Glucose and glutamine inhibition during Cancerdialysis
Author: Sture Hobro
Cancer cells, and they have a huge demand for glucose, which they use to boost their survival. This increased glucose uptake is followed by an increased dependence on ATP production through fermentation. However, increased glycolysis also produces many substrates used to produce NADPH that can be used to boost survival by mitigating the increased oxidative stress that most cancer cells typically have.
Ketones are produced mainly from fat and are used as an excellent alternative energy fuel during starvation. They have been shown to have potential anti-cancerous effects, particularly in the context of epigenetic regulation. Epigenetic modifications are changes to the genome that do not involve changes in the DNA, and in contrast to DNA changes, epigenetic changes can be restored. One such change is HDAC1 overexpression, which cancer cells often have and impose immortality in cancer by inhibiting apoptosis signaling.
Ketones cannot be fermented like glucose for energy. They must be metabolized through the mitochondria for ATP production, and oxygen is needed for this process. Since the energy-producing functionality of mitochondria in cancer is compromised and oxygen availability is limited in cancer, increased reliance on ketones for ATP in cancer may affect cancer cells negatively. For example, counterintuitively, reduced oxygen leads to increased oxidative stress in cancer cells.
The figure shows how glucose will be reduced by different regimes. The Medical Ketogenic Diet (MKD) includes calorie restriction and 90% fat, 8% protein, and less than 2% carbohydrates and is known to be hard to follow. Besides glucose levels, glutamine and other amino acids will also be reduced during Cancer Dialysis and are unaffected during MKD. Glutamine is known to play a crucial role in cancer cell survival during glucose deprivation. A. Typical levels of glucose and ketones. B. Typical Glucose/ketone ratio during different regimes. C. Typical Glucose levels during different regimes.
