IV-Acetyl muramic acid

Lysozyme (see) destroys the cell wall structure of bacteria by hydrolysing 1,4-glycosidic linkages between C4 of iV-acetylglucosamine and Cl of iV-acetyl-muramic acid in M.The glycosidic bond between Cl of N-acetylglucosamine and C4 of N-acetylmuramic acid is not cleaved. The products of cleavage are muropeptides , e.g. 

Murein D-glciVAc-p, iV-acetyl-muramic acid, amino acids (1,4) Bacteria (cell wall)... 

Precursors of the peptidoglycan are UDP-iV-acetylglucosamine derived from iV-acetylglucosamine (D 1.1), and the peptide UDP-iV-acetylmuramyl-L-alanyl-D-glutamyl-L-lysyl (or diaminopimelyl)-D-alanyl-D-alanine formed from iV-acetyl-muramic acid. 

The pattern of cleavage of the cell wall of B. subtilis by purified iV-acetyl-muramic acid L-alanine amidase has been studied in the absence, and in the presence, of a modifier protein that combines stoicheiometrically with the enzyme to stimulate its activity. The modifier protein did not affect the rate of the enzymic reaction, but changed the mode of cleavage of the cell wall from a random pattern to a sequential pattern. Binding of the enzyme to the cell wall and functional interaction with the modifier protein occurred only when the cell wall contained teichoic acids. It appears that cell-wall teichoic acids act as specific allosteric ligands for bacterial lytic enzymes. 

The structure of the native immunostimulatory MDPs was found to be IV-acetyl muramyl-L-alanyl-D-isoglutamine. (/V-Acetyl muramic acid is a base component of bacterial peptidoglycan.) Native TDM is a potent pyrogen and is too toxic for general use as an adjuvant. The molecular basis underlining MDP s adjuvanticity remains to be fully elucidated. Administration of MDP, however, is known to activate a number of cell types that play direct/indirect roles in immune function, and induces the secretion of various immunomodulatory cytokines (Table 13.14). 

Lysozyme catalyzes the hydrolysis of a polysaccharide that is the major constituent of the cell wall of certain bacteria. The polymer is formed from /3( 1 —> 4)-linked alternating units of IV-acetylglucosamine (NAG) and N-acetyl-muramic acid (NAM) (Figure 1.25). The solution of the structure of lysozyme... 

Add (pick) saccharide residues from the list of aldoses (hexoses in al-dopyranose form, pentoses in aldofuranose form, and tetraoses in open-chain form), ketoses (hexoses in ketofuranose form, pentoses and tetraose in open-chain form), derivatives (glucosamine, galactosamine, N-acetylnuraminic acid, N-acetyl muramic acid, inositol, 2-deoxyribose, rhamnose, fucose, and apiose), and blocking groups (H, NH2, =0, COO—, methyl, lactyl, O-methyl, iV-methyl, O-acetyl, iV-acetyl, phosphoric acid, sulfate, iV-sulfonic acid) to build polysaccharides. 

A substance later shown to be muramic acid (see Section IV,6) was clearly different from the product of Vi antigen, and, although the strain used in some of the Vi studies (Escherichia coli 5396/38) is one in which sialic acid has been detected, the properties of the Vi antigen are markedly different from the neuraminic acid pol3oner. Infrared spectra recorded for crystalline V-acetyl-neuraminic acid exhibit full detail and cannot be compared with that published for aminohexuronic acid, but that of the amorphous neuraminic acid polymer (colominic acid) is rather similar to that of the Vi antigen polymeric unit, since their functional groups are very similar. The relationship of these substances to the property of 0 -inagglutinability is discussed later (see p. 336). 

There are several polysaccharides containing the /1-(1 4) stracture, but with monomer residues other than D-glucop)ranose, such as )V-acetyl-D-glucosamine, D-glucosamine, iV-acetyl-D-muramic acid. 

A large number of bacterial polysaccharides are known [104]. The major structural component of the bacterial cell wall is a polysaccharide, known as murein and composed of a repeating unit of one A-acetyl-D-glucosamine and an O-lactyl substituted IV-acetyl-D-glucosamine (A-acetyl-D-muramic acid) see Sect. 7.3. 

Variations also occur in the muramic acid itself. In S. aureus approximately half of the muramic acid residues bear an acetyl group on the 6 position. This modification renders the peptidoglycan insensitive to degradation by lysozyme. Similar modifications have been reported in some strains of Proteus, Neisseria and Pseudomonas. Loss of some of the iV-acetyl residues from the V-acetylglucosamine of some Bacillus cereus strains also has the effect of rendering the peptidoglycan resistant to lysozyme. 

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