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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

Online
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1437-4315
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Volume 390, Issue 7

Issues

Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis

Stefan O. Reinke
  • Beuth Hochschule für Technik Berlin, Fachbereich Life Sciences and Technology, Labor für Biochemie, Seestrasse 64, D-13347 Berlin, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gerhard Lehmer
  • Institut für Biochemie und Molekularbiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stephan Hinderlich
  • Beuth Hochschule für Technik Berlin, Fachbereich Life Sciences and Technology, Labor für Biochemie, Seestrasse 64, D-13347 Berlin, Germany
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  • De Gruyter OnlineGoogle Scholar
/ Werner Reutter
  • Institut für Biochemie und Molekularbiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-05-09 | DOI: https://doi.org/10.1515/BC.2009.073

Abstract

The key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed, is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). GNE is a highly conserved protein found throughout the animal kingdom. Its highest expression is seen in the liver and placenta. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. GNE knock-out in mice leads to embryonic lethality, emphasizing the crucial role of this key enzyme for sialic acid biosynthesis. The metabolic capacity to synthesize sialic acid and CMP-sialic acid upon ManNAc loads is amazingly high. An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. Due to the importance of increased concentrations of tumor-surface sialic acid, first attempts to find inhibitors of GNE have been successful.

Keywords: CMP-Neu5Ac; GlcNProp; h-IBM; ManNAc; sialic acid/Neu5Ac; UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE)

About the article

Corresponding author


Received: 2009-02-23

Accepted: 2009-04-03

Published Online: 2009-05-09

Published in Print: 2009-07-01


Citation Information: Biological Chemistry, Volume 390, Issue 7, Pages 591–599, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2009.073.

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