It fulfills a structural function in the bacterial cell wall, providing structural resistance and counteracting the osmotic pressure of the cytoplasm.
Peptidoglycan, also known as murein , is a polymer consisting of sugars and amino acids that form a mesh-like layer outside the plasma membrane of most bacteria, forming the cell wall.
The sugar component consists of alternating residues of N-acetylglucosamine (NAG) linked to β- (1,4) and N-acetylmuramic acid (NAM).
Attached to N-acetylmuramic acid is a peptide chain of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another chain that forms the three-dimensional mesh-like layer.
A common misconception is that peptidoglycan gives the cell its shape; however, while peptidoglycan helps maintain the structural strength of the cell, it is actually the MreB protein that facilitates the cell’s shape.
Peptidoglycan is also involved in binary fission during the reproduction of bacterial cells.
Therefore, the presence of high levels of peptidoglycan is the main determinant of the characterization of bacteria as Gram-positive.
In Gram-positive strains, it is important in the attachment roles and in the determination of the serotype. For Gram-positive and Gram-negative bacteria, particles of about 2 nm can pass through the peptidoglycan.
The peptidoglycan layer in the bacterial cell wall is a crystal lattice structure formed from linear chains of two alternative amino sugars, namely N-acetylglucosamine (GlcNAc or NAGA) and N-acetylmuramic acid (MurNAc or NAMA).
Alternating sugars are connected by a β- (1,4) -glycosidic bond.
Peptidoglycan is one of the most important sources of D-amino acids in nature.
Crosslinking between amino acids in different linear amino sugar chains occurs with the help of the enzyme DD-transpeptidase and results in a three-dimensional structure that is strong and rigid.
The specific amino acid sequence and molecular structure vary with bacterial species.
In the first step of peptidoglycan synthesis, glutamine, which is an amino acid, donates an amino group to a sugar, fructose 6-phosphate.
In step two, an acetyl group is transferred from acetyl CoA to the amino group on glucosamine-6-phosphate creating N-acetyl-glucosamine-6-phosphate.
In step three of the synthesis process, N-acetyl-glucosamine-6-phosphate is isomerized, which will change N-acetyl-glucosamine-6-phosphate to N-acetyl-glucosamine-1-phosphate.
In step 4, N-acetyl-glucosamine-1-phosphate, which is now a monophosphate, attacks Uridine-5′-triphosphate (UTF). Uridine triphosphate, which is a pyrimidine nucleotide, has the ability to act as an energy source.
In this particular reaction, after the monophosphate has attacked the Uridine-5′-triphosphate, an inorganic pyrophosphate is released and replaced by the monophosphate, creating UDP-N-acetylglucosamine (2,4).
When Uridine diphosphateUDP is used as an energy source, it emits an inorganic phosphate. This initial stage is used to create the N-acetylglucosamine precursor in peptidoglycan.
In step 5, part of the UDP-N-acetylglucosamine (UDP-GlcNAc) is converted to UDP-MurNAc (UDP-N-acetylmuramic acid) by adding a lactyl group to glucosamine.
This creates what is called an enol derivative that will be reduced to a “lactyl residue” by nicotinamide adenine dinucleotide phosphate (NADF) in step six.
In step 7, UDP-MurNAc is converted to UDP-MurNAc pentapeptide by the addition of five amino acids, which generally include the D-alanyl-D-alanine dipeptide.
Each of these reactions requires the energy source adenosine triphosphate (ATP). This is known as Stage One.
The second stage occurs in the cytoplasmic membrane.
Bactoprenol will attack the UDP-MurNAc penta, creating a PP-MurNac penta, which is now a lipid.
UDP-GlcNAc is then transported to MurNAc, creating Lipid-PP-MurNAc penta-GlcNAc, a disaccharide, also a peptidoglycan precursor. It is not yet understood how this molecule is transported across the membrane.
However, once it’s there, it adds to the growing glycan chain. The next reaction is known as tranglycosylation.
For a bacterial cell to reproduce through binary fission, more than one million peptidoglycan subunits (NAM-NAG + oligopeptide) must bind to existing subunits.
Mutations in genes encoding transpeptidases that lead to reduced interactions with an antibiotic are an important source of emerging antibiotic resistance.
Lysozyme, which is found in tears and is part of the body’s innate immune system, exerts its antibacterial effect by breaking the β- (1,4) -glycosidic bonds in peptidoglycan.
Similarity to pseudopeptidoglycan
Some archaea have a similar layer of pseudopeptidoglycan (also known as pseudomurein), in which the sugar residues are N-acetylglucosamine β- (1,3) and N-acetyl-aminosuronic acid.
This renders the cell walls of such archaea insensitive to lysozyme.