Reactome: A Curated Pathway Database

Synthesis of Ketone Bodies (R-HSA-77111)

Species Homo sapiens


In a healthy, well-nourished individual, the production of ketone bodies occurs at a relatively low rate. During periods of normal physiological responses to carbohydrate shortages, the liver increases the production of ketone bodies from acetyl-CoA generated from fatty acid oxidation. This allows heart and skeletal muscle to use ketone bodies as the primary source of energy, thereby preserving the limited glucose supply for use in brain tissue.

In untreated diabetes mellitus, a huge buildup of ketone bodies occurs due to an increase in fatty acid oxidation. The production of ketone bodies exceeds the ability of peripheral tissues to oxidize them, and results in lowering the pH of blood. Blood acidification is dangerous, chiefly as it impairs the ability of hemoglobin to bind oxygen.

Ketone body synthesis proceeds via the synthesis of ccetoacetic acid in three steps from acetyl CoA, followed by the reduction of acetoacetic acid to beta-hydroxybutyrate. In the body, these reactions occur in the mitochondria of liver cells (Sass 2011).

Locations in the PathwayBrowser
Additional Information
Compartment mitochondrial matrix
GO Biological Process ketone body biosynthetic process (0046951)
Literature References
pubMedId Title Journal Year
21479626 Inborn errors of ketogenesis and ketone body utilization J Inherit Metab Dis 2011