METABOLIC EFFECTS OF LEAD POISONING IN CHILDHOOD

  • Piomelli, Sergio S. (PI)

Project: Research project

Project Details

Description

These studies will investigate the biochemical effects of childhood lead poisoning and their metabolic and clinical significance. The focus will be on the elevation of erythrocyte protoporphyrin (EP) induced by Pb toxicity, since this indicates inhibition of an essential mitochondrial step: the insertion of iron into protoporphyrin to form heme. This project will evaluate the threshold of the effect of Pb on EP elevation in children and adults exposed to the "normal" level of environmental pollution and the significance of Fe deficiency. This project will evaluate the clinical significance of EP elevation and other metabolic indicators of Pb toxicity, by correlating biochemical findings with clincal symptomatology and with neuro-behavioral distrubances. This project will evaluate the biochemical mechanism of interference by Pb with the ferrochelatase step, which results in accumulation of protoporphyrin. It will investigate the hypothesis that Pb competes with iron, that Pb interferes with mitochondrial transport of iron, that mitochondrial Pb concentration is greater than blood Pb concentration, that Pb inhibits ferrochelatase synthesis. In addition, this project will investigate the species and tissue specificity of the Pb effect on ferrochelatase. Previous work on this project has demonstrated: EP elevation is the best indicator of Pb toxicity; the low threshold for an EP effects; the extremely low Pb level in remote unexposed populations; the clinical relevance of EP elevation and the competitive inhibition of Pb for ferrochelatase function. This project will further define the epidemiological, clincial and biochemical relevance of Pb effect on the last step of heme biosynthesis mediated by ferrochelatase, an enzyme located in the inner cristae of the mitochondria.
StatusFinished
Effective start/end date7/1/8511/30/87

Funding

  • National Institute of Environmental Health Sciences

ASJC Scopus Subject Areas

  • Biochemistry

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