Disease relevance of N-acetylneuraminic acid

• Immunostaining for the lectin maackia amurensis agglutinin, which recognizes the Neu5Ac alpha 2,3 Gal sequence, which serves as a binding site for influenza A virus on target cell membranes, showed that positive staining was localized in the ventral substantia nigra and hippocampus [1].
• Neuraminidase (Vibrio cholerae) treatment of human metastatic mammary carcinoma MDA-MB-231 cells grown in culture released 0.60-0.63 mg of N-acetylneuraminic acid from 10(9) cells [2].
• To test this hypothesis, salivary secretion of volume, bicarbonate, and N-acetylneuraminic acid was measured in patients with reflux esophagitis, in age- and sex-matched controls, and in healthy young volunteers [3].
• H.p.l.c. analysis revealed that purified Neu5,9Ac2 is converted to Neu5Ac by incubation with influenza C virus [4].
• An efficient L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase was created by directed evolution from the Escherichia coli D-Neu5Ac (N-acetylneuraminic acid, D-sialic acid) aldolase [5].

Psychiatry related information on N-acetylneuraminic acid

• Glycosidation of N-acetylneuraminic acid by phase-transfer catalysis in chloroform-aqueous alkali gave several known and some new aryl alpha-ketosides in a short reaction time and in good yields [6].

High impact information on N-acetylneuraminic acid

• The specificity of the cross-reactivities was confirmed by testing the binding of the reactive anti-TEPC-15 MAb to both CRP and limulin in the presence of p-nitrophenylphosphorylcholine (pNPPC), N-acetylneuraminic acid, and bovine submaxillary mucin [7].
• The binding of the MAb to both CRP and limulin was strongly decreased by pNPPC, partially decreased by free PC, and not affected by N-acetylneuraminic acid or bovine submaxillary mucin [7].
• Two acceptors were prepared from fetuin for the assay, one by acid hydrolysis of N-acetylneuraminic acid and the other by the stepwise removal of N-acetylneuraminic acid and penultimate galactose by Smith degradation [8].
• Similar to invasion efficiency, binding requires N-acetylneuraminic acid (Neu5Ac) on human erythrocytes, specifically the glycophorins [9].
• Soluble Neu5Ac by itself in solution did not competitively inhibit the binding of EBA-175 to erythrocytes, suggesting that linkage to an underlying sugar is required for binding in contrast to charge alone [9].

Chemical compound and disease context of N-acetylneuraminic acid

• Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free N-acetylneuraminic acid (NeuAc, sialic acid) [10].
• Ganglioside GD1b is the target antigen for a biclonal IgM in a case of sensory-motor axonal polyneuropathy: involvement of N-acetylneuraminic acid in the epitope [11].
• Membrane-associated sialytransferase complexes from Escherichia coli K-235 catalyze the incorporation of N-acetylneuraminic acid (NeuNAc) from cytidine 5-monophospho-N-acetylneuraminic acid (CMP-NeuNAc) into polymeric products and a lipid fraction [12].
• The lipopolysaccharide (LPS) of non-typeable Haemophilus influenzae (NTHi) can be substituted at various positions by N-acetylneuraminic acid (Neu5Ac) [13].
• CHO clones containing integrated proviruses were selected with hygromycin or G418, and the subset of these with reduced cell surface Neu5Ac were then selected with wheat germ agglutinin (WGA) [14].

Biological context of N-acetylneuraminic acid

• Binding also occurred to the GD1a and GT1b gangliosides, which have the same end carbohydrate sequence except for the terminal N-acetylneuraminic acid, but the affinity was only 1-9% of that of the gangliosides with a terminal disialosyl linkage [15].
• In tissues of higher organisms homopolymers of alpha2,8-linked N-acetylneuraminic acid can be found as a posttranslational modification on selected proteins [16].
• These carbohydrate chains have been investigated by sugar and methylation analysis before and after removal of N-acetylneuraminic acid residues [17].
• The majority of the resulting clones had a phenotype not previously described for WGA-resistant CHO mutants arising spontaneously or from chemical mutagenesis: Neu5Ac was almost completely replaced by Neu5Gc [14].
• Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool [18].

Anatomical context of N-acetylneuraminic acid

• In mouse germinal center B cells, the expression of the GL7 epitope was upregulated due to the in situ repression of CMP-Neu5Ac hydroxylase (Cmah), the enzyme responsible for Sia modification of Neu5Ac to Neu5Gc [19].
• This showed that N-acetylneuraminic acid is the predominant saccharide at the nonreducing terminus of plasma membrane glycoproteins and that galactose and/or N-acetylgalactosamine residues are penultimate to these [20].
• Free N-acetylneuraminic acid, GM1, GM2, GD1a, and a mixture of bovine brain gangliosides containing GD1a and GT1b did not affect growth of K562 cells or show morphological changes [21].
• E-, P-, and L-selectin support the adhesion of leukocytes to the vessel wall through the recognition of specific carbohydrate ligands, which often contain sialylated, fucosylated lactosamines such as sialyl Lewis x [sLex; Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-] [22].
• LacCer and Cer from [stearoyl-14C]GM3 catabolism were found to accumulate in Salla fibroblasts, an indication that the enzymes of glycosphingolipid metabolism were affected by the impairment of Neu5Ac egress from lysosomes [23].

Associations of N-acetylneuraminic acid with other chemical compounds

• Adhesion is mediated by a carbohydrate-binding protein and can be inhibited by N-acetylneuraminic acid or mucin, a glycoprotein with high sialic acids content [24].
• Low concentrations of deoxycholate and incubation in 0.25 M sucrose solution liberated a small amount of microsomal sialoprotein and this fraction exhibited a high degree of labeling of protein-bound N-acetylneuraminic acid [25].
• Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in fibroblasts of patients with infantile free sialic acid storage disease [26].
• In vitro the human enzyme uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of Neu5Ac and KDN, respectively, but exhibits much higher activity toward the Neu5Ac phosphate product [27].
• Biochemical analysis showed that the mutant cells contained less than 5% of the cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuAc) present in parental CHO cells (1.6 nmol/mg of cell protein) [28].

Gene context of N-acetylneuraminic acid

• Two Neanderthal fossils studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH mutation predated the common ancestor of humans and the Neanderthal, approximately 0.5-0.6 million years ago (mya) [29].
• A known evolutionary difference is the strong preference of mouse siglec-2 (CD22) for Neu5Gc, contrasting with human siglec-2, which binds Neu5Ac equally well [30].
• The receptor on injured tracheal cells contains n-acetylneuraminic acid as the principal sugar, but the structure of the receptor in mucin has not been described [31].
• N-acetylneuraminic acid coupled human recombinant TNFalpha exhibits enhanced anti-tumor activity against Meth-A fibrosarcoma and reduced toxicity [32].
• Cells engineered to express MAG on their surface adhered specifically to gangliosides bearing an alpha 2,3-linked N-acetylneuraminic acid on a terminal galactose, with the following relative potency: GQ1b alpha >> GD1a, GT1b >> GM3, GM4 (GM1, GD1b, GD3, and GQ1b did not support adhesion) [33].

Analytical, diagnostic and therapeutic context of N-acetylneuraminic acid

• Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside [34].
• Volume of total mixed saliva and concentration of bicarbonate and N-acetylneuraminic acid during esophageal perfusion with water were higher in patients with reflux esophagitis than in age- and sex-matched controls and were similar to the values found in young healthy volunteers [3].
• "French type" sialuria, a presumably dominant disorder that, until now, had been documented in only five patients, manifests with mildly coarse facies, slight motor delay, and urinary excretion of large quantities (>1 g/d) of free N-acetylneuraminic acid (NeuAc) [35].
• The analysis of serum and liver glycoproteins by an ELISA type assay, using the lectin from Sambucus nigra (SNA) as a probe, revealed the presence of increased levels of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing transgenic mice as compared to controls [36].
• Western blotting of serum and liver proteins with radiolabeled SNA showed that all glycoproteins that bind the lectin in controls exhibit larger amounts of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing mice [36].

References