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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1098-1104. Prepublished online as a Blood First Edition Paper on April 14, 2005; DOI 10.1182/blood-2004-12-4661. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4661v1 106/3/1098    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Najahi-Missaoui, W. Articles by Dailey, H. A. Search for Related Content PubMed PubMed Citation Articles by Najahi-Missaoui, W. Articles by Dailey, H. A. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Production and characterization of erythropoietic protoporphyric heterodimeric ferrochelatases Wided Najahi-Missaoui, and Harry A. Dailey From the Biomedical and Health Sciences Institute and the Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA. Mutations resulting in diminished activity of the dimeric enzyme ferrochelatase are a prerequisite for the inherited disorder erythropoietic protoporphyria (EPP). Patients with clinical EPP have only 10% to 30% of normal levels of ferrochelatase activity, and although many patients with EPP have one mutant allele and one "low-expression" normal allele, the possibility remains that, for some, low ferrochelatase activity may result from an EPP mutation that has an impact on both subunits of the wild-type/mutant heterodimer. Here we present data for 12 ferrochelatase wild-type/EPP mutant heterodimers showing that some mutations result in heterodimers with the residual activity anticipated from individual constituents, whereas others result in heterodimers with significantly lower activity than would be predicted. Although the data do not allow an a priori prediction of heterodimeric residual activity based solely on the in vitro activity of EPP homodimers or the position of the mutated residue within ferrochelatase, mutations that affect the dimer interface or [2Fe-2S] cluster have a significantly greater impact on residual activity than would be predicted. These data suggest that some EPP mutations may result in clinically overt EPP in the absence of a low-expression, wild-type allele; this is of potential significance for genetic counseling of patients with EPP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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