Ketone Bodies – Definition

Ketone bodies are water soluble compounds containing ketone groups that are produced in the liver during caloric restrictions in the body. The process of formation of ketone bodies in the liver is referred to as ketogenesis. These molecules are released to act as an energy source in the absence of glucose.

The three molecules that are referred to as ketone bodies are acetoacetate (AcAc), acetone and 3-β-hydroxybutyrate (3HB).

Why are Ketone Bodies Produced?

The ketone bodies are produced under circumstances such as prolonged fasting, intense exercise, starvation, diets restricted in carbohydrates, alcoholism and untreated conditions of type I diabetes mellitus, basically at times when the blood glucose level is low. In these conditions, first the glycogen storage is broken down to be used in the form of energy. But soon, the liver runs out of the glycogen storage and as a last resort the fatty acids are broken down to ketone bodies.

The ketone bodies are then transported out of the liver and converted into acetyl coenzyme A (acetyl-CoA). The acetyl-CoA then enters the Krebs cycle to be oxidised for energy.

Acetoacetate is formed by the fusion of two acetyl coenzyme A molecules by forming a dimer after losing the -CoAs. 3-β-hydroxybutyrate is formed by the reduction of acetoacetate and acetone is the decarboxylated form of acetoacetate. AcAc and 3HB are predominantly involved in the transport of energy from liver to other tissues. Acetone on the other hand, is the spontaneous product of decarboxylation of AcAc and gives a distinguishing sweet breath to the person undergoing ketoacidosis.

How are Ketone Bodies Produced?

As stated above, the formation of ketone bodies is referred to as ketogenesis. When our diet is restricted of glucose, the insulin level is low and the epinephrine and glucagon levels are high, this stimulates the release of fatty acids from the adipose tissues. The fats stored in the adipose tissues are released in the form of free fatty acids and glycerol.

These fat cells are taken up in the mitochondria of liver cells (hepatocytes). The fatty acids are combined with coenzyme A by the process of β-oxidation to form acetyl-CoA. The acetyl-CoA is converted to acetoacetyl-CoA and then into 3-hydroxy-3-methylglutaryl CoA (HMG CoA). Finally, the HMG-CoA is converted to AcAc and then reduced to 3-HB.

AcAc and 3-HB are 4-carbon short chain organic acids that can freely diffuse across membranes and are used up in the form of energy.

Ketone Body Levels

A basic level of ketone is always maintained in our blood, however it varies according to age, basal metabolic rate and hepatic glycogen storage. The postprandial level of circulating ketone body ranges <50μM, whereas normal serum levels can be <0.5mM. The ratio of 3-HB to AcAc (known as ketone body ratio) is usually 1 after a satiated meal but can rise up to 6 after prolonged fasting.

How are Ketone Bodies used as a Fuel?

The ketone bodies can be taken up by heart, muscles and brain, but not the liver itself because it lacks the enzyme that breaks the ketone bodies. Upon oxidation in mitochondria, AcAc can release two molecules of GTP and 22 molecules of ATP. Acetone, on the other hand, is taken up by the liver in low concentrations and metabolised using a different pathway.

Brain: The brain cannot take up the fatty acids directly to utilise it in the form of energy. Therefore during the times of compromised glucose levels in blood, ketone bodies supply up to two-thirds of the energy required for proper functioning of the brain.

Heart: Under normal physiological conditions, the heart prefers to utilise fatty acids directly for their source of energy. However under low glucose conditions, it can take up ketone bodies as well.

Ketosis

Ketone bodies are produced constantly in our bodies but are utilised by the extrahepatic tissues continuously and hence cannot be traced. However, when the level of production exceeds the level of utilisation, it creates a condition called ketonemia which is the increased level of ketones in blood. This also leads to ketonuria which is the excretion of ketone bodies in urine. Both these conditions together are referred to as ketosis and the primary symptom of identification is the sweet smell of acetone in one’s breath.

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