Influence of the Common Human Delta-aminolevulinate Dehydratase Polymorphism on Lead Body Burden

Overview

Journal Environ Health Perspect

Date 1994 Sep 1

PMID 7843101

Citations 17

Authors

J G Wetmur

Affiliations

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Abstract

delta-Aminolevulinate dehydratase (ALAD) is the second enzyme in the heme biosynthesis pathway. ALAD is a zinc metalloenzyme, and its inhibition by lead substitution for zinc is one of the most sensitive indicators of blood-lead accumulation, a measure of recent lead exposure. Stoichiometry calculations indicate that a significant portion of blood lead is stored in ALAD. Human ALAD exhibits a charge polymorphism, with about 20% of Caucasians expressing the rarer ALAD2 allele. Human ALAD1 and ALAD2 cDNAs and the 16-kb ALAD gene have been cloned and sequenced. A simple polymerase chain reaction test has been established and validated for determining ALAD genotypes. Two population studies have indicated that lead-exposed individuals with the ALAD2 allele have blood-lead levels about 10 micrograms/dl greater than similarly exposed individuals carrying only the ALAD1 allele. Ongoing work is directed toward determining the biochemistry underlying the allele-specific accumulation of blood lead, and toward determining the contribution of human ALAD genotype to lead accumulation in other tissues in transgenic mouse models and to final lead deposition in bone in both mouse and man.

Citing Articles

Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

Huang C, Yang C, Liu T, Dai C, Wang C, Chuang H Int J Environ Res Public Health. 2020; 17(16).

PMID: 32784669 PMC: 7460038. DOI: 10.3390/ijerph17165712.

Genetic Risk Factors for Essential Tremor: A Review.

Siokas V, Aloizou A, Tsouris Z, Liampas I, Aslanidou P, Dastamani M Tremor Other Hyperkinet Mov (N Y). 2020; 10:4.

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Lead: Tiny but Mighty Poison.

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δ-Aminolevulinate Dehydratase Activity is Stimulated in a MPTP Mouse Model of Parkinson's Disease: Correlation with Myeloperoxidase Activity.

Sampaio T, Marcondes Sari M, Pesarico A, Nogueira C Cell Mol Neurobiol. 2016; 37(5):911-917.

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Ding N, Wang X, Weisskopf M, Sparrow D, Schwartz J, Hu H PLoS One. 2016; 11(9):e0161472.

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References

Muller W, Snyder S . delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Ann Neurol. 1977; 2(4):340-2. DOI: 10.1002/ana.410020415. View

Astrin K, Bishop D, Wetmur J, Kaul B, DAVIDOW B, Desnick R . delta-Aminolevulinic acid dehydratase isozymes and lead toxicity. Ann N Y Acad Sci. 1987; 514:23-9. DOI: 10.1111/j.1749-6632.1987.tb48757.x. View

Anderson P, Desnick R . Purification and properties of delta-aminolevulinate dehydrase from human erythrocytes. J Biol Chem. 1979; 254(15):6924-30. View

Brennan M, Cantrill R . Delta-aminolaevulinic acid is a potent agonist for GABA autoreceptors. Nature. 1979; 280(5722):514-5. DOI: 10.1038/280514a0. View

Doss M, von Tiepermann R, Schneider J, Schmid H . New type of hepatic porphyria with porphobilinogen synthase defect and intermittent acute clinical manifestation. Klin Wochenschr. 1979; 57(20):1123-7. DOI: 10.1007/BF01481493. View

Brennan M, Cantrill R . Delta-Aminolaevulinic acid and amino acid neurotransmitters. Mol Cell Biochem. 1981; 38 Spec No(Pt 1):49-58. DOI: 10.1007/BF00235687. View

Battistuzzi G, Petrucci R, Silvagni L, Urbani F, Caiola S . delta-Aminolevulinate dehydrase: a new genetic polymorphism in man. Ann Hum Genet. 1981; 45(3):223-9. DOI: 10.1111/j.1469-1809.1981.tb00333.x. View

Doss M, Muller W . Acute lead poisoning in inherited porphobilinogen synthase (delta-aminolevulinic acid dehydrase) deficiency. Blut. 1982; 45(2):131-9. DOI: 10.1007/BF00319941. View

Petrucci R, Leonardi A, Battistuzzi G . The genetic polymorphism of delta-aminolevulinate dehydrase in Italy. Hum Genet. 1982; 60(3):289-90. DOI: 10.1007/BF00303023. View

10.

Benkmann H, Bogdanski P, GOEDDE H . Polymorphism of delta-aminolevulinic acid dehydratase in various populations. Hum Hered. 1983; 33(1):62-4. DOI: 10.1159/000153351. View

11.

Winneke G, Kramer U, Brockhaus A, Ewers U, Kujanek G, Lechner H . Neuropsychological studies in children with elevated tooth-lead concentrations. II. Extended study. Int Arch Occup Environ Health. 1983; 51(3):231-52. DOI: 10.1007/BF00377755. View

12.

Giampietro P, Desnick R . Determination of delta-aminolevulinate dehydratase activity by a specific fluorometric coupled-enzyme assay. Anal Biochem. 1983; 131(1):83-92. DOI: 10.1016/0003-2697(83)90138-0. View

13.

Doss M, LAUBENTHAL F, Stoeppler M . Lead poisoning in inherited delta-aminolevulinic acid dehydratase deficiency. Int Arch Occup Environ Health. 1984; 54(1):55-63. DOI: 10.1007/BF00378728. View

14.

CHISOLM Jr J, Thomas D, Hamill T . Erythrocyte porphobilinogen synthase activity as an indicator of lead exposure in children. Clin Chem. 1985; 31(4):601-5. View

15.

Audesirk G . Effects of lead exposure on the physiology of neurons. Prog Neurobiol. 1985; 24(3):199-231. DOI: 10.1016/0301-0082(85)90006-1. View

16.

Cutler M, Mclaughlin M, McNeil E, Moore M . Effects of delta-aminolaevulinic acid on contractile activity in the isolated small intestine of the rabbit. Role of adrenergic receptors. Neuropharmacology. 1985; 24(10):1005-9. DOI: 10.1016/0028-3908(85)90129-7. View

17.

Rogan W, Reigart J, Gladen B . Association of amino levulinate dehydratase levels and ferrochelatase inhibition in childhood lead exposure. J Pediatr. 1986; 109(1):60-4. DOI: 10.1016/s0022-3476(86)80573-x. View

18.

Bishop T, Cohen P, Boyer S, Noyes A, Frelin L . Isolation of a rat liver delta-aminolevulinate dehydrase (ALAD) cDNA clone: evidence for unequal ALAD gene dosage among inbred mouse strains. Proc Natl Acad Sci U S A. 1986; 83(15):5568-72. PMC: 386329. DOI: 10.1073/pnas.83.15.5568. View

19.

Wetmur J, Bishop D, Cantelmo C, Desnick R . Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A. 1986; 83(20):7703-7. PMC: 386789. DOI: 10.1073/pnas.83.20.7703. View

20.

Ziemsen B, Angerer J, Lehnert G, Benkmann H, GOEDDE H . Polymorphism of delta-aminolevulinic acid dehydratase in lead-exposed workers. Int Arch Occup Environ Health. 1986; 58(3):245-7. DOI: 10.1007/BF00432107. View