2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit δ-aminolevulinate dehydratase from human erythrocytes in vitro

The effects of dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonic acid (DMPS), and 2,3-dimercaptopropanol (BAL) on δ-aminolevulinate dehydratase (δ-ALA-D) from human erythrocytes were evaluated. Furthermore, possible protective effects of zinc chloride (ZnCl2), dithiothreitol (DTT), and cysteine were studied. δ-ALA-D activity from human erythrocytes was inhibited by dithiol chelating agents in a concentration-dependent manner. Cysteine, at all concentrations tested, did not protect the inhibitory effect of 1 and 4 mM DMPS and DMSA, but protected 1 mM BAL inhibition. Dithiotreitol was able to protect the inhibition caused by 1 mM BAL (28%), DMPS (56%), and DMSA (40%) in a concentration-dependent manner. Zinc chloride protected and restored 1 mM BAL inhibitory effect on δ-ALA-D. Zinc chloride at 500 μM and 1 mM, respectively, protected inhibitory effects of DMPS and DMSA (1 and 4 mM), but did not reverse its effects. The preincubation of dithiol chelating agents with enzyme demonstrated that DMSA was the most potent δ-ALA-D inhibitor of human erythrocytes. These data are in agreement with δ-ALA-D activity from purified enzyme. ZnCl2 (1 μM) added, in the reaction mixture, increased enzyme activity and DTT (100 μM) totally restored the enzyme activity for all chelating agents tested.