The leucine synthesis pathway diverges from the valine pathway beginning with α-ketoisovalerate. α-Isopropylmalate synthase catalyzes this condensation with acetyl CoA to produce α-isopropylmalate. An isomerase converts α-isopropylmalate to β-isopropylmalate. The third step is the NAD-dependent oxidation of β-isopropylmalate catalyzed by a dehydrogenase. The final step is the transamination of the α-ketoisocaproate by the action of a glutamate-leucine transaminase.
Leucine, like valine, regulates the first step of its pathway by inhibiting the action of the α-Isopropylmalate synthase. Because leucine is synthesized by a diversion from the valine synthetic pathway, the feedback inhibition of valine on its pathway also can inhibit the synthesis of leucine.