Biosynthesis of heme in mammals

Most iron in mammalian systems is routed to mitochondria to serve as a substrate for ferrochelatase. Ferrochelatase inserts iron into protoporphyrin IX to form heme which is incorporated into hemoglobin and cytochromes, the dominant hemoproteins in mammals. Tissue-specific regulatory features charac...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2006-07, Vol.1763 (7), p.723-736
Main Authors: Ajioka, Richard S., Phillips, John D., Kushner, James P.
Format: Article
Language:English
Subjects:
Animals
Crystallography, X-Ray
Ferrochelatase - chemistry
Ferrochelatase - metabolism
Heme
Heme - biosynthesis
Iron
Mammals - metabolism
Models, Molecular
Porphyrias
Porphyrin
Protein Conformation
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Summary:Most iron in mammalian systems is routed to mitochondria to serve as a substrate for ferrochelatase. Ferrochelatase inserts iron into protoporphyrin IX to form heme which is incorporated into hemoglobin and cytochromes, the dominant hemoproteins in mammals. Tissue-specific regulatory features characterize the heme biosynthetic pathway. In erythroid cells, regulation is mediated by erythroid-specific transcription factors and the availability of iron as Fe/S clusters. In non-erythroid cells the pathway is regulated by heme-mediated feedback inhibition. All of the enzymes in the heme biosynthetic pathway have been crystallized and the crystal structures have permitted detailed analyses of enzyme mechanisms. All of the genes encoding the heme biosynthetic enzymes have been cloned and mutations of these genes are responsible for a group of human disorders designated the porphyrias and for X-linked sideroblastic anemia. The biochemistry, structural biology and the mechanisms of tissue-specific regulation are presented in this review along with the key features of the porphyric disorders.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2006.05.005