2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit δ-aminolevulinate dehydratase from human erythrocytes in vitro
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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 4mM DMPS and DMSA, but protected 1mM BAL inhibition. Dithiotreitol was able to protect the inhibition caused by 1mM BAL (28 % ), DMPS (56 % ), and DMSA (40 % ) in a concentration-dependent manner. Zinc chloride protected and restored 1mM BAL inhibitory effect on δ-ALA-D. Zinc chloride at 500μM and 1mM, respectively, protected inhibitory effects of DMPS and DMSA (1 and 4mM), 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 (1μM) added, in the reaction mixture, increased enzyme activity and DTT (100μM) totally restored the enzyme activity for all chelating agents tested.

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