| Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis. | |
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MedLine Citation:
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PMID: 19426133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Stefan O Reinke; Gerhard Lehmer; Stephan Hinderlich; Werner Reutter |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Biological chemistry Volume: 390 ISSN: 1431-6730 ISO Abbreviation: Biol. Chem. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-30 Completed Date: 2009-08-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9700112 Medline TA: Biol Chem Country: Germany |
Other Details:
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Languages: eng Pagination: 591-9 Citation Subset: IM |
Affiliation:
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Beuth Hochschule für Technik Berlin, Fachbereich Life Sciences and Technology, Labor für Biochemie, D-13347 Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbohydrate Epimerases / antagonists & inhibitors, genetics, metabolism Disease* Enzyme Inhibitors / pharmacology Humans N-Acetylneuraminic Acid / biosynthesis* Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 131-48-6/N-Acetylneuraminic Acid; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.60/N-acylmannosamine kinase; EC 5.1.3.-/Carbohydrate Epimerases; EC 5.1.3.14/UDP acetylglucosamine-2-epimerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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