title: Evolution of the biosynthesis of the branched-chain amino acids.
abstract: The origin of the biosynthetic pathways for the branched-chain amino acids cannot be understood in terms of the backwards development of the present acetolactate pathway because it contains unstable intermediates.  We propose that the first biosynthesis of the branched-chain amino acids was by the reductive carboxylation of short branched chain fatty acids giving keto acids which were then transaminated.  Similar reaction sequences mediated by nonspecific enzymes would produce serine and threonine from the abundant prebiotic compounds glycolic and lactic acids.  The aromatic amino acids may also have first been synthesized in this way, e.g. tryptophan from indole acetic acid.  The next step would have been the biosynthesis of leucine from alpha-ketoisovaleric acid.  The acetolactate pathway developed subsequently.  The first version of the Krebs cycle, which was used for amino acid biosynthesis, would have been assembled by making use of the reductive carboxylation and leucine biosynthesis enzymes, and completed with the development of a single new enzyme, succinate dehydrogenase.  This evolutionary scheme suggests that there may be limitations to inferring the origins of metabolism by a simple back extrapolation of current pathways.
authors.affiliation: Department of Chemistry, University of California San Diego, La Jolla 92093-0317, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Keefe
authors.forename: A
authors.initials: A
authors.lastname: Lazcano
authors.forename: S L
authors.initials: SL
authors.lastname: Miller
mesh_terms: D000095:Acetolactate Synthase / Q000737:chemistry / Q000378:metabolism; D000596:Amino Acids / Q000096:biosynthesis*; D001419:Bacteria; D002952:Citric Acid Cycle; D003653:Decarboxylation; D019418:Evolution, Chemical; D005232:Fatty Acids, Volatile / Q000378:metabolism; D007532:Isoleucine / Q000096:biosynthesis* / Q000737:chemistry; D007930:Leucine / Q000096:biosynthesis* / Q000737:chemistry; D014633:Valine / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D000596:Amino Acids; D005232:Fatty Acids, Volatile; D007532:Isoleucine; D000095:Acetolactate Synthase; D007930:Leucine; D014633:Valine