Activation of uroporphyrinogen decarboxylase by ferrous iron in porphyria cutanea tarda

Abstract

Uroporphyrinogen decarboxylase was measured in the presence of ferrous iron, using mitochondria-free rat liver extracts as enzyme source. The activity of the enzyme was found to be increased at concentrations of ferrous iron from 0,01 mM, with maximal activity exhibited from 0,1 mM. Enzyme kinetics indicate that uroporphyrinogen decarboxylase reversibly binds ferrous iron, with a binding constant of approximately 5 x 10(4) mol-1. It is proposed that the effect of phlebotomy on patients with porphyria cutanea tarda is to mobilze storage iron in the liver to the active ferrous form, which activates hepatic uroporphyrinogen decarboxylase, the enzyme which is defective in this syndrome, with resultant clinical and biochemical remission.