We're Not "DON" Yet: Optimal Dosing and Prodrug Delivery of 6-Diazo-5-oxo-L-norleucine ... - 0 views
-
Glutamine is the most abundant amino acid in blood
-
Rapidly proliferating healthy cells (GI epithelium, lymphocytes) or cells under physiologic stress have increased demand for glutamine
-
Glutamine is transported into cells by one of multiple amino acid transporters (e.g. ASCT2, BOAT2), several of which are thought to be upregulated in cancer cells
- ...10 more annotations...
-
Glutamate, produced from glutamine by glutaminase and glutamine amidotransferase activities, may be further metabolized to alpha ketoglutarate and provide a carbon skeleton source for the mitochondrial tricarboxylic acid cycle (TCA cycle)
-
Glutamine-derived glutamate is also involved in the synthesis of the reducing equivalent glutathione, vital to maintaining cellular redox status
-
Many tumors become largely dependent on glutamine to provide carbon and nitrogen building blocks needed for proliferation
-
In cancer model systems, Eagle and colleagues first demonstrated tumor cells in culture require supplementation with exogenous glutamine for efficient proliferation
-
The most well-characterized oncogene to regulate glutamine metabolism is MYC (9), which enhances glutaminase expression, upregulates glutamine transporters, and enhances glutamine utilization in energy production and biosynthesis
-
Other pro-tumorigenic regulators such as KRAS and mTOR, as well as tumor suppressors (p53, VHL) have also been associated with alterations in glutamine metabolism
-
Tumor cells are highly adaptable and alter nutrient uptake and metabolic networks to resist single agent glutaminase inhibition
-
cells in the microenvironment of several tumor types upregulate glutamine production, thereby enabling tumor cells to escape glutaminase inhibition