A COMPARISON OF THE EFFECTS OF INORGANIC AND ALKYLLEAD COMPOUNDS ON HUMAN ERYTHROCYTIC DELTA-AMINOLEVULINIC-ACID DEHYDRATASE (ALAD) ACTIVITY INVITRO

A study comprising two experiments comparing the effects of the alkyllead compounds triethyllead acetate and tetraethyllead as well as an inorganic lead compound (Pb(NO3)2) on human erythrocytic delta-aminolevulinic acid dehydratase activity was undertaken. In Experiment 1, four human blood samples were pre-incubated for 0 min or 60 min with increasing concentrations (0-1000-mu-M) of triethyllead acetate, tetraethyllead and Pb(NO3)2, and the delta-aminolevulinic acid dehydratase activity was determined. There was no discernible inhibitory effect of tetraethyllead at any concentration, with or without pre-incubation. Pb(NO3)2 showed a distinct effect at an addition concentration of 1-mu-M, with a substantial inhibition only following pre-incubation. Triethyllead acetate showed no difference in effect with pre-incubation. In the second experiment, the activating effects of zinc chloride (60-mu-M) and dithiothreitol (20 mM) on delta-aminolevulinic acid dehydratase activity were examined on four human blood samples in the presence of varying concentrations of Pb(NO3)2 (0-50-mu-M) and triethyllead acetate (0-1000-mu-M). The addition of zinc chloride alone showed little effect on enzyme activity, while dithiothreitol alone caused a substantial activation of the enzyme at all lead concentrations. The addition of both zinc chloride and dithiothreitol caused an even greater activation of the enzyme. The data indicate that Pb(NO3)2 is a much more potent inhibitor of delta-aminolevulinic acid dehydratase activity than triethyllead acetate (Ki values of 0.77-mu-M versus 130.37-mu-M, respectively). The use of delta-aminolevulinic acid dehydratase activity as an indicator of exposure may be questionable in cases of alkyllead exposure. Possible causes for differences in the inhibition of delta-aminolevulinic acid dehydratase by these compounds is also discussed.