle metabolites such as succinate and α-ketoglutarate, to prevent false positive results from occurring (Ewald,