D H Williamson1, Radcliffe Infirmary, Oxford, UK

© 2005 Elsevier Ltd. All rights reserved.

This article is a revision of the previous edition article by

D H Williamson, pp. 1160-1167, © 1999, Elsevier Ltd.

The two ketone bodies, acetoacetate (CH3COCH2COO~) and D-3-hydroxybutyrate (CH3CHOHCH2COO~), are the only freely soluble lipids in the circulation.

The name ketone bodies originates from the German Ketonkorper (literally, ketones excreted from the body) and refers to their discovery in the urine of diabetic patients in the latter half of the nineteenth century. In reality, the term is a misnomer because 3-hydroxybutyrate is not a ketone. It arose because the reagent originally used reacted positively with ketones in diabetic urine. Acetone (CH3COCH3), the product of the spontaneous decarboxylation of acetoacetate, is also a ketone and is present in blood and urine when the plasma concentration of acetoacetate is elevated. It is excreted via the kidneys and lungs and is responsible for the sweet smell on the breath in ketotic states.

The association of ketone bodies with the pathology of diabetes resulted in the view that they were toxic waste products. It is only in the past 30 years that this view has been convincingly reversed. Two factors led to this change, namely the development of an enzymatic method for the determination of acetoacetate and 3-hydroxybutyrate, which in turn allowed the dramatic finding of Cahill and colleagues in 1967 that adult human brain removed appreciable amounts of ketone bodies from the circulation in prolonged starvation.


The aim in this contribution is to review (a) the formation of ketone bodies in physiological and pathological situations, and (b) the function of ketone bodies as physiological substrates and signals.

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