Table Of Contents
Tetrahydrofolate Synthesis
Tetrahydrofolate (THF) is essential for purine synthesis and thymidylate (dTMP) formation, both of which are important for DNA synthesis.
THF synthesis in Bacteria vs Humans
| Category | Description |
| Bacteria | Must synthesize folate de novo |
| Humans | Cannot synthesize folate de novo. Folate is obtained from the diet and is converted to DHF, which is then converted to THF via human DHFR |
Humans cannot synthesize folate de novo. Folate is obtained from the diet and is converted to DHF, which is then converted to THF via human DHFR.
- Clinical implications
- Sulfonamides: antibiotics that inhibit dihydropteroatesynthase. Humans lack dihydropteroate synthsase, hence are not affected by sulfonamides.
- Trimethoprim (TMP): antibiotic that inhibits bacterial DHFR. Has a lower affinity for human DHFR.
- Co-trimoxazole (TMP-SMX): blocks two sequential steps in bacterial folate synthesis
- Methotrexate: inhibits human DHFR causing toxicity in rapidly dividing human cells (cancer, autoimmune diseases, ectopic pregnancy etc.)
