What is ketosis? What is the science?
What is ketosis?
Ketosis is simply an alternative fuel supply for the body and the brain. It is a metabolic state in which much of the body’s energy supply comes from ketone bodies and fat oxidation rather than glucose.
Energy demands of the cell
The cells in your body require energy for three types of tasks: transporting needed substances across membranes, driving metabolic reactions that don’t occur automatically and to do mechanical work like contracting muscles. Carbohydrates and fats store chemical energy. When that energy is needed by the cell, those carbs and fats are converted into ATP (Adenosine triphosphate). From there, ATP acts as a transporter for that energy to certain areas in the cell that need it.
The Krebs Cycle (Citric Acid Cycle)
If you consume carbohydrates, your body goes through a process call glycolysis to convert glucose (from carbohydrates) into pyruvate. This conversion process generates ATP molecules.
Under normal conditions, fatty acids are broken down in beta-oxidation and glucose is broken down in glycolysis to form acetyl-CoA. This acetyl-CoA then goes through several enzymic reactions in the Krebs cycle to create ATP through a process called oxidative phosphorylation. That is a totally normal process that occurs in everyone.
The Blood Brain Barrier (BBB)
In the absence of carbohydrates, your body is going to look for an alternative fuel supply to power the body and brain. However, you can’t simply turn to fat alone as the next available energy source due to the Blood Brain Barrier (BBB). The BBB is a semi-permeable layer surrounding your brain formed by endothelial cells that fit tightly together. This barrier acts as a protective mechanism preventing foreign substances from entering the brain. However, it also prevents fatty acids from entering the brain as an energy source. To combat this, our body produces ketones that are able to cross the BBB and provide energy to the central nervous system.
Without Carbohydrates | Gluconeogenesis
Without carbs, glucose and insulin levels drop and your body needs an increased amount of enzymes to synthesize energy molecules. Glucagon is a regulatory hormone that acts as the inverse of insulin and is released when blood glucose levels are low. Glucagon triggers gluconeogenesis which is the production of glucose from non-carbohydrate substances like muscle tissue.
That is all fine and dandy for awhile but continued gluconeogenesis is going to have a serious catabolic effect on muscle tissue which is not ideal. Gluconeogenesis also results in the depletion of oxaloacetic acid which is a metabolic intermediate necessary for the oxidation of acetyl CoA in the Krebs cycle. Without an ample supply of Oxaloacetate, acetyl-CoA can’t efficiently produce ATP using the Krebs cycle and is shunted towards ketone body production. The acetyl-CoA undergoes a biosynthesis process in the liver that generates ketone bodies via thiolase, acetoacetyl-CoA, and beta-hydroxy-beta-methylglutaryl-CoA. This multi-step, enzyme-catalyzed process results in the production of the ketone body acetoacetate. A fourth enzyme, beta-hydroxybutyrate dehydrogenase, then reduces acetoacetate to beta-hydroxybutyrate.
Ketone Bodies For Energy
Both acetoacetate and beta-hydroxybutyrate are then released into the bloodstream and used by the body in place of glucose. The beta-hydroxybutyrate molecule is more stable than the acetoacetate which is why it’s predominately used for transportation. Acetoacetate is a beta-ketoacid and may spontaneously decarboxylate. The byproduct of this decarboxylation reaction is acetone which is excreted in the breath.
Once the ketone bodies reach the cells in need, they go through a process called ketolysis. Ketolysis is the conversion of ketone bodies back into acetyl-CoA which then feeds into the aforementioned Krebs cycle for the mitochondrial generation of ATP.
- Ward, Colin. Ketone body metabolism [internet]. 2015 Nov 18; Diapedia 51040851169 rev. no. 29. Available from: https://doi.org/10.14496/dia.51040851169.29
- Schönfeld P, Reiser G. Why does brain metabolism not favor burning of fatty acids to provide energy? - Reflections on disadvantages of the use of free fatty acids as fuel for brain. Journal of Cerebral Blood Flow & Metabolism. 2013;33(10):1493-1499. doi:10.1038/jcbfm.2013.128.
- Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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