Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase

Trace metals which produce experimental uroporphyrinuria in animals during prolonged exposure inhibit uroporphyrinogen (uro) decarboxylase in rat liver extracts $\text{in}\text{,}\text{vitro}$. Inhibitory effects are prevented by sulfhydryl reagents, suggesting metal binding to sulfhydryl groups of the enzyme as the likely mode of action. Mercury, the most potent of the metals tested with respect to sulfur binding kinetics, produces the greatest inhibition of enzyme activity. In contrast, iron, which is considered to play a role in the etiology of porphyria cutanea tarda (PCT) via inhibition of uro decarboxylase, did not inhibit the enzyme in the present test system, suggesting an indirect mode of action $\text{in}\text{,}\text{vivo}$. These results suggest that direct inhibition of uro decarboxylase underlies uroporphyrinuria produced by prolonged trace metal exposure. Experimental inhibition of uro decarboxylase by trace metals may serve as a model for studying metal-induced uroporphyrinuria and PCT in humans.