Journal of Bioenergetics and Biomembranes

, Volume 27, Issue 2, pp 151–159 | Cite as

5-Aminolevulinate synthase and the first step of heme biosynthesis

  • Gloria C. Ferreira
  • Jian Gong
Article

Abstract

5-Aminolevulinate synthase catalyzes the condensation of glycine and succinyl-CoA to yield 5-aminolevulinate. In animals, fungi, and some bacteria, 5-aminolevulinate synthase is the first enzyme of the heme biosynthetic pathway. Mutations on the human erythroid 5-aminolevulinate synthase, which is localized on the X-chromosome, have been associated with X-linked sideroblastic anemia. Recent biochemical and molecular biological developments provide important insights into the structure and function of this enzyme. In animals, two aminolevulinate synthase genes, one housekeeping and one erythroid-specific, have been identified. In addition, the isolation of 5-aminolevulinate synthase genomic and cDNA clones have permitted the development of expression systems, which have tremendously increased the yields of purified enzyme, facilitating structural and functional studies. A lysine residue has been identified as the residue involved in the Schiff base linkage of the pyridoxal 5′-phosphate cofactor, and the catalytic domain has been assigned to the C-terminus of the enzyme. A conserved glycine-rich motif, common to all aminolevulinate synthases, has been proposed to be at the pyridoxal 5′phosphate-binding site. A heme-regulatory motif, present in the presequences of 5-aminolevulinate synthase precursors, has been shown to mediate the inhibition of the mitochondrial import of the precursor proteins in the presence of heme. Finally, the regulatory mechanisms, exerted by an iron-responsive element binding protein, during the translation of erythroid 5-aminolevulinate synthase mRNA, are discussed in relation to heme biosynthesis.

Key words

Heme 5-aminolevulinate pyridoxal 5′-phosphate mitochondria heme metabolism 

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Gloria C. Ferreira
    • 1
    • 2
    • 3
  • Jian Gong
    • 1
    • 2
  1. 1.Department of Biochemistry and Molecular Biology, College of MedicineUniversity of South FloridaTampa
  2. 2.Institute for Biomolecular ScienceUniversity of South FloridaTampa
  3. 3.The H. Lee Moffitt Cancer Center and Research InstituteUniversity of South FloridaTampa

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