Review of Pharmacology - 9E (2015)

Review of Pharmacology
Bacterial cell wall is composed of peptidoglycan that contains N-acetylmuramic acid and
N-acetylglucosamine. It also contains a pentapeptide unit which is attached to N-acetylmuramic
acid. Cell wall synthesis starts by conversion of UDP-N-acetylglucosamine (UDP-G) to
UDP-N-acetylmuramic acid (UDP-M) in the presence of enzyme enolpyruvate transferase.
UDP-M then acquires the pentapeptide. Alanine racemase and alanine-alanine ligase helps
in the formation of pentapeptide unit. UDP is then removed from UDP-M-pentapeptide by
bactoprenol (membrane lipid carrier) and N-acetylglucosamine is added to it (which is carried
by UDP-G). These all reactions occur in the cytoplasm. The resulting molecule formed is
transported across the plasma membrane by bactoprenol. Elongation of the peptidoglycan
chain occurs with the help of enzyme transglycosylase. Strength to peptidoglycan
chain is provided by cross linking of elongated chains with the help of transpeptidase.
Various antibiotics can act by inhibiting one of these steps in cell wall synthesis as shown
in Table 13.1 below. All of these are bactericidal drugs.
Table 13.1: Mechanism of action of cell wall synthesis inhibiting antimicrobial drugs
Chemotherapy A: General Considerations and Non-specific...
Drug
Step in cell wall synthesis inhibited
Firmly Fosfomycin Enolpyruvate transferase
Bind to Beta lactam antibiotics Transpeptidase
Bacterial Bacitracin Dephosphorylation of bactoprenol
Cell Cycloserine Alanine racemase and alanine ligase
Vall Vancomycin Transglycosylase
B. Drugs Inhibiting Translation (Protein Synthesis)
Protein synthesis in the bacteria is accomplished with the use of 70S ribosome, mRNA and
tRNA. 70S ribosome consists of two subunits 30S and 50S. Latter (50S subunit) contains two
sites; A site (acceptor) and P site (peptidyl). Nascent (already formed) peptide chain is attached
to P site. Next amino acid is transported to the A site by tRNA having complementary base
pairs (anticodons). Peptide bond forms between the peptide chain and the newly attached
amino acid with the help of enzyme peptidyl transferase. The nascent peptide chain is thus
shifted from P site to A site. For further elongation of the peptide chain, A site must be free
because the next amino acid attaches to A site only. This is carried out by translocation of the
peptide chain from A site to P site. Ribosome moves forward along the mRNA to expose the
next codon. All of these steps keep on repeating till there is a termination codon on the mRNA
(at this point protein synthesis stops). All drugs inhibiting protein synthesis are bacteriostatic
except aminoglycosides and streptogramins.
Fig. 13.2: Steps of protein synthesis and the mechanism of action of drugs
Table 13.2: Mechanism of action of protein synthesis inhibiting antimicrobial drugs
514
Drugs Binds to Mechanism of action
1. Aminoglycosides Several sites at 30 S and 50
S subunits as well as to their
interface
• Freezing of initiation
• Interference with polysome formation
• Misreading of mRNA code
contd...
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