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Tetrapyrroles pp 116-127 | Cite as

Regulation of Mammalian Heme Biosynthesis

  • Amy E. Medlock
  • Harry A. Dailey
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

Regulation of the heme biosynthetic pathway in mammals occurs via two distinct mechanisms. These mechanisms reflect the fact that while most cells need to closely regulate relatively low levels of intracellular heme, differentiating erythroid cells must produce massive amounts of heme during a short period to satisfy the needs of hemoglobinization. In erythroid precursor cells all pathway enzymes are induced via erythroid-specific promoter elements and the first enzyme, erythroid-specific 5-aminolevulinate synthase (ALAS-2) encoded by a gene on the X chromosome, is also subject to translational regulation due to the presence of an iron-responsive element located in the 5′ end of the mRNA. In nonerythroid cells a house-keeping regulatory scheme exists where most regulation appears to be via transcriptional regulation of a housekeeping 5-aminolevulinate synthase (ALAS-1) that is encoded on human chromosome 3. While the proteins of the mature forms of ALAS-1 and ALAS-2 are highly similar, the regulatory elements that control their expression are distinctly different and only ALAS-2 mRNA possesses an iron-regulatory element. Additional regulatory features exist throughout the pathway, but the major regulation appears to occur at the level of ALAS.

Keywords

Erythroid Differentiation Heme Biosynthesis Iron Responsive Element Erythroid Precursor Cell Variegate Porphyria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Biomedical and Health Sciences Institute, Paul D. Coverdell CenterUniversity of GeorgiaAthensUSA

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