title: Disturbances on delta aminolevulinate dehydratase (ALA-D) enzyme activity by Pb2+, Cd2+, Cu2+, Mg2+, Zn2+, Na+, K+ and Li+: analysis based on coordination geometry and acid-base Lewis capacity.
abstract: ALA-D (EC 4.2.1.24) is the first cytosolic enzyme in the haem metabolic pathway. Some metals compete with its major cofactor Zn(2+), modifying both enzyme structure and function. Our purpose was to contribute to the understanding of the biochemical role of metals such as Pb(2+), Cd(2+), Cu(2+), Mg(2+), Zn(2+), Na(+), K(+) and Li(+) on ALA-D, using chicken embryos as experimental model. Mg(2+) and Zn(2+) showed enzyme activation in yolk sac membrane (YSM) (113% at 10(-5) M Mg(2+) and from 10(-4) M Zn(2+)), and slight inactivation in liver. Cd(2+) and Cu(2+) caused a non allosteric inhibition in both tissues (100% from 10(-4) M). Surprisingly Pb(2+) was not such a strong inhibitor. Interference of cations during the Schiff base formation in enzymatic catalysis process is explained considering their Lewis acid-base capacity, coordination geometry and electron configuration of valence. Interactions among monovalent cations and biochemical substances are governed chiefly by its electrostatic potential. 0.1 M K(+) and 0.4 M Na(+) produced 30% of enzymatic inhibition by the interference on interactions among the functional subunits. Li(+) activated the YSM enzyme (130% at 10(-5) M) due to a more specific interaction. This study may contribute to elucidate for the first time the possible structural differences between the YSM and liver enzymes from chicken embryo.
authors.affiliation: Laboratorio de Porfirinas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II 1428, Capital Federal, Buenos Aires, Argentina.
authors.forename: N L
authors.initials: NL
authors.lastname: Pauza
authors.forename: M J Pérez
authors.initials: MJ
authors.lastname: Cotti
authors.forename: L
authors.initials: L
authors.lastname: Godar
authors.forename: A M
authors.initials: AM
authors.lastname: Ferramola de Sancovich
authors.forename: H A
authors.initials: HA
authors.lastname: Sancovich
mesh_terms: D000818:Animals; D002412:Cations / Q000494:pharmacology; D002642:Chick Embryo; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008670:Metals / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D012545:Schiff Bases / Q000737:chemistry; D015017:Yolk Sac / Q000201:enzymology
chemical_list: D002412:Cations; D004791:Enzyme Inhibitors; D008670:Metals; D012545:Schiff Bases; D000623:Porphobilinogen Synthase