In contrast, the weaker binding of lead to ALAD1 results in more bioavailable lead that can inhibit ferrochelatase
As mentioned above, the two target sites in the biosynthetic pathway of heine by PbB are the sites of activity of ALAD and ferrochelatase
(Moore and Goldberg 1985).
Ferrochelatase activity in the proband was reduced to 25% of the mean value, as is typical for EPP patients (5).
Direct sequencing of the PCR-amplified fragment containing exon 5 revealed a missense mutation, T545G, which led to the conversion of Leu-182 to Arg in ferrochelatase.
However, subsequent research on ferrochelatase revealed that this enzyme catalyzes zinc as well as iron chelation by protoporphyrin (12,13).
An important exception to these ratios occurs with protoporphyria, in which an inherited ferrochelatase deficiency leads to a massive overproduction and accumulation of EP (11).
at the millennium: structures, mechanisms and [2Fe-S] clusters.
This porphyria is induced by the inhibition of ferrochelatase
probably caused by a griseofulvin adduct of protoporphyrin IX produced in a cytochrome P450 (Cyp)-mediated suicide reaction (Bellingham et al.
Coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase
activities were assayed using lymphocytes, according to the methods reported previously (13-15).
Modulation of the phenotype in dominant erythropoietic protoporphyria by a low expression of the normal ferrochelatase