Immunochemical studies of the uroporphyrinogen decarboxylase defect caused by hexachlorobenzene

Immunoreactive and catalytic uroporphyrinogen decarboxylase has been measured in the livers of rodents made porphyric by hexachlorobenzene (HCB). Catalytic activity decreased progressively as porphyria developed but was not accompanied by a fall in the concentration of immunoreactive enzyme protein. These findings suggest that HCB specifically inactivates uroporphyrinogen decarboxylase without affecting those regions of the molecule that determine its antigenic activity and without increasing its rate of catabolism. In vitro, uroporphyrin-catalysed photoinactivation of uroporphyrinogen decarboxylase was similarly unaccompanied by loss of immunoreactivity, whereas reaction of sulfhydryl groups with N-ethylmaleimide led to loss of both catalytic activity and immunoreactivity. These results suggest that, if HCB causes chronic porphyria by modifying sulfhydryl groups in the enzyme, the effect is restricted to catalytic or substrate-binding sites.