Purine biosynthesis:

1. 1. Purines are synthesized using both de novo and salvage pathways.

2. The purine ring is built on a ribose skeleton to make IMP, followed by branches to AMP and GMP. Amino acids serve as N donors, while CO₂ and C1 units of N¹⁰ -formyl-THF are carbon donors.

3. The general mechanism involves ATP-mediated phosphorylation of carbonyl oxygen, followed by phosphate displacement by an amine.

4. Purine biosynthesis is tightly regulated via feedback inhibition. Formation of phosphoribosylamine is the committed step. The loss of regulation can lead to a clinical disease.

5. NAD⁺ is biosynthesized from nicotinate, ATP, and PRPP. Glutamine is used as an amino donor.

PEPTIDOGLYCAN SYNTHESIS:

Bacterial cell walls contain a large, complex peptidoglycan molecule consisting of log polysaccharide chains made of alternating N-acetykmuramic acid (NAM) and N-acetylglucosamine (NAG) residues. Pentapeptide chains are attached to the NAM groups. The polysaccharide chains are connected through their pentapeptides or by interbridges. Peptidoglycan synthesis is a multistep process that has been best studied in the gram-positive bacterium Staphylococcus aureus. Two carriers participate: uridine diphosphate (UDP) and bactoprenol. Bactoprenol is a 55-carbon alcohol that attaches to NAM by a pyrophosphate group and moves peptodoglycan components through the hydrophobic membrane. Transpeptidation is an important reaction, wherein finally peptide cross-links between peptidoglycan chains are formed. Peptidoglycan synthesis is particularly vulnerable to disruption by antimicrobial agents. Inhibition at any stage can weaken the cell wall and can lead to osmotic lysis. Many antibiotics interfere with peptidoglycan synthesis. For example, Penicillin inhibits the transpeptidation reaction and bacitracin blocks the dephosphorylation of bactoprenol pyrophosphate.

PATTERNS OF CELL WALL FORMATION:

To grow and divide efficiently, a bacterial cell must add new peptidoglycan to its cell wall in a precise and well-regulated way while maintaining wall shape and integrity in the presence of high osmotic pressure. The growing bacterium must be able to degrade it just enough to provide accept ends for the incorporation of new peptidoglycan units. It must also reorganize peptidoglycan structure when necessary. This limited peptidoglycan digestion is accomplished by enzymes known as autolysins, some of which attack the polysaccharide chains, while others hydrolyze the peptide cross-links. Autolysin inhibitors keep the activity of these enzymes under tight control.

There seems to be two general patterns of location and distribution of cell wall synthetic activity and varies with species. Many gram-positive cocci have only one to a few zones of growth. The principal growth zone is usually at the site of septum formation, and new cell wall halves are synthesized back-to-back. The second pattern of synthesis occurs in the rod shaped bacterial and occurs at the site of septum formation just as before, but growth sites also are scattered along the cylindrical portion of the rod. Thus growth is distributed more diffusely in rod-shaped bacteria than in the cocci. Synthesis must lengthen rod-shaped cells as well as divide them. Presumably this accounts for the differences in wall formation pattern.

REFERENCES:

Text Books:

1. Jeffery C. Pommerville. Alcamo's Fundamentals of Microbiology (Tenth Edition). Jones and Bartlett Student edition.

2. Gerard J. Tortora, Berdell R. Funke, Christine L. Case. Pearson - Microbiology: An Introduction. Benjamin Cummings.

Reference Books:

1. Lansing M. Prescott, John P. Harley and Donald A. Klein. Microbiology. Mc Graw Hill companies.