Erythrocyte protoporphyrin levels study

Several other classes of proteins have also been implicated as possible targets for lead, including other proteins in the heme biosynthetic pathway, leadbinding proteins in the kidney and brain, and heat shock proteins (342, 500-502). Lead is known to affect several steps in the heme biosynthetic pathway other than that catalyzed by ALAD Other profound effects include stimulation of 5-aminolevulinic acid synthase (ALAS) and decreased levels of iron incorporation into protoporphyrin by ferrochelatase (see Section VI.E.2 and Fig. 34) (10, 503-505). However, not all of these effects are due to direct interactions between lead and enzymes in the heme biosynthetic pathway. For instance, the widespread assertion that lead inhibits ferrochelatase is not supported by studies on the isolated enzyme (506, 507). Furthermore, increased levels of both erythrocyte protoporphyrin IX (EP) and zinc protoporphyrin (ZPP) are observed at high BLLs, suggesting that ferrochelatase is stiU competent to insert zinc into EP and that the increased levels of EP and ZPP associated with lead poisoning are most likely caused by lead interfering with iron uptake or transport (see Sections VI.C.4 and VI.E) (10, 506, 507). 

Lead also has a toxic effect on the last step in the haem synthesis pathway, which is the insertion of iron into protoporphyrin to create haem. If the enzyme ferrochelatase, responsible for this change, is inhibited by lead, this fails to take place. The amount of protoporphyrin in the erythrocytes, called zinc-protoporphyrin or erythrocyte protoporphyrin (ZZP or EPP), can be used as a measure of this effect. However, it is a less useful measure in studies of the effects of low levels of lead exposure, as an increase in EPP may not be detected at blood levels below about 20jUg/dl (Piomelli et al, 1982), although this threshold for the effect may vary with age (Succop et al,this volume). Other factors, such as iron deficiency, can also cause an increase in EPP levels in the blood... 

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