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Gangliosides Potentially Inhibit Extracellular Nucleotide Metabolism

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Abstract:

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.

Keywords: CD38; Gangliosides; NAD+; extracellular nucleotide metabolism; glycolipids; sialic acid

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986706777935177

Affiliations: Department of Hard Tissue Engineering, Biochemistry, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.

Publication date: August 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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