N-Acetylneuraminic acid

Last updated
N-Acetylneuraminic acid
Neu5Ac in neutral form, 2C5 conformation.png
Names
IUPAC name
5-(acetylamino)-3,5-dideoxy-D-glycero-α-D-galacto-non-2-ulopyranosonic acid
Other names
  • NANA
  • Neu5Ac
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.004.568 OOjs UI icon edit-ltr-progressive.svg
MeSH N-Acetylneuraminic+Acid
PubChem CID
UNII
  • InChI=1S/C11H19NO9/c1-4(14)12-7-5(15)2-11(20,10(18)19)21-9(7)8(17)6(16)3-13/h5-9,13,15-17,20H,2-3H2,1H3,(H,12,14)(H,18,19)/t5-,6+,7+,8+,9+,11+/m0/s1 Yes check.svgY
    Key: SQVRNKJHWKZAKO-YRMXFSIDSA-N Yes check.svgY
  • InChI=1/C11H19NO9/c1-4(14)12-7-5(15)2-11(20,10(18)19)21-9(7)8(17)6(16)3-13/h5-9,13,15-17,20H,2-3H2,1H3,(H,12,14)(H,18,19)/t5-,6+,7+,8+,9+,11+/m0/s1
    Key: SQVRNKJHWKZAKO-YRMXFSIDBI
  • OC(=O)[C@@]1(O)C[C@H](O)[C@@H](NC(C)=O)[C@@H](O1)[C@H](O)[C@H](O)CO
Properties
C11H19NO9
Molar mass 309.273 g/mol
AppearanceWhite crystalline powder
Melting point 186 °C (367 °F; 459 K) (decomposes)
Pharmacology
M09AX05 ( WHO )
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

N-Acetylneuraminic acid (Neu5Ac or NANA) is the predominant sialic acid found in human cells, and many mammalian cells. Other forms, such as N-Glycolylneuraminic acid, may also occur in cells.

Contents

This residue is negatively charged at physiological pH and is found in complex glycans on mucins and glycoproteins found at the cell membrane. Neu5Ac residues are also found in glycolipids, known as gangliosides, a crucial component of neuronal membranes found in the brain.

Along with involvement in preventing infections (mucus associated with mucous membranes—mouth, nose, GI, respiratory tract), Neu5Ac acts as a receptor for influenza viruses, allowing attachment to mucous cells via hemagglutinin (an early step in acquiring influenzavirus infection).

In the biology of bacterial pathogens

Neu5Ac is also important in the biology of a number of pathogenic and symbiotic bacteria [1] [2] [3] as it can be used either as a nutrient, providing both carbon and nitrogen to the bacteria, or in some pathogens, can be activated and placed on the cell surface. [1] Bacteria have evolved transporters for Neu5Ac to enable them to capture it from their environment and a number of these have been characterized including the NanT protein from Escherichia coli , [4] the SiaPQM TRAP transporter from Haemophilus influenzae [5] and the SatABCD ABC transporter from Haemophilus ducreyi . [6]

See also

Related Research Articles

<span class="mw-page-title-main">Gram-negative bacteria</span> Group of bacteria that do not retain the Gram stain used in bacterial differentiation

Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is their cell envelopes, which consists of a thin peptidoglycan cell wall sandwiched between an inner (cytoplasmic) membrane and an outer membrane. These bacteria are found in all environments that support life on Earth.

<span class="mw-page-title-main">Pseudomonadota</span> Phylum of Gram-negative bacteria

Pseudomonadota is a major phylum of Gram-negative bacteria. The renaming of several prokaryote phyla in 2021, including Pseudomonadota, remains controversial among microbiologists, many of whom continue to use the earlier name Proteobacteria, of long standing in the literature. The phylum Proteobacteria includes a wide variety of pathogenic genera, such as Escherichia, Salmonella, Vibrio, Yersinia, Legionella, and many others. Others are free-living (non-parasitic) and include many of the bacteria responsible for nitrogen fixation.

<span class="mw-page-title-main">Haemophilus ducreyi</span> Species of gram-negative, pathogenic bacterium

Haemophilus ducreyi are fastidious gram-negative coccobacilli bacteria.

<span class="mw-page-title-main">Sialic acid</span> Class of chemical compounds

Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is N-acetylneuraminic acid found in animals and some prokaryotes.

<i>Haemophilus influenzae</i> Species of bacterium

Haemophilus influenzae is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria are mesophilic and grow best at temperatures between 35 and 37 °C.

<span class="mw-page-title-main">Bacterial capsule</span> Polysaccharide layer that lies outside the cell envelope in many bacteria

The bacterial capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.

<i>Haemophilus</i> Genus of bacteria

Haemophilus is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While Haemophilus bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of the wide range of shapes they occasionally assume. These organisms inhabit the mucous membranes of the upper respiratory tract, mouth, vagina, and intestinal tract. The genus includes commensal organisms along with some significant pathogenic species such as H. influenzae—a cause of sepsis and bacterial meningitis in young children—and H. ducreyi, the causative agent of chancroid. All members are either aerobic or facultatively anaerobic. This genus has been found to be part of the salivary microbiome.

<span class="mw-page-title-main">Bacterial outer membrane</span> Plasma membrane found in gram-negative bacteria

The bacterial outer membrane is found in gram-negative bacteria. Its composition is distinct from that of the inner cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and in some bacteria such as E. coli it is linked to the cell's peptidoglycan by Braun's lipoprotein.

The bacterium, despite its simplicity, contains a well-developed cell structure which is responsible for some of its unique biological structures and pathogenicity. Many structural features are unique to bacteria and are not found among archaea or eukaryotes. Because of the simplicity of bacteria relative to larger organisms and the ease with which they can be manipulated experimentally, the cell structure of bacteria has been well studied, revealing many biochemical principles that have been subsequently applied to other organisms.

<span class="mw-page-title-main">Efflux (microbiology)</span> Protein complexes that move compounds, generally toxic, out of bacterial cells

In microbiology, efflux is the moving of a variety of different compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.

<span class="mw-page-title-main">DsrA RNA</span> Non-coding RNA

DsrA RNA is a non-coding RNA that regulates both transcription, by overcoming transcriptional silencing by the nucleoid-associated H-NS protein, and translation, by promoting efficient translation of the stress sigma factor, RpoS. These two activities of DsrA can be separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is necessary for RpoS translation but not for anti-H-NS action, while the second stem-loop is essential for antisilencing and less critical for RpoS translation. The third stem-loop, which behaves as a transcription terminator, can be substituted by the trp transcription terminator without loss of either DsrA function. The sequence of the first stem-loop of DsrA is complementary with the upstream leader portion of RpoS messenger RNA, suggesting that pairing of DsrA with the RpoS message might be important for translational regulation. The structures of DsrA and DsrA/rpoS complex were studied by NMR. The study concluded that the sRNA contains a dynamic conformational equilibrium for its second stem–loop which might be an important mechanism for DsrA to regulate the translations of its multiple target mRNAs.

<span class="mw-page-title-main">CMAH</span> Pseudogene in the species Homo sapiens

Cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah) is an enzyme that is encoded by the CMAH gene. In most mammals, the enzyme hydroxylates N-acetylneuraminic acid (Neu5Ac), producing N-glycolylneuraminic acid (Neu5Gc). Neu5Ac and Neu5Gc are mammalian glycans that compose the glycocalyx, especially in sialoglycoproteins, which are part of the sialic acid family. The CMAH equivalent in humans is a pseudogene (CMAHP); there is no detectable Neu5Gc in normal human tissue. This deficiency has a number of proposed effects on humans, including increased brain growth and improved self-recognition by the human immune system. Incorporation of Neu5Gc from red meat and dairy into human tissues has been linked to chronic disease, including type-2 diabetes and chronic inflammation.

<span class="mw-page-title-main">Pathogenic bacteria</span> Disease-causing bacteria

Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of these pathogenic species in humans is estimated to be fewer than a hundred. By contrast, several thousand species are part of the gut flora present in the digestive tract.

<i>N</i>-Glycolylneuraminic acid Chemical compound

N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid molecule found in most non-human mammals. Humans cannot synthesize Neu5Gc because the human gene CMAH is irreversibly mutated, though it is found in other apes. The gene CMAH encodes for CMP-N-acetylneuraminic acid hydroxylase, which is the enzyme responsible for CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid. This loss of CMAH is estimated to have occurred 2-3 million years ago, just before the emergence of the genus Homo.

Tripartite ATP-independent periplasmic transporters are a large family of solute transporters found in bacteria and archaea, but not in eukaryotes, that appear to be specific for the uptake of organic acids or related molecules containing a carboxylate or sulfonate group. They are unique in that they utilize a substrate binding protein (SBP) in combination with a secondary transporter.

<span class="mw-page-title-main">Trimeric autotransporter adhesin</span> Proteins found on the outer membrane of Gram-negative bacteria

In molecular biology, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs also go by another name, oligomeric coiled-coil adhesins, which is shortened to OCAs. In essence, they are virulence factors, factors that make the bacteria harmful and infective to the host organism.

<span class="mw-page-title-main">YadA bacterial adhesin protein domain</span>

In molecular biology, YadA is a protein domain which is short for Yersinia adhesin A. These proteins have strong sequence and structural homology, particularly at their C-terminal end. The function is to promote their pathogenicity and virulence in host cells, though cell adhesion. YadA is found in three pathogenic species of Yersinia, Y. pestis,Y. pseudotuberculosis, and Y. enterocolitica. The YadA domain is encoded for by a virulence plasmid in Yersinia, which encodes a type-III secretion (T3S) system consisting of the Ysc injectisome and the Yop effectors.

The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.

N-glycosyltransferase is an enzyme in prokaryotes which transfers individual hexoses onto asparagine sidechains in substrate proteins, using a nucleotide-bound intermediary, within the cytoplasm. They are distinct from regular N-glycosylating enzymes, which are oligosaccharyltransferases that transfer pre-assembled oligosaccharides. Both enzyme families however target a shared amino acid sequence asparagine—-any amino acid except proline—serine or threonine (N–x–S/T), with some variations.

References

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  2. Vimr, Eric R.; Kalivoda, Kathryn A.; Deszo, Eric L.; Steenbergen, Susan M. (March 2004). "Diversity of Microbial Sialic Acid Metabolism". Microbiology and Molecular Biology Reviews. 68 (1): 132–153. doi:10.1128/MMBR.68.1.132-153.2004. ISSN   1092-2172. PMC   362108 . PMID   15007099.
  3. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM (2004). "Diversity of microbial sialic acid metabolism". Microbiol Mol Biol Rev. 68 (1): 132–153. doi:10.1128/mmbr.68.1.132-153.2004. PMC   362108 . PMID   15007099.
  4. Vimr ER, Troy FA (1985). "Identification of an inducible catabolic system for sialic acids (nan) in Escherichia coli". J. Bacteriol. 164 (2): 845–853. doi:10.1128/jb.164.2.845-853.1985. PMC   214328 . PMID   3902799.
  5. Severi E, Randle G, Kivlin P, Whitfield K, Young R, Moxon R, Kelly D, Hood D, Thomas GH (2005). "Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter". Mol. Microbiol. 58 (4): 1173–1185. doi: 10.1111/j.1365-2958.2005.04901.x . PMID   16262798. S2CID   32085592.
  6. Post DM, Mungur R, Gibson BW, Munson RS Jr (2005). "Identification of a novel sialic acid transporter in Haemophilus ducreyi". Infect Immun. 73 (10): 6727–35. doi:10.1128/IAI.73.10.6727-6735.2005. PMC   1230923 . PMID   16177350.