@haidut
What is going on with the increase in Glutamine intake and the preference for oxidation of that substrate over glucose?
From the study;
"The H4IIEC3 rat hepatoma cell line (American Type Culture Collection, Manassas, VA, USA) was cultured in low glucose DMEM* supplemented with 10% FBS and 1% penicillin/streptomycin antibiotic solution. The glutamine concentration of the culture medium was 2 mmol/L. For fluorescence-based assays, cells were seeded in 96-well plates at 2× 104 cells per well two days prior to experiments to achieve 80%–90% confluency at the time of measurement"
*my note* According to what I see listed by manufacturers online this medium contains 1g/L Glucose. So (1g C6H12O6/180.16g {MM of glucose} = 5.55e-3 moles glucose * 1000 = 5.55 mmol of glucose per L). There is a greater concentration of glucose than glutamine, so the preference for glutamine uptake isn't because there is more glutamine available
"
To further investigate the fuel source driving palmitate-induced mitochondrial activation, we relied on 13C MFA to map the flow of carbon entering the CAC from the major non-lipid substrates glucose and glutamine. We found that glutamine provided the primary fuel for elevated mitochondrial metabolism in the presence of palmitate, rather than fatty acid beta-oxidation, and that glutamine consumption could be reduced through co-treatment with
phenformin but not NAC. These "Cells treated with PA, however, were characterized by a negative net glycolytic rate since glutamine entry to the CAC was elevated relative to glucose."
"Detailed flux mapping with [U-13C5]glutamine revealed that palmitate treatment strongly increased CAC fluxes relative to glycolytic fluxes in H4IIEC3 cells. Changes in intracellular metabolic fluxes coincided with the onset of ROS accumulation and preceded the appearance of apoptotic markers such as caspase 3/7 activation and DNA laddering."
"These studies revealed that palmitate increased oxygen consumption and CAC fluxes independently of fatty acid beta-oxidation. Glutamine, rather than lipid, was the preferred substrate used to fuel palmitate-induced increases in mitochondrial metabolism."
In the past you've posted about the negative effects of glutamine uptake and use as a fuel;
"Some key points from the article that support Ray's views are that cancer cells rely on fermentation and especially glutamine. I think Ray wrote in one of his articles or books, that of all the amino acids tryptophan and glutamine are the most dangerous when taken separately or in high quantities. They are the most growth-promoting aminos for cancer cells." - Haidut, Cancer May Finally Start Getting Treated As Metabolic Issue
Ray has discussed the issue also on his site;
Cancer cells show all the signs of being intensely stimulated, and this includes a high
rate of oxygen consumption (deGroof, et al., 2009). The stimulation increases the
energy requirements beyond the ability of the mitochondria's capacity to meet them,
leading to the production of lactate even when a normal amount of oxygen is present.
Even when both glucose and oxygen are supplied (which they usually aren't), the tumor
cells will consume amino acids as fuel, as well as using them as material for growth.
Tumors have been called "nitrogen traps" or "glutamine traps," but this has meaning
beyond the use of the nitrogen for growth; it is involved in the energetic inefficiency of
this process, and the reorganizing effects this wasteful flow of energy has on the tissue
structure (Medina, 2001). When glutamine enters the Krebs cycle to be used as fuel,
this interferes with the ability to oxidize glucose, causing more lactic acid to be formed,
contributing to the excitation and increased energy requirement
- Ray Peat, Cancer: Disorder and Energy
Is it a good idea to increase cancer cells use of Glutamine?
That is a good point, but the palmitic acid incuded apopotosis in the hepatoma cells, not growth. So, despite this increase in glutamine consumption the overall effects were not negative. Cancer cells show deficiency of ROS production and palmitic acid strongly increased ROS. The amino acid NAC acted opposite to palmitate and cancer cells have a great appetite for antioxidants like NAC.