Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
(1997) In Basic and Clinical Pharmacology and Toxicology 81(4). p.153-158- Abstract
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 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.... (More)
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 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 ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 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 ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
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- author
- Bergdahl, Ingvar A. LU ; Grubb, Anders LU ; Schütz, Andrejs LU ; Desnick, Robert J. ; Wetmur, James G. ; Sassa, Shigeru and Skerfving, Staffan LU
- organization
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Aged, Alleles, Chromatography, Liquid, Erythrocytes/drug effects, Gene Expression Regulation, Enzymologic/drug effects, Humans, Lead/blood, Male, Mass Spectrometry, Middle Aged, Molecular Weight, Occupational Exposure, Polymorphism, Genetic/drug effects, Porphobilinogen Synthase/blood, Protein Binding, Spectrophotometry, Atomic
- in
- Basic and Clinical Pharmacology and Toxicology
- volume
- 81
- issue
- 4
- pages
- 153 - 158
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:0030764036
- pmid:9353844
- ISSN
- 0901-9928
- DOI
- 10.1111/j.1600-0773.1997.tb02061.x
- language
- English
- LU publication?
- yes
- id
- 9d4b0ca1-c993-46a2-adea-7a7376dc4a0e
- date added to LUP
- 2021-10-29 09:54:47
- date last changed
- 2024-04-06 11:21:29
@article{9d4b0ca1-c993-46a2-adea-7a7376dc4a0e, abstract = {{<p>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 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 ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 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 ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.</p>}}, author = {{Bergdahl, Ingvar A. and Grubb, Anders and Schütz, Andrejs and Desnick, Robert J. and Wetmur, James G. and Sassa, Shigeru and Skerfving, Staffan}}, issn = {{0901-9928}}, keywords = {{Adult; Aged; Alleles; Chromatography, Liquid; Erythrocytes/drug effects; Gene Expression Regulation, Enzymologic/drug effects; Humans; Lead/blood; Male; Mass Spectrometry; Middle Aged; Molecular Weight; Occupational Exposure; Polymorphism, Genetic/drug effects; Porphobilinogen Synthase/blood; Protein Binding; Spectrophotometry, Atomic}}, language = {{eng}}, number = {{4}}, pages = {{153--158}}, publisher = {{Wiley-Blackwell}}, series = {{Basic and Clinical Pharmacology and Toxicology}}, title = {{Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes}}, url = {{http://dx.doi.org/10.1111/j.1600-0773.1997.tb02061.x}}, doi = {{10.1111/j.1600-0773.1997.tb02061.x}}, volume = {{81}}, year = {{1997}}, }