Four steps from α-ketoisovalerate, which is also the valine keto acid. Humans cannot do this
Route: α-Ketoisovalerate + Acetyl-CoA → (2S)-2-Isopropylmalate → (2R,3S)-3-Isopropylmalate → α-Ketoisocaproate → Leucine
Leucine is an essential amino acid for humans. The pathway starts from α-ketoisovalerate, which is also the valine keto acid. The first step adds the two carbons of an acetyl-CoA, the same kind of reaction as citrate synthase in the Krebs cycle. The second step moves the hydroxyl group one carbon along, through a dehydration and a rehydration at one iron-sulfur site. The third step oxidizes the new hydroxyl and releases CO₂, the same logic as isocitrate dehydrogenase. The last step is the transamination from glutamate.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | 2-Isopropylmalate synthase | 2.3.3.13 | H₂O | CoA-SH |
| 2 | 3-Isopropylmalate dehydratase | 4.2.1.33 | ||
| 3 | 3-Isopropylmalate dehydrogenase | 1.1.1.85 | NAD⁺ | NADH, CO₂ |
| 4 | Branched-chain aminotransferase | 2.6.1.42 | Glutamate | α-KG |
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).