Porphyrinogenic effect of hexachlorobenzene and 2,3,7,8-tetrachlorodibenzo-para-dioxin: is an inhibitor involved in uroporphyrinogen decarboxylase inactivation?

Uroporphyrinogen decarboxylase from control mouse liver was markedly inhibited in vitro by addition to the incubation mixture of cytosol fractions from livers of porphyric mice. The animals had been subjected to chronic treatment with 2,3,7,8-tetrachlorodibenzo-para-dioxin (25 micrograms/kg per week, intraperitoneally). The cytosol fractions were deproteinized by heating at 100 degrees C for 5 min and freed of porphyrins by treating the supernatants with Zerolit FF (i.p.) resin. Inhibition was proportional to the amount of fraction added and was not observed if the inhibitor fraction was dialysed before incubation. Increasing the substrate concentration did not reverse enzyme inhibition; the Vmax value calculated for the control enzyme in the presence of the inhibitor fraction was decreased, but Km did not vary. Two alternative hypotheses on the nature of the inhibitor compound(s) in the inhibitor fraction are discussed with relation to hexachlorobenzene (HCB) and 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) porphyria.