BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

PART V. MOLECULAR PHYSIOLOGY

CHAPTER 32. BACTERIAL CELL WALLS

32.2. Stages of Peptidoglycan Synthesis

Peptidoglycan synthesis occurs in five stages.

1. A peptide unit is assembled on the NAM residue attached to uridine diphosphate.

2. The resulting NAM-peptide unit is transferred to a lipid carrier. The Significance of this stage for Cell wall synthesis is as follows. The final polymerized product is located outside The Cell (on the outer side of the cell permeability barrier), whereas its precursor is synthesized inside the cell. UDP, being a polar compound, cannot cross The cell membrane. The lipid carrier, however, as a completely nonpolar compound, is capable of shuttle movements across the membrane.

Class="center">Fig. 32.4. Schematic representation of peptidoglycan. Sugars are shown in yellow, tetrapeptides in red, and pentaglycine bridges in blue. Due to the Abundance of cross-links, The cell wall forms a single giant sacculus macromolecule

3. NAG and a pentaglycine bridge are added to the NAM-peptide unit linked to the lipid carrier.

4. The resulting disaccharide-peptide unit is transferred from the lipid carrier to the growing polysaccharide chain.

5. Individual polysaccharide chains are cross-linked by pentaglycine bridges through a transpeptidation reaction.

32.3. Synthesis of the UDP-Carbohydrate-Peptide Unit

The Biosynthesis of peptidoglycans begins with The formation of activated sugars. Uridine diphosphate-N-acetylglucosamine (UDP-NAG) is synthesized from N-acetylglucosamine-1-phosphate and UTP in a reaction driven by the Hydrolysis of a pyrophosphate bond (Fig. 32.5). Uridine diphosphate-N-acetylmuramic acid (UDP-NAM) is formed from UDP-NAG and phosphoenolpyruvate (Fig. 32.6).

Fig. 32.5. Synthesis of UDP-NAG

Fig. 32.6. Synthesis of UDP-NAM

Peptide chain elongation begins with the formation of a peptide bond between the amino group of L-Alanine and the carboxyl group of the N-acetylmuramic acid residue in UDP-NAM. D-glutamate, L-Lysine, and the dipeptide D-alanyl-D-alanine are then added sequentially (Fig. 32.7). D-Amino Acids are formed from their corresponding L-isomers by the action of racemases containing Pyridoxal phosphate as a prosthetic group. The formation of each of these peptide bonds is powered by ATP energy. It should be emphasized that synthesis in this case is not carried out via the standard mechanism of ribosomal Protein Synthesis, but rather by specialized Enzymes. Consequently, the information regarding the Amino Acid Sequence is determined solely by the Specificity of the enzymes, rather than by The nucleotide sequence of Messenger RNA. A peptide of this type could not be synthesized in the conventional way on Ribosomes because it incorporates D-Amino Acids and a γ-peptide bond.

Fig. 32.7. Synthesis of the pentapeptide on UDP-NAM

32.4. Transfer of the Carbohydrate-Peptide Unit to the Lipid Carrier

In the next step, the activated carbohydrate-peptide unit is transferred from UDP to the lipid carrier (Fig. 32.8). The latter is a long-chain alcohol containing 11 isoprene units and is therefore highly hydrophobic, in contrast to UDP. Apparently, it is precisely due to the hydrophobic nature of this C₅₅-lipid that the newly formed carbohydrate-peptide unit overcomes the permeability barrier posed by the cell membrane.

Fig. 32.8. Structure OF THE lipid carrier involved in cell wall biosynthesis

Recall that another highly hydrophobic carrier—dolichol phosphate—is involved in the synthesis of the oligosaccharide core (the oligosaccharide "core") of Glycoproteins in eukaryotes (Section 29.31).