Peptidoglycan

Peptidoglycan Structure

Peptidoglycan or murein is an enormous polymer of two sugar derivatives- N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) joined by β-1,4 glycosidic bond. A tetrapeptide i.e. a peptide chain of four alternating D- and L- amino acids is connected to the carboxyl group of NAM. The amino acid present in tetrapeptide includes L- alanine, D- glutamic acid, D- alanine and either L- lysine or meso-diaminopimelic acid (DAP). The three amino acids i.e. D- glutamic acid, D- alanine and DAP are not found in proteins and these D- amino acids provides protection against most of the peptidases. The two tetrapeptide chain lying side by side may be linked directly to each other (as seen in many Gram negative bacteria) or indirectly by a peptide interbridge of short chain amino acids (such as polyglycine). Peptide interbridge are generally observed in Gram positive bacteria and they helps to retain their shape and intergrity. This reaction of peptide cross link formation during peptidoglycan synthesis is known as transpeptidation.

Peptidoglycan Synthesis

The biosynthesis of peptidoglycan starts in the cytoplasm as monomer and then with the help of membrane carrier bactoprenol they get transported across the cell membrane and joins the existing peptidoglycan. Firstly, the synthesis of nucleotide sugar-linked precursors UDP-NAM (Uridine diphosphate- N-acetylmuramic acid) and UDP-NAG (UDP- N-acetylglucosamine) takes place. NAG with a lactic acid attached by ether linkage is NAM. Next, amino acids are added to UDP-NAM and NAM-pentapeptide is formed. Third step takes place in cytoplasmic membrane. Bactoprenol, a lipid carrier, is present in the cytoplasmic membrane. This bactoprenol attacks UDP-NAM-pentapeptide and forms lipid I which is PP-NAM-pentapeptide. This is followed by the addition of NAG from UDP-NAG to lipid I, resulting in lipid II (PP-NAM-pentapeptide-NAG, a disaccharide and a precursor to peptidoglycan). The last step, which takes place outside the cytoplasmic membrane, is basically the polymerization of newly synthesized disaccharide with the growing glycan chain. This reaction is known as transglycosylation and enzyme involved is called transglycosylase. Hydroxyl group of the NAG will attach to the NAM in the growing chain during transglycosylation and thereby displacing the lipid-PP from the glycan chain.