Disease relevance of N-acetylneuraminic acid

• We have identified a sialate O-acetyltransferase in the lipo-oligosaccharide biosynthesis locus of Campylobacter jejuni [1].
• Here we show that ManNAc-6-phosphate (ManNAc-6-P) is not an obligate sialate precursor in Escherichia coli K1 [2].
• A sialate aldolase (pm1715) mutant unable to initiate dissimilation of internalized sialic acid was not attenuated in the CD-1 mouse model of systemic pasteurellosis, indicating that the nutritional function of sialate catabolism is not required for systemic disease [3].
• Sialate 9(4)-O-acetylesterases (EC 3.1.1.53) have been isolated from equine liver, bovine brain and influenza C virus [4].
• Faecal extracts from ulcerative colitis (UC) patients had higher sialate O-acetyl esterase and glycosulfatase activity, while mucin sialidase activity was unchanged [5].

High impact information on N-acetylneuraminic acid

• Identification of a Sialate O-Acetyltransferase from Campylobacter jejuni: DEMONSTRATION OF DIRECT TRANSFER TO THE C-9 POSITION OF TERMINAL{alpha}-2, 8-LINKED SIALIC ACID [1].
• Unlike a cytosolic sialate: O-acetylesterase (CSE) with similar specificity, the LSE carries N-linked oligosaccharides [6].
• The combined results indicate that neither ManNAc-6-P nor specific or non-specific phosphatase are necessary to generate the requisite ManNAc for sialate biosynthesis [2].
• The combined results provide the first direct evidence of sialylation by a precursor scavenging mechanism in pasteurellae and of a potential tripartite ATP-independent periplasmic sialate transporter in any species [3].
• Comprehensive kinetic analysis of influenza hemagglutinin-mediated membrane fusion: role of sialate binding [7].

Biological context of N-acetylneuraminic acid

• The combined results demonstrate how E. coli avoids a futile cycle in which biosynthetic sialate induces the system for its own degradation and indicate the feasibility of generating sialooligosaccharide precursors through targeted manipulation of sialate metabolism [8].
• Genetic hybrids of nonpathogenic, sialate-negative laboratory Escherichia coli K-12 strains designed for the de novo synthesis of the polysialic acid capsule from E. coli K1 proved useful in elucidating the genetics and biochemistry of capsule biosynthesis [8].
• A high homology was found between the amino acid sequences of the sialate lyases from Clostridium perfringens and Haemophilus influenzae (75% identical amino acids) or Trichomonas vaginalis (69% identical amino acids), respectively, whereas the similarity to the gene from E. coli is low (38% identical amino acids) [9].
• Members of this fold include enzymes like deoxyuridine triphosphatase and the SET methylase, carbohydrate-binding domains like the fish antifreeze proteins/Sialate synthase C-terminal domains, and functionally enigmatic accessory subunits of urease and molybdopterin biosynthesis protein MoeA [10].

Anatomical context of N-acetylneuraminic acid

• Characterization of a sialate pyruvate-lyase in the cytosol of human erythrocytes [11].
• At the moment, the presence of sialate pyruvate-lyase in the cytosol of red blood cells remains an enigma [11].
• Fractionation of horse liver homogenate by centrifugation into heavy membranes at 10,000 x g, microsomal fraction at 105,000 x g, and the supernatant revealed sialate 9-O-lactoyltransferase activity only in the latter fraction [12].
• These results indicate that the reduction of the surface negative charging is demonstrated in toxemic syncytiotrophoblasts and appears to be secondary to the decrease in the amount of sialate [13].

Associations of N-acetylneuraminic acid with other chemical compounds

• Metabolic accumulation of CMP-sialic acid depended on a functional sialic acid synthase (neuB), as shown by the inability of a strain lacking this enzyme to accumulate a detectable endogenous sialate pool [8].
• Sialate lyase (sialate aldolase; systematic name N-acetylneuraminate pyruvate-lyase, EC 4.1.3.3) was isolated as soluble enzyme from pig kidney and purified 630-fold using a heating step, gel filtration, and chromatography on immobilized neuraminic acid beta-methyl glycoside in 14% yield to apparent homogeneity as tested by SDS-gel electrophoresis [14].

Gene context of N-acetylneuraminic acid

• Mucin degradation in the human colon: production of sialidase, sialate O-acetylesterase, N-acetylneuraminate lyase, arylesterase, and glycosulfatase activities by strains of fecal bacteria [15].
• The function of the sialate aldolase (encoded by nanA) in limiting intermediate flux through the synthetic pathway was determined by analyzing free sialate accumulation in neuA (CMP-sialic acid synthetase) nanA double mutants [8].
• Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS) [16].
• Kinetic analysis with methly umbelliferyl sialate (MU-Neu5Ac) gave KM and Vmax values of 0.17 mM and 0.84 mmol/min x mg protein respectively [17].
• Further, infection with C1 resulted in significant increases in serum sialic acid (SSA) concentrations, and splenomegaly, as well as body weight reduction [18].

References