Mechanism-based inactivation of porphobilinogen synthase: Substitution of ketone functionality in the substrate with a thioester

The thioester (5) was found to inactivate the enzyme porphobilinogen synthase. Replacement of the ketone functionality in aminolevulinic acid (ALA), shown to be involved in Schiff-base linkage with an active site lysine residue, by a thioester moiety was found to result in loss of enzyme activity. A plausible mode of inactivation is proposed.