Evolutionary constraints in the mechanism of flavin catalysis

Analysis of the possible evolution of flavin catalysis in succinate dehydrogenase suggests as the ultimate state an active site that bears one or more acid functions and uses the enediol form of the substrate rather than the carbanion as a nucleophile. In the case of flavoenzyme catalyzed oxidation of fatty acylCoA, alpha-amino acids and alpha-hydroxy acids evolution to a similar mechanism seems to be blocked.