Download INTERACTION OF METALS FROM GROUP 10 (Ni(II), Pd(II

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23 Congress of the International Union for Biochemistry and Molecular Biology
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44 Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology
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Foz do Iguaçu, PR, Brazil, August 24 to 28 , 2015
INTERACTION OF METALS FROM GROUP 10 (Ni(II), Pd(II), Pt(II), AND Pt(IV))
AND 11 (Cu(II), Ag(I) E Au(III)) WITH δ-ALA-D OF HUMAN BLOOD: AN IN VITRO
AND IN SILICO STUDY.
BREMM, J. M.1; KLIMACZEWSKI, C. V.1; PICCOLI, B.1; SOARES, J. O.1; BRAGA,
M. M.1; NOGARA P.2; BARBOSA, N. V.1.
1
Department of Biochemistry and Molecular Biology and Program of PostGraduation in Biological Sciences-Biochemical Toxicology, Federal University of
Santa Maria, Camobi Campus, Santa Maria, RS 97105-900, Brazil
2
Department of Organic Chemistry, Federal University of Santa Maria, Camobi
Campus, Santa Maria, RS 97105-900, Brazil
Introduction and Goals: The mammalian δ-aminolevulinate dehydratase (δ-ALAD) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for maximal
catalytic activity. This enzyme is an important molecular target of toxic metals. The
inhibitory mechanism on δ-ALA-D activity by elements from Group 10, nickel
(NiCl2), palladium (PdCl2), platinum (PtCl2 and PtCl4) and 11, copper (CuSO4),
silver (AgNO3), gold (AuCl3) of periodic table has not yet been determined. Here,
we characterized the molecular mechanism of δ-ALA-D inhibition caused by salts
of elements from Group 10 and 11 of periodic table.
Materials and methods: The δ-ALA-D activity from human erythrocytes was
determined with or without metals. The in silico approaches were determined by
geometry optimization via PM6 method from MOPAC20122 software and via PBE
method from DMOL3 software.
Results and conclusion: The in vitro analysis showed that Ni(II) and Pd(II)
caused only a weak inhibition (~10%) in the δ-ALA-D activity, and this inhibition
was attenuated by Zn(II). Both Pt(II) and Pt(IV) did inhibit substantially the δ-ALAD activity (75% and 44%, respectively), but these effects were mitigated by Zn(II)
and DTT. In Group 11, all metals caused a significant in vitro inhibition in δ-ALA-D
activity (100%), and the simultaneous incubation with DTT did block the inhibition
caused by metals from Group 11. The in silico analisys on interaction of metals
and δ-ALA-D active site indicated that metals from Group 10 tended to compete
with Zn(II) of δ-ALA-D, and the metals from Group 11 seemed interact with thiol
groups of enzyme active site. The results obtained by in vitro and in silico
approaches suggest that the heavier metals from Group 10 tended to compete
with Zn(II) for the oxidation of thiols, and metals from Group 11 seemed to perform
a inhibitory mechanism related to the oxidation of thiol groups of the active site of
enzyme.
Acknowledgements: CNPQ and CAPES.
Keywords: δ-aminolevulinate dehydratase, Heavy metals, Enzymatic activity.
Brazilian Society for Biochemistry and
Molecular Biology (SBBq)