Acetyl-CoA to acetoacetate and D-3-hydroxybutyrate, the fuels the liver supplies to other tissues
Route: Acetyl-CoA → Acetoacetyl-CoA → 3-Hydroxy-3-methylglutaryl-CoA → Acetoacetate → D-3-Hydroxybutyrate
Thiolase joins two acetyl-CoA into acetoacetyl-CoA and releases one CoA. HMG-CoA synthase adds a third acetyl-CoA and gives HMG-CoA, a six-carbon compound with a hydroxyl and a methyl group on the same carbon. HMG-CoA lyase cuts it back into acetyl-CoA and acetoacetate, so the net result of the three steps is one acetoacetate from two acetyl-CoA. D-3-Hydroxybutyrate dehydrogenase reduces acetoacetate with NADH to D-3-hydroxybutyrate. In humans the liver makes ketone bodies in the mitochondrial matrix, mostly when fatty acid breakdown supplies more acetyl-CoA than the Krebs cycle takes up, for example during fasting. Acetoacetate also loses CO₂ slowly by itself and gives acetone, which was left out here. Other tissues turn the ketone bodies back into acetyl-CoA to burn them. HMG-CoA is also the start of the mevalonate pathway, which uses a separate synthase in the cytosol.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Acetyl-CoA acetyltransferase (thiolase) | 2.3.1.9 | Acetyl-CoA | CoA-SH |
| 2 | Hydroxymethylglutaryl-CoA synthase | 2.3.3.10 | Acetyl-CoA, H₂O | CoA-SH |
| 3 | Hydroxymethylglutaryl-CoA lyase | 4.1.3.4 | Acetyl-CoA | |
| 4 | D-3-Hydroxybutyrate dehydrogenase | 1.1.1.30 | NADH | NAD⁺ |
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).