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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3340-3345. Prepublished online as a Blood First Edition Paper on December 16, 2004; DOI 10.1182/blood-2004-10-3895. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3895v1 105/8/3340    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chiarelli, L. R. Articles by Valentini, G. Search for Related Content PubMed PubMed Citation Articles by Chiarelli, L. R. Articles by Valentini, G. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Functional analysis of pyrimidine 5'-nucleotidase mutants causing nonspherocytic hemolytic anemia Laurent R. Chiarelli, Paola Bianchi, Elisa Fermo, Alessandro Galizzi, Paolo Iadarola, Andrea Mattevi, Alberto Zanella, and Giovanna Valentini From the Department of Biochemistry "A. Castellani," University of Pavia, Italy; Department of Genetics and Microbiology "A. Buzzati-Traverso," University of Pavia, Italy; and Hematology Division, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Maggiore, Milano, Italy. Inherited pyrimidine 5'-nucleotidase type I (P5'N-1) deficiency is the third most common erythrocyte enzymopathy that causes hemolysis. Fourteen different mutations have been identified to date. We have investigated the molecular bases of the disease by studying the biochemical properties of the recombinant wild-type human enzyme and 4 variant proteins (D87V, L131P, N179S, and G230R) bearing missense mutations found in patients affected by nonspherocytic hemolytic anemia. P5'N-1 is a relatively stable protein and has essentially identical catalytic efficiency toward cytidine monophosphate (CMP) and uridine monophosphate (UMP). All investigated mutant proteins display impaired catalytic properties and/or reduced thermostability, providing a rationale for the pathological effects of the mutations. Despite the substantial changes in the kinetic and thermostability parameters, the enzyme activity detected in the red blood cells of patients homozygous for mutations L131P and G230R exhibits moderate alterations. This suggests that P5'N-1 deficiency is compensated, possibly by other nucleotidases or alternative pathways in nucleotide metabolism. Therefore, nucleotidase activity may not be considered a prognostic indicator in patients affected by the enzymopathy. (Blood. 2005;105:3340-3345) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Bitto, C. A. Bingman, G. E. Wesenberg, J. G. McCoy, and G. N. Phillips Jr Structure of Pyrimidine 5'-Nucleotidase Type 1: INSIGHT INTO MECHANISM OF ACTION AND INHIBITION DURING LEAD POISONING J. Biol. Chem., July 21, 2006; 281(29): 20521 - 20529. [Abstract] [Full Text] [PDF] J. T. Prchal and X. T. Gregg Red Cell Enzymes Hematology, January 1, 2005; 2005(1): 19 - 23. [Abstract] [Full Text] [PDF]

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