Regulation and gene expression of heme synthesis under heavy metal exposure--review

J Environ Pathol Toxicol Oncol. 2010;29(2):137-58. doi: 10.1615/jenvironpatholtoxicoloncol.v29.i2.70.


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 dependent 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.

Publication types

  • Review

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics
  • Animals
  • Cadmium / toxicity
  • Copper / toxicity
  • Ferrochelatase / genetics
  • Gene Expression Regulation / drug effects*
  • Heme / biosynthesis*
  • Heme Oxygenase (Decyclizing) / genetics
  • Homeostasis
  • Humans
  • Hydroxymethylbilane Synthase / genetics
  • Iron / metabolism
  • Lead Poisoning / metabolism
  • Metals, Heavy / toxicity*
  • Photochemotherapy
  • Porphobilinogen Synthase / genetics


  • Metals, Heavy
  • Cadmium
  • Heme
  • Copper
  • Iron
  • Heme Oxygenase (Decyclizing)
  • 5-Aminolevulinate Synthetase
  • Hydroxymethylbilane Synthase
  • Porphobilinogen Synthase
  • Ferrochelatase