2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase mercury- and cadmium-induced inhibition of δ-aminolevulinate dehydratase

Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propane-1-sulfonic acid (DMPS), are becoming common agents for treating humans exposed to heavy metals. Heavy metals such as Pb2+, Hg2+ and Cd2+ can inhibit delta-aminolevulinate dehydratase (delta-ALA-D) activity. delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor. The effects of DMSA and DMPS alone or in combination with Cd2+, Hg2+, or Pb2+ on hepatic delta-ALA-D were examined. DMPS and DMSA caused a dose-dependent inhibition of hepatic delta-ALA-D. In the presence of Hg2+ or Cd2+ the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of Hg2+ and Cd2+ were markedly increased in the presence of DMSA. In contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb2+. As observed with DMSA, Zn2+ did not modified the inhibitory effect of DMPS. Data of the present report support the idea that the complexes formed (metals-DMSA or DMPS) were more inhibitory than the metal (Hg2+ and Cd2+)or the chelating agent alone to the hepatic delta-ALA-D activity, in vitro. The mechanism of hepatic delta-ALA-D inhibition by Hg2+-DMPS/DMSA and Cd2+-DMPS/DMSA complexes involve the essential thiol groups of the enzyme. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.