The insertion of ferrous iron ([Fe.sup.2+]) into the porphyrin ring to form heme is catalyzed by the mitochondrial enzyme ferrochelatase
, which shows reduced activity in the presence of lead (Ponka 1997).
Structure and function of ferrochelatase
. J Bioenerg Biomembr 1995; 27:221-9.
Nonaka, "Alteration of mRNA levels of S-aminolevulinic acid synthase, ferrochelatase
and heme oxygenase-1 in griseofulvin induced protoporphyria mice," Journal of Dermatological Science, vol.
Inhibition of ferrochelatase
to incorporate iron into protoporphyrin ring, leads to binding of zinc to protoporphyrin and form zinc protoporphyrin (30) (ZPP).
ZPP levels, derived from the substrate (protoporphyrin IX) of the last enzyme in the heme-synthesis system (ferrochelatase
), should only be increased by the presence of bioavailable lead; PbB that is strongly bound by an ALAD isozyme, for example, should not inhibit ferrochelatase
(d) A and E, PBGD; B, ferrochelatase
; C, UROD; D, PBGD/UROD/ coproporphyrinogen oxidase/protoporphyrinogen oxidase.
1976) Pb Inhibition of ferrochelatase
NOAEL: 25 [micro]g/dL resulting in accumulation of eryhrocyte protoporphyrin (Mushak et al.
The last enzyme in the porphyrin biosynthetic pathway is ferrochelatase
, an iron-sulfur protein (Dailey et al.
Erythropoietic protoporphyria (EPP) is an inherited disorder caused by a partial deficiency of the enzyme ferrochelatase
catalyzes the insertion of ferrous ions into protoporphyrin IX, the last step in heme biosynthesis.
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.
then catalyzes the chelation of a ferrous ion by protoporphyrin as the terminal reaction in heme formation (Fig.
This ZPP response occurs because iron and zinc interact as ferrochelatase
substrates, with zinc utilization increasing when the iron supply is diminished (1).