Ketone Bodies

Ketone Bodies

Synthesized from acetyl CoA in liver mitochondria and secreted into the blood for use as fuel by some tissues such as heart muscle:

• Acetoacetate

• D-3-beta-hydroxybutyrate

• Acetone

Carried from the liver mitochondria into the blood by transport proteins and are conveyed to other tissues such as heart and kidney

D-3-beta-hydroxybutyrate

formed upon the reduction of acetoacetate

Acetone

generated by the spontaneous decarboxylation of acetoacetate

In tissues using ketone bodies:

D-3-beta-hydroxybutyrate is oxidized to acetoacetate, which is ultimately metabolized to two molecules of acetyl CoA.

When acetyl-CoA builds up:

there will be a shift to produce ketone bodies in the liver mitochondria

Acetoacetate and D-3-hydroxybutyrate

Known to be normal fuels of respiration:

• They are not just indicators of impaired metabolism

• They are important sources of energy

Heart Muscle and the Renal Cortex

use acetoacetate in preference to glucose

The Brain

adapts to the utilization of acetoacetate during starvation and diabetes

In Prolonged Starvation:

75% of the fuel needs of the brain are met by ketone bodies

Ketogenic Diets

Diets that promote ketone-body formation:

• They are rich in fats, low in carbohydrates, and have adequate amounts of protein

• The body is forced into starvation mode, where fats and ketone bodies become the main fuel source

Ketogenic diets have been used as therapy:

• They were first used to treat GLUT1 Deficiency Syndrome, a rare epileptic disease that impairs glucose transport to the brain.

• They are now also frequently used as a therapeutic option for children with drug- resistant epilepsy of other causes.

• Research in mice suggests that ketogenic diets alter the intestinal flora, and it is this alteration in the microbiome that is responsible for the diet’s therapeutic effects.