Heme Metabolites in Blood and Urine in Relation to Lead Toxicity and Their Determination

Abstract

Publisher Summary Lead causes partial inhibition at several enzymatic steps in the biosynthesis of heme, reduces the bioavailability of iron and, in erythroid cells, impairs globin synthesis. In humans, the combination is pathognomonic for lead: inhibition of δ-aminolevulinate dehydratase (ALAD) activity, as assayed in vitro in circulating erythrocytes; increased excretion of δ-aminolevulinic acid in urine (ALAU); increased excretion of Type III coproporphyrin in urine (CPU); and accumulation of zinc protoporphyrin (ZnP) in erythrocytes. In most methods of analysis of lead poisoning, ZnP is measured as “free” erythrocyte protoporphyrin (FEP). Recently developed microscale fluorometric methods permit quantitative determination of FEP in 20 μl of whole blood or less. Microtests for FEP and ZnP, referred to generically as erythrocyte protoporphyrin (EP) tests, are now in wide use in screening for prevention of pediatric plumbism. Microscale methods for measurement of in erythrocytes ALAD activity are also in wide use in epidemiological studies. Recent experimental data strongly suggest that the inhibitory effects of lead in the biosynthetic pathway for heme formation can be modified in animals by altering the concentrations of other essential and nonessential trace metals. Although intralaboratory precision is often satisfactory, interlaboratory comparisons reveal substantial differences between laboratories in the measurement of blood lead, δ-aminolevulinate dehydratase (ALAD), δ-aminolevulinic acid (ALAU), and free erythrocyte protoporphyrin (FEP).