The increased amount of lead bound to the ALAD 2 isozyme should result in decreased lead available to inhibit ferrochelatase
, which would thus be available to catalyze the formation of heme with subsequent formation of hemoglobin in the presence of [Fe.sup.2+].
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).
at the millennium: structures, mechanisms and [2Fe-S] clusters.
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.
First, there was no association of expression profile of these genes with pathologic change, and second, by comparison with the gene expression profile of a mutant mouse model of ferrochelatase insufficiency (Tutois et al.
Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.
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).
Coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase activities were assayed using lymphocytes, according to the methods reported previously (13-15).
In patient B, erythrocyte PBGD, uroporphyrinogen-III synthase, and uroporphyrinogen decarboxylase as well as lymphocyte coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase activities were additionally examined; all were within reference values.
Modulation of the phenotype in dominant erythropoietic protoporphyria by a low expression of the normal ferrochelatase