SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-06-1851. This Article Full Text (PDF) All Versions of this Article: 2002-06-1851v1 101/1/345    most recent Alert me when this article is cited Alert me if a correction is posted 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 van Wijk, R. Articles by van Solinge, W. W Search for Related Content PubMed PubMed Citation Articles by van Wijk, R. Articles by van Solinge, W. W Social Bookmarking                   What's this? Submitted June 24, 2002 Accepted July 29, 2002 HK Utrecht: missense mutation in the active site of human hexokinase associated with hexokinase deficiency and severe nonspherocytic hemolytic anemia Richard van Wijk, Gert Rijksen, Eric G Huizinga, Hendrik K Nieuwenhuis, and Wouter W van Solinge* Department of Clinical Chemistry, University Medical Center Utrecht, Utrecht, The Netherlands Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Crystal & Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands * Corresponding author; email: wsolinge{at}lab.azu.nl. Hexokinase deficiency is a rare autosomal recessive disease with a clinical phenotype of severe hemolysis. We report a novel homozygous missense mutation in exon 15 (c.2039C>G, HK Utrecht) of HK1, the gene that encodes red blood cell specific hexokinase-R, in a patient previously diagnosed with hexokinase deficiency. The T680S substitution predicted by this mutation affects a highly conserved residue in the enzyme's active site that interacts with phosphate moieties of ADP, ATP and inhibitor glucose-6-phosphate. We correlated the molecular data to the severe clinical phenotype of the patient by means of altered enzymatic properties of partially purified hexokinase from the patient, notably with respect to Mg2+-ATP binding. These kinetic properties contradict with those obtained from a recombinant mutant brain hexokinase-I with the same T680S substitution. It thereby stresses the valuable contribution of studying patients with hexokinase deficiency towards a better understanding of its key role in glycolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Bonnefond, M. Vaxillaire, Y. Labrune, C. Lecoeur, J.-C. Chevre, N. Bouatia-Naji, S. Cauchi, B. Balkau, M. Marre, J. Tichet, et al. Genetic Variant in HK1 Is Associated With a Proanemic State and A1C but Not Other Glycemic Control-Related Traits Diabetes, November 1, 2009; 58(11): 2687 - 2697. [Abstract] [Full Text] [PDF] K. M.K. de Vooght, W. W. van Solinge, A. C. van Wesel, S. Kersting, and R. van Wijk First mutation in the red blood cell-specific promoter of hexokinase combined with a novel missense mutation causes hexokinase deficiency and mild chronic hemolysis Haematologica, September 1, 2009; 94(9): 1203 - 1210. [Abstract] [Full Text] [PDF] R. van Wijk and W. W. van Solinge The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis Blood, December 15, 2005; 106(13): 4034 - 4042. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020