The interaction of lead exposure and arylsulfatase A genotype affects sulfatide catabolism in human fibroblasts

R. D. Poretz, A. Yang, Wenbin Deng, P. Manowitz

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Lead exposure causes cognitive and behavioral deficits in some affected children. We propose that a contributing mechanism for the neurological damage is that lead induces critically low levels of arylsulfatase A (ASA) at sensitive stages of nervous system development. It is hypothesized that the combined effects of a single nucleotide polymorphism (SNP) in human ASA which results in reduced levels of the enzyme, and lead concentrations which decrease ASA activity culminate in cellular enzymic activity that is below a critical threshold required for the maintenance of normal nervous system function. Human fibroblasts grown in the presence of 20 μM lead acetate exhibit a more than 60% decrease of cellular ASA enzyme protein. Lead treatment of cells from individuals with the SNP(s) of pseudodeficient ASA, but not those from subjects with the normal gene, results in a significant decrease in ability of the cells to desulfate sulfatide, the substrate of ASA. The decrease in the degree of sulfatide catabolism is consistent with possible enhanced lead-induced neurobehavioral effects in individuals homozygous for the pseudodeficiency polymorphism(s) of ASA. (C) 2000 Intox Press, Inc.

Original languageEnglish (US)
Pages (from-to)379-388
Number of pages10
Issue number3
StatePublished - 2000
Externally publishedYes


  • Arylsulfatase A
  • Lead
  • Metachromatic Leukodystrophy
  • Sulfatide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology


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