Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes

被引:131
作者
Bergdahl, IA
Grubb, A
Schutz, A
Desnick, RJ
Wetmur, JG
Sassa, S
Skerfving, S
机构
[1] LUND UNIV, DEPT CLIN CHEM, S-22185 LUND, SWEDEN
[2] MT SINAI SCH MED, DEPT HUMAN GENET, NEW YORK, NY USA
[3] MT SINAI SCH MED, DEPT MICROBIOL, NEW YORK, NY USA
[4] ROCKEFELLER UNIV, LAB BIOCHEM HEMATOL, NEW YORK, NY 10021 USA
来源
PHARMACOLOGY & TOXICOLOGY | 1997年 / 81卷 / 04期
关键词
D O I
10.1111/j.1600-0773.1997.tb02061.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that the protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD(2) allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD(1) allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P=0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD(2) allele than among ALAD(1) homozygotes in lead-exposed populations.
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页码:153 / 158
页数:6
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