EVOLUTION OF THE BIOSYNTHESIS OF THE BRANCHED-CHAIN AMINO-ACIDS

The origin of the biosynthetic pathways for the branched-chain amino a cids cannot be understood in terms of the backwards development of the present acetolactate pathway because it contains unstable intermediat es. We propose that the first biosynthesis of the branched-chain amino acids was by the reductive carboxylation of short branched chain fatt y acids giving keto acids which were then transaminated. Similar react ion sequences mediated by nonspecific enzymes would produce serine and threonine from the abundant prebiotic compounds glycolic and lactic a cids. The aromatic amino acids may also have first been synthesized in this way, e.g. tryptophan from indole acetic acid. The next step woul d have been the biosynthesis of leucine from alpha-ketoisovaleric acid . The acetolactate pathway developed subsequently. The first version o f the Krebs cycle, which was used for amino acid biosynthesis, would h ave been assembled by making use of the reductive carboxylation and le ucine biosynthesis enzymes, and completed with the development of a si ngle new enzyme, succinate dehydrogenase. This evolutionary scheme sug gests that there may be limitations to inferring the origins of metabo lism by a simple back extrapolation of current pathways.