The Role of Dehydroalanine in Catalysis by Histidine Ammonia Lyase

摘要

The conversion of L-histidine into urocanic acid, catalyzed by histidine ammonia lyase (HAL), is an unusual elimination reaction and poses a mechanistic challenge for chemists. The step-wise and the concerted reaction modes either lead to unlikely, energetically disfavored intermediates or are based on implausible assumptions, HAL catalyzes the first step in histidine degradation in most organisms, and its failure in humans causes his-tidinemia. HAL and the important plant enzyme phenylala-nine ammonia lyase are the only enzymes known to contain a catalytic-ally essential dehydroalanine, which has been shown to arise posttranslationally from serine 143 and ser-ine 202, respectively. Because of the electrophilicity of this prosthetic group it has been suggested that the a-amino group of histidine attacks it as a nucleophile thus enhancing the leaving ability of the amino group.