2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit delta-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 delta-aminolevulinate dehydratase (delta-ALA-D) from human erythrocytes were evaluated. Furthermore, possible protective effects of zinc chloride (ZnCl(2)), dithiothreitol (DTT), and cysteine were studied. delta-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 delta-ALA-D. Zinc chloride at 500 microM 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 delta-ALA-D inhibitor of human erythrocytes. These data are in agreement with delta-ALA-D activity from purified enzyme. ZnCl(2) (1 microM) added, in the reaction mixture, increased enzyme activity and DTT (100 microM) totally restored the enzyme activity for all chelating agents tested.
Nogueira
C W
CW
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. criswn@quimica.ufsm.br
Santos
F W
FW
Soares
F A
FA
Rocha
J B T
JB
D002614:Chelating Agents / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004112:Dimercaprol / Q000494:pharmacology*; D004229:Dithiothreitol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019163:Reducing Agents / Q000378:metabolism; D004113:Succimer / Q000494:pharmacology*; D014494:Unithiol / Q000494:pharmacology*; D017967:Zinc Compounds / Q000378:metabolism
D002614:Chelating Agents; D002712:Chlorides; D019163:Reducing Agents; D017967:Zinc Compounds; D004112:Dimercaprol; D014494:Unithiol; C016837:zinc chloride; D004113:Succimer; D000623:Porphobilinogen Synthase; D003545:Cysteine; D004229:Dithiothreitol