Document Detail

Gangliosides potentially inhibit extracellular nucleotide metabolism.
MedLine Citation:
PMID:  16918351     Owner:  NLM     Status:  MEDLINE    
Gangliosides are glycolipids that contain sialic acid and they are mainly located on the outer leaflet of the cellular plasma membrane of most vertebrate and some invertebrate cells. Because they have structurally diverse, bulky and negatively charged oligosaccharide moieties, gangliosides endow cell membranes with unique molecular characteristics. Although they are abundant in the central nervous system (CNS), the complete loss of gangliosides in mice does not result in gross morphological abnormalities of the CNS. However, mutant mice develop neurodegenerative diseases and die soon after birth, suggesting that gangliosides are required for the maintenance and development of a stable CNS and are crucial to sustain life. At the cellular level, gangliosides influence cell growth and death, probably because they are involved in the lipid-mediated assembly of signaling molecules such as growth factor receptors or integrins on the membranes. This article addresses the structural similarity between the tandem sialic acid residues of gangliosides and nicotinamide adenine dinucleotide (NAD(+)) determined from biochemical data showing that gangliosides inhibit NAD(+) glycohydrolase activity and theoretical considerations. An essential feature of the structural similarity resides in a negative charge cluster formed by the two carboxyl groups in the tandem sialic acid residues and the diphosphate moiety of NAD(+). The potential physiological role(s) of gangliosides on the regulation of extracellular nucleotide metabolism are discussed.
Miki Hara-Yokoyama
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current medicinal chemistry     Volume:  13     ISSN:  0929-8673     ISO Abbreviation:  Curr. Med. Chem.     Publication Date:  2006  
Date Detail:
Created Date:  2006-08-21     Completed Date:  2006-09-11     Revised Date:  2007-02-12    
Medline Journal Info:
Nlm Unique ID:  9440157     Medline TA:  Curr Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2233-9     Citation Subset:  IM    
Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
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MeSH Terms
Cell Death
Cell Division
Enzyme Inhibitors / pharmacology
Gangliosides / biosynthesis*,  deficiency,  pharmacology*
Mice, Knockout
NAD+ Nucleosidase / antagonists & inhibitors
Nucleotides / antagonists & inhibitors*,  metabolism*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Gangliosides; 0/Nucleotides; EC Nucleosidase

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