Pb inhibits the three enzymes responsible for heme synthesis; the heme: D-aminolevulinic acid dehydratase (ALAD), the coproporphyrinogen
decarboxylase and the ferrochelatase .
We showed that this probably results from the competitive inhibition of hydroxymethylbilane synthase by coproporphyrinogen
and protoporphyrinogen, substrates which accumulate in VP and HCP.
The association between a genetic polymorphism of coproporphyrinogen
oxidase, dental mercury exposure and neurobehavioral response in humans.
The steps in the heme synthesis pathway that are most vulnerable to heavy metal inhibition are those that involve the enzymes uroporphyrin decarboxylase (UROD) and coproporphyrinogen
d) A and E, PBGD; B, ferrochelatase; C, UROD; D, PBGD/UROD/ coproporphyrinogen
1991) showing that precoproporphyrin is formed as a consequence of Hg inhibition of uroporphyrinogen decarboxylase in the kidney during prolonged exposure, producing excess pentacarboxylporphyrinogen, which then competes with coproporphyrinogen
as a substrate for coproporphyrinogen
oxidase as the basis of precoproporphyrin formation (Woods et al.
2004) and the coproporphyrinogen
oxidase gene (Echeverria et al.
Important biochemical features of VP include the increased biliary excretion of coproporphyrinogen
and protoporphyrinogen and their corresponding porphyrins (4), which are commonly measured by fecal porphyrin analysis.
Lead is a potent inhibitor of [delta]-aminolevulinic acid dehydratase (ALAD), coproporphyrinogen
oxidase, and ferrochelatase, enzymes that catalyze the second, sixth, and final steps, respectively, in the biosynthesis of heme (Onalaja and Claudio 2000; Warren et al.
Her uroporphyrinogen III synthase activity was not measured, and the coproporphyrinogen
oxidase activity was increased threefold during a psychotic period, suggesting secondary porphyrinuria.
Pb depresses coproporphyrinogen
oxidase, resulting in increased coproporphyrin activity.
oxidase, protoporphyrinogen oxidase, and ferrochelatase activities were assayed using lymphocytes, according to the methods reported previously (13-15).