The in vitro effects of zinc and manganese on delta-aminolevulinic acid dehydratase activity inhibited by lead or tin.

The effects of the administration of lead and tin on delta-aminolevulinic acid dehydratase (5-aminolevulinate hydro-lyase, ALAD, EC 4.2.1.24) activity in human, rabbit, and mouse blood were studied in vivo. In addition the ability of zinc, manganese, and dithiothreitol (DTT) to restore ALAD activity in the blood of lead- or tin-treated subjects was examined in vitro. Manganese, zinc, and DTT restored ALAD activity in vitro. The optimal concentration of zinc required in vitro was 10(-4) M in blood of lead-exposed humans and lead- or tin-administered mice, and 10(-3) M in blood of rabbits treated with either lead or tin. Even at the optimal concentration of zinc, the reactivating effect was incomplete, the highest recovery being about one-third of the control activity. However, the simultaneous addition of zinc and DTT increased ALAD activity to levels comparable with those of controls. Manganese was less effective than zinc in restoring ALAD activity in vitro; the effective dose was 10(-2) M in the blood of lead-exposed subjects, while little effect was noted in tin-treated subjects. Manganese was as effective as DTT in protecting against the inhibition of ALAD activity in vitro by excessive zinc. In contrast, DTT restored ALAD activity completely in the blood of tin-treated rabbits and produced about an 80% recovery of enzyme activity in the blood of tin-treated mice, but only a 35% recovery in the blood of lead-treated rabbits. These results suggest that the mechanisms by which lead and tin inhibit ALAD activity are different.