Interaction of analogues of porphobilinogen with porphobilinogen deaminase

Abstract

2-Methylporphobilinogen 5 and 8,9-didehydroporphobilinogen 7 are only weak inhibitors of porphobilinogen deaminase (hydroxymethylbilane synthase). The phosphonate analogue 8 and 9-fluoroporphobilinogen 9 are good inhibitors, however, and also act as slow substrates (the first unnatural substrates known for this enzyme). The particularly strong inhibition shown by the fluoro analogue 9 is shown to be due to the slow regeneration of free enzyme once the compound has become covalently bound to it. This results in a sigmoidal dependence of rate vs.[substrate].