Antibacterials - DNA Flashcards
List some enzymes responsible for bacterial DNA replication.
DNA Helicase, DNA Polymerase III, Primase, DNA Polymerase I, Topoisomerase I, Topoisomerase II, Topoisomerase III, Topoisomerase IV.
What does DNA Helicase do?
Promotes strand separation at the replication fork.
What does DNA Polymerase III do?
The primary enzyme of replication; attaches nucleotides to the growing DNA chain and proofreads.
What does Primase do?
Makes short RNA primers for lagging strand.
What does DNA Polymerase I do?
Fills in gaps on lagging strand and removes RNA primers.
What does Topoisomerase I do?
Relax supercoiled DNA.
What does Topoisomerase II (DNA Gyrase) do?
Promotes negative supercoiling, maintains the shape of a chromosome.
What does Topoisomerase III do?
Removes negative supercoiling.
What does Topoisomerase IV do?
Similar function to II, removes knots and links behind replication fork.
How do metronidazole and nitrofurantoin work to target bacterial DNA synthesis?
The activated forms are cytotoxic and can interact with the DNA molecule through inhibiting DNA synthesis and DNA damage by oxidation. Oxidation causes single and double-strand breaks which eventually leads to DNA degradation and cell death.
How does rifampin work to inhibit bacterial DNA synthesis?
It specifically inhibits bacterial RNA polymerase (responsible for DNA transcription) by forming a stable drug-enzyme complex.
How do the quinolones act to inhibit DAN gyrase hence inhibiting bacterial DNA synthesis?
DNA gyrase works to maintain the proper coiling of DNA strands in the chromosome. Quinolones block re-sealing of bacterial DNA strands on supercoiling causing the bacterial chromosomes to break into multiple fragments.
What functional groups in the quinolone molecule are responsible for these drugs’ action in preventing bacterial DNA synthesis?
The carboxyl and carbonyl groups of the quinolones are important for their action.