Metabolic shift during CancerDialysis
Author: Sture Hobro
When starving or eating a ketogenic diet and moving into ketosis, the substrate used for ATP generation will shift from primarily glucose in a normal state to ketones during ketogenic condition. This shift is known to occur as an effect of starvation or during eating a ketogenic diet.
During normal feeding conditions, 50-60% of the energy supplied to cells comes from glucose (>200 gram).
During fasting, energy metabolism will gradually shift towards ketosis. In this picture, we refer to light ketosis as what you achieve after approximately 2-4 days of fasting, while deep ketosis is achieved after weeks of starvation. Some glucose will always be produced through gluconeogenesis during ketosis, and even in deep ketosis, roughly 70 grams of glucose will be produced through gluconeogenesis per day.
CancerDialysis will be able to reduce approximately half of the 70 grams of glucose produced during deep ketosis, and total glucose contribution to the total energy expenditure will be reduced to less than 10%. During CancerDialysis we will support the liver to produce ketones either with exogenous ketones or appropriate fuels.
Glucose is a primary source of energy for cells during normal feeding conditions, including cancer cells. During normal feeding conditions, approximately 50-60% of the energy supplied to cells comes from glucose. Cancer depends on glucose for their survival and proliferation.
Glutamine, the most abundant amino acid in the blood, is also essential for cancer cells. Healthy cells and cancer cells both need glutamine to survive, but this dependency is increased in cancer cells and even more pronounced when glucose availability is decreased. Understanding the importance of glucose and glutamine in cancer metabolism is crucial for developing new therapies to block cancer metabolism without affecting normal healthy cells.
Ketones plays a crucial role in cellular metabolism and are particularly important in situations where glucose availability is limited, as during starvation and eating a ketogenic diet. Ketones can be used as an energy source by all tissues, including the brain. However, ketones must be metabolized in cells through the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) utilizing oxygen and can’t be fermented for ATP in cancer cells nor can ketones contribute to the vast metabolic system that glycolysis and glutaminolysis is, e.g. and cant provides access to the numerous metabolites present in the metabolic system feed by glucose and glutamine that are important for cancer survival.
The figure shows that the source (substrate) used for energy consumption could change during different metabolic stages. During CancerDialysis, roughly half of the glucose produced by gluconeogenesis during a ketogenic condition will be removed by dialysis.
