<p>The branched-chain amino acids are synthesised by a common pathway that leads from pyruvate and alpha-ketobutyrate to valine and isoleucine, and a branch that leads from the immediate precursor of valine, alpha-ketoisovalerate, to leucine [<cite idref="PUB00034699"/>]. This pathway operates in archaea, bacteria, fungi and plants, but not mammals, making the enzymes suitable targets for the development of novel antibiotics and herbicides.</p><p>Isopropylmalate synthase is the enzyme responsible for the the first committed step in the leucine branch of this biosynthetic pathway, the conversion of alpha-ketoisovalerate to alpha-isopropylmalate. It is either dimeric or tetrameric, depending on the organism, with a monomer molecular mass of 60-70 kDa, a dependence on divalent metal ions for activity, and an alkaline pH optimum [<cite idref="PUB00034700"/>, <cite idref="PUB00034701"/>, <cite idref="PUB00034702"/>, <cite idref="PUB00020847"/>]. Like many other biosynthetic enzymes it is subject to feedback inhibition by the end product of the pathway, leucine. </p><p>This entry represents the isopropylmalate synthase most commonly found in bacteria. A related form of this enzyme is found mainly in eukaryotes and some other bacteria (<db_xref db="INTERPRO" dbkey="IPR005668"/>). A homologous family in archaea may represent isozymes and/or related enzymes (<db_xref db="INTERPRO" dbkey="IPR005675"/>).</p>