Disease relevance of sialic acid

• Sialic acid storage diseases (SASD, MIM 269920) are autosomal recessive neurodegenerative disorders that may present as a severe infantile form (ISSD) or a slowly progressive adult form, which is prevalent in Finland (Salla disease) [1].
• BACKGROUND: The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases [2].
• Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid [3].
• Monoclonal antibody Mab D1.1 recognizes on human melanoma cells a ganglioside antigen characterized by an alkali-labile O-acetylated sialic acid residue [4].
• These findings suggest that sialic acid on the cell surface may play a role in tumor cell metastasis [5].

Psychiatry related information on sialic acid

• Salla disease is a lysosomal storage disorder characterized by mental retardation and disturbed sialic acid metabolism [6].
• In senile dementia, marked diminution of total ganglioside sialic acid per neuron and galactocerebroside per cell in the lower lamina far exceeded alterations associated with aging itself [7].
• Neuraminidase treatment of proteoglycan-deficient cells restores permissiveness to GDVII virus, indicating that sialic acid hinders direct access of virus to the protein entry receptor [8].
• The forms of transferrin deficient in sialic acid and/or carbohydrate, termed carbohydrate-deficient transferrin (CDT), have been of clinical interest for almost two decades as a result of the initial finding that elevated CDT concentrations are associated with chronic, excessive alcohol abuse [9].
• Carbohydrate-deficient transferrin (CDT) is the most specific marker for diagnosis of chronic excessive alcohol consumption and includes the serum transferrin (Tf) isoforms with two or less sialic acid residues (di-, mono-, and asialo-Tf) [10].

High impact information on sialic acid

• CD22 is a member of the Ig superfamily that serves as an adhesion receptor for sialic acid-bearing ligands expressed on erythrocytes and all leukocyte classes [11].
• ST3Gal-I induction and attendant core 1 sialic acid addition to CD8beta on mature thymocytes decreases CD8alphabeta-MHCI avidity by altering CD8alphabeta domain-domain association and/or orientation [12].
• Our observations suggest that mutations in SLC17A5 are the primary cause of lysosomal sialic acid storage diseases [1].
• Progressive cerebellar atrophy and dysmyelination have been documented by magnetic resonance imaging (ref. 4). Enlarged lysosomes are seen on electron microscopic studies and patients excrete large amounts of free sialic acid in urine [1].
• Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of terminal sialic acid residues of glyconjugates [13].

Chemical compound and disease context of sialic acid

• Fibroblast granular fractions of patients with Salla disease exhibited negligible egress of sialic acid, whether endogenous or derived from N-acetylmannosamine exposure [14].
• The polydiacetylene layer is functionalized with an analog of sialic acid, the receptor-specific ligand for the influenza virus hemagglutinin [15].
• Serum protein-bound carbohydrates, L-fucose, sialic acid, D-galactose, and D-mannose, were measured as potential biologic markers in patients with breast cancer with the use of high-resolution anion exchange separation in combination with a sensitive cerate oxidimetric fluorescence detector system [16].
• Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs [17].
• For 22 randomly selected patients with proved metastatic breast cancer, both L-fucose and sialic acid levels were above the normal range in 21 patients (95%) [16].

Biological context of sialic acid

• There is evidence that part of this recycling process involves the distal region of the Golgi complex, where terminal glycosylation occurs: when the plasma membrane transferrin receptor is desialylated by neuraminidase treatment, it acquires new sialic acid molecules after endocytosis and before cell-surface re-expression [18].
• Complement targeting of nonhuman sialic acid does not mediate cell death of human embryonic stem cells [19].
• Codons under positive selection were associated with antibody combining site A or B or the sialic acid receptor binding site [20].
• Modification of cell surface molecules with sialic acid is crucial for their function in many biological processes, including cell adhesion and signal transduction [21].
• Removal of sialic acid from a specific hepatic binding protein virtually abolishes its capacity to bind certain asialoglycoproteins [22].

Anatomical context of sialic acid

• A H+/anionic sugar symporter mechanism for sialic acid and glucuronic acid is impaired in lysosomal membranes from Salla and ISSD patients [1].
• A second type of receptor, largely masked by sialic acid, appears throughout the extracellular matrix [23].
• However, sialic acid-containing receptors have been implicated in the adherence of M. pneumoniae to erythrocytes and other cell types, and both I and the related antigen i occur on erythrocytes in sialylated form: i is the predominant antigen on fetal erythrocytes and I is predominant in adults [24].
• Sialic acid residues are important calcium-binding sites in the matrix and treatment with neuraminidase, an enzyme which cleaves sialic acid from oligosaccharide chains, has been reported to abolish spontaneous contraction in cultured heart cells, without causing general breakdown in the plasma membrane [25].
• MAdCAM-1 isolated from mesenteric lymph nodes, but not from cultured endothelioma cells, bears N-glycanase-resistant sialic acid-containing carbohydrate which supports adhesion of L-selectin-transfected lymphoid cells under shear [26].

Associations of sialic acid with other chemical compounds

• This region of the Golgi apparatus exhibited both TPPase and CMPase activity and was the intracellular site where sialic acid residues bound to glycoprotein were detected using the Limax flavus lectin [27].
• The 35S label was located in asparagine-linked carbohydrates on both glycopeptides (molecular weights, 170,000 and 140,000) but not in the sialic acid [28].
• Neuraminidase treatment of the gamma/delta T cells or addition of ethylenediaminetetraacetic acid (EDTA) to the assay abrogates binding, demonstrating the importance of sialic acid and divalent cations, which is consistent with other E-selectin-mediated adhesion events [29].
• Neither sialic acid, galactose, manose, nor N-acetyl-glucosamine alone inhibits rosette formation [30].
• The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion [31].

Gene context of sialic acid

• Because the asialoglycoprotein (ASGP) receptor is specifically expressed in the liver at high density, the ASGP receptor-binding domain was generated within an N-glycosylated human IFN-beta molecule by the removal of sialic acid to direct this cytokine to the liver [32].
• Similar to other sialoadhesin molecules, p75/AIRM1 appears to mediate sialic acid-dependent ligand recognition [33].
• Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140 [34].
• The neural cell adhesion molecule (N-CAM) has an unusually high amount of sialic acid (28-35 g/100 g of polypeptide) and shows microheterogeneity in electrophoretic gels in its embryonic or E form [35].
• Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12 [36].

Analytical, diagnostic and therapeutic context of sialic acid

• By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons [37].
• Sialic acid was demonstrated to be the fH target by flow cytometry that showed a fourfold increase in fH binding that was reversed by neuraminidase-mediated cleavage of sialic acid off gonococci [38].
• Sialic acid prevented both enhancement by vitamin D-binding protein of the chemotactic activity of native C5a des Arg and formation of C5a des Arg-vitamin D-binding protein complexes, detected by molecular sieve chromatography [39].
• These studies indicated that tissue sialic acid levels may provide a simple and reliable screening technique in the early diagnosis of premalignant change in all regions of the colon [40].
• We have identified a major membrane sialoprotein in human glomeruli that is similar to rat podocalyxin in its sialic acid-dependent binding of wheat germ agglutinin and in its localization on the surface of glomerular epithelial and endothelial cells, as shown by immunoelectron microscopy, using the monoclonal antibody PHM5 [41].

References