Figure 1
Biosynthetic pathways for BCAA. In the first reaction acetolactate synthase (ALS) condenses one pyruvate with another into 2-acetoacetate (for valine and leucine) or with 2-ketobutyrate to form 2-aceto-2-hydroxybutyrate (for isoleucine). Both products are then isomerized and reduced via keto-acid reductoisomerase (KARI) to form 2,3-dihydroxyisovalerate and 2,3-dihydroxy-3-methylvalerate, respectively. In this unusual two-step reaction, each substrate undergoes Mg2+-dependent alkyl migration followed by NAD(P)H-dependent reduction of the 2-keto group. Dihydroxyacid dehydratase (DHAD) converts two products of the second step to 2-ketoisovalerate and 2-keto-3-methylvalerate, respectively. The final step in the parallel pathway is conducted catalysed by amino transferase, which yields the final products of valine from 2-ketoisovalerate and isoleucine from 2-keto-3-methylvalerate. In contrast, a series of more additional enzymes are necessary to sequentially divert 2-ketoisovalerate to the leucine production pathway.
