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

ALA-D (EC 4.2.1.24) is the first cytosolic enzyme in the haem metabolic pathway. Some metals compete with its major cofactor Zn2+, modifying both enzyme structure and function. Our purpose was to contribute to the understanding of the biochemical role of metals such as Pb2+, Cd2+, Cu2+, Mg2+, Zn2+, Na+, K+ and Li+ on ALA-D, using chicken embryos as experimental model. Mg2+ and Zn2+ showed enzyme activation in yolk sac membrane (YSM) (113% at 10−5 M Mg2+ and from 10−4 M Zn2+), and slight inactivation in liver. Cd2+ and Cu2+ caused a non allosteric inhibition in both tissues (100% from 10−4 M). Surprisingly Pb2+ 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.