Ketone Bodies


Ketone bodies are water‐soluble equivalents of fatty acids. They can substitute for glucose in peripheral tissues, especially in the brain, when glucose becomes limited in physiological and pathological states. Recent findings demonstrate that they also act as signalling metabolites, thus participating in the organism adaptation to the environment, such as during fasting, calorie restriction or prolonged exercise. Diabetes is the most common pathological cause of elevated blood ketone bodies. Ketone bodies are produced in excess in response to low insulin levels and high levels of counterregulatory hormones, the result being the development of metabolic acidosis that is associated with serious health complications. Yet, ketogenic diets have been used for decades to increase ketone body synthesis for their neuroprotective properties as central signalling metabolites and as main energy‐providing substrate for the brain, in epilepsy and neurodegenerative diseases.

Key Concepts

  • Ketone bodies are key energy substrates and signalling molecules
  • Ketone bodies participate in energy homeostasis
  • Diabetic ketoacidosis is the most common pathological cause of elevated blood ketone bodies and is associated with serious health complications
  • Ketone bodies are neuroprotective
  • Ketone bodies offer promising perspectives in clinical therapy for certain metabolic diseases, neurodegenerative diseases and cancers

Keywords: ketone bodies; energy homeostasis; starvation; exercise; ketoacidosis; neuroprotection

Figure 1. The synthesis of acetoacetate and d‐β‐hydroxybutyrate from acetyl‐CoA in the liver mitochondria.
Figure 2. The metabolic conversion of d‐β‐hydroxybutyrate and acetoacetate to acetyl‐CoA in the mitochondria of peripheral tissues.
Figure 3. Inhibition of the glycolytic pathway by ketone body oxidation. Oxidation of ketone bodies causes acetyl‐CoA and NADH to increase in the mitochondria, thereby inhibiting pyruvate dehydrogenase activity, and thus pyruvate oxidation. As part of the feedback loop, the glycolytic pathway is ultimately inhibited by an increased concentration of citrate and glycolytic intermediates.
Figure 4. Schematic summary of ketone body production, accumulation, utilisation and metabolic effects.


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Morio, Beatrice, and Wolfe, Robert R(Apr 2015) Ketone Bodies. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003819.pub2]