1. Different Enzymes:
* Humans: Humans obtain folic acid from their diet, and don't synthesize it. We rely on preformed folate.
* Bacteria: Bacteria synthesize their own folic acid through a series of enzymatic steps.
2. Drug Targets:
* Sulfonamides: These drugs competitively inhibit the bacterial enzyme dihydrofolate synthetase (DHFS). DHFS is responsible for converting para-aminobenzoic acid (PABA) to dihydrofolate, a precursor to tetrahydrofolate (THF).
* Trimethoprim: This drug inhibits the bacterial enzyme dihydrofolate reductase (DHFR), which converts dihydrofolate to tetrahydrofolate.
3. Selective Toxicity:
* Sulfonamides and trimethoprim target bacterial enzymes involved in folic acid synthesis.
* Humans do not synthesize folic acid and thus are not affected by these drugs.
* Bacterial enzymes differ significantly from their human counterparts, allowing for selective inhibition.
4. Consequences of Folic Acid Depletion:
* Bacteria: Depletion of THF in bacteria disrupts critical metabolic pathways like DNA, RNA, and protein synthesis, ultimately leading to cell death.
* Humans: Humans are not directly affected by the drugs, as they obtain folate from their diet and do not rely on the affected enzymes.
In summary, drugs that block folic acid synthesis achieve selective toxicity by targeting bacterial enzymes involved in folate synthesis, which are significantly different from their human counterparts. This allows for the effective treatment of bacterial infections while minimizing harm to the host.
