Ketone metabolism · Grey Matter

Ketone metabolism is the brain's use of ketone bodies, small fuels made by the liver from fat, in place of part of its glucose, and it is what lets the brain keep working through days and weeks of fasting.

Ketone metabolism. Ketone metabolism is the brain's use of ketone bodies, small fuels made by the liver from fat, in place of part of its glucose, and it is what lets the brain keep working through days and weeks of fasting.

When carbohydrate is scarce, the liver turns fatty acids into acetoacetate and beta-hydroxybutyrate and releases them into the blood. They cross the blood-brain barrier on monocarboxylate transporters, and neurons and glia convert them to acetyl-CoA, which enters the citric acid cycle and oxidative phosphorylation like the products of glucose. How much the brain uses depends on how high blood ketones rise: little after an overnight fast, and after five to six weeks of starvation, in the classic measurements of Owen and colleagues (1967), ketones supplied about 60 % of the brain's energy, up to about two thirds.

It spares the body's protein. The brain cannot burn fatty acids directly at any useful rate; without ketones, prolonged fasting would require breaking down muscle protein to make glucose for it.

Glucose remains necessary. Some cells and pathways still need glucose, so even in deep ketosis the brain takes a reduced but steady glucose supply.

Diets that raise ketones are used as a treatment. The ketogenic diet reduces seizures in some drug-resistant epilepsies; how it works (fuel change, effects on transmitters, channels or inflammation) is still debated.

Ketones are the brain's emergency fuel line from fat.

They let a glucose-hungry organ survive long fasts without consuming the body's muscle to feed it.

Questions: What does the brain run on during a long fast? At first on glucose, released from the liver's glycogen and then made from amino acids and glycerol. As the fast continues, the liver converts fat into ketone bodies (beta-hydroxybutyrate and acetoacetate), their blood level rises, and the brain takes them up and burns them in its mitochondria. In the classic measurements of Owen and colleagues (1967), after five to six weeks of starvation ketones supplied about 60 % of the brain's energy, and up to about two thirds by other estimates. This spares muscle protein that would otherwise be broken down to make glucose, while the brain keeps a smaller but necessary glucose supply.