Model Construction and Analysis of Ketone Body Metabolism in the Brain

The brain is a highly metabolic organ which requires a continuous supply of energy to satisfy the demand of its constituent cells. Under normal conditions, it derives its energy exclusively from the oxidation of glucose. However, under specific physiological conditions such as fasting/starvation or prolonged exercise, when glucose is scarce, ketone bodies (KBs) have shown to act as an alternative cerebral fuel. The synthesis of KBs (called ＂ketogenesis＂) occurs primarily in hepatocytes (liver cells), from where they enter the bloodstream and are taken up for utilization (called ＂ketolysis＂) by various organs, including the brain. It has also been shown (in vitro) that astrocytes are capable of ketogenesis in a strikingly similar capacity as hepatocytes. Though the biochemistry of KBs has been extensively studied, there is still no existing mathematical model of ketone body metabolism in the brain. In this study, we constructed a mathematical model of ketone body metabolism in the brain using Biochemical Systems Theory (BST). The model was validated using existing data from scientific journals. Stability and sensitivity analyses of the model were also done. This research attempts to contribute in a much complex model of brain energy metabolism which investigates the potential role of ketone bodies in treating AD.