LEAD BINDING TO DELTA-AMINOLEVULINIC-ACID DEHYDRATASE (ALAD) IN HUMANERYTHROCYTES

Over 99% of the lead present in blood is usually found in erythrocytes . To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythr ocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-bindi ng protein had a mass of approximately 240 kDa, and adsorption to spec ific antibodies showed that the protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocyte s was bound primarily to haemoglobin has to be revised. Furthermore, i n lead-exposed workers, the percentage of lead bound to ALAD was influ enced by a common polymorphism in the ALAD gene. Specifically, in seve n carriers of the ALAD(2) allele, 84% of the protein-bound lead recove red was bound to ALAD compared to 81% in seven homozygotes for the ALA D(1) allele whose erythrocytes were matched for blood-lead concentrati on. The small difference was statistically significant in Wilcoxon mat ched-pairs signed-rank test (P=0.03). No ALAD allele-specific differen ce in ALAD-bound lead was found among 20 unexposed controls. Perhaps t he difference in ALAD-bound lead can provide an explanation for the pr eviously reported finding of higher blood-lead levels among carriers o f the ALAD(2) allele than among ALAD(1) homozygotes in lead-exposed po pulations.