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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.15 5-Year IF: 1.4 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v29.i2.70
pages 137-158

Regulation and Gene Expression of Heme Synthesis Under Heavy Metal Exposure- Review

Avital Schauder
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
Almog Avital
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
Zvi Malik
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel


Environmental pollution of heavy metals is very abundant nowadays from industry, chemicals, old paints, and pipes or resulting from previous contaminants accumulating in the food chain. Most of the iron demands of the body are needed for heme synthesis and assembly, but iron is also required for Fe-S cluster proteins and other redox enzymes. Heme is an essential, iron-binding molecule used as a prosthetic group of hemoproteins or as a regulator in multiple cellular pathways. In this review, we focused on the effect of exposure to heavy metals, such as Pb, Ga, Cu, Kd, Hg and Al, on heme synthesis as the main iron-sequestering process of the human body. These metals compete with iron on transporters, reduce the cellular iron pool and moreover, bind to proteins, and cause physical and mental disturbances. Heavy metals mainly impair various aspects of the heme synthesis pathway: gene expression, enzyme activity, and iron integration into protoporphyrin IX. Main risk factors are described as well as effects on iron dependant processes in order to increase public awareness to the distribution of heavy metals in our close environment and the harsh consequences of exposure, even in low doses.

KEY WORDS: heme, heavy metals, iron, Pb, Ga, ALAD, PBGD

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