folatsyntesen

Folatsyntesen, also known as folate synthesis or the folic acid synthesis pathway, refers to the biochemical process by which certain organisms produce folate, a vital B vitamin. This pathway is essential for many life forms, including bacteria, fungi, plants, and some protozoa, but notably absent in animals, including humans. This absence makes folate an essential nutrient for these organisms, requiring them to obtain it from their diet.

The de novo synthesis of folate is a complex, multi-step process. It begins with the condensation of a pyrimidine derivative, typically 2-amino-4-hydroxy-6-hydroxymethylpteridine, with para-aminobenzoic acid (PABA). This reaction, catalyzed by the enzyme dihydropteroate synthase (DHPS), forms dihydropteroate. Subsequently, dihydropteroate is conjugated with one or more glutamate residues by the enzyme dihydropteroate synthetase, resulting in the formation of dihydrofolate. Finally, dihydrofolate is reduced to tetrahydrofolate (THF) by dihydrofolate reductase (DHFR). THF is the metabolically active form of folate and serves as a crucial coenzyme in one-carbon transfer reactions. These reactions are indispensable for the synthesis of purines, pyrimidines, and certain amino acids, thereby playing a fundamental role in DNA synthesis, repair, and cell division.

The critical role of folatsyntesen in microbial life has made it a significant target for antimicrobial drugs. Antibiotics like sulfonamides function by competitively inhibiting DHPS, thereby blocking the synthesis of dihydropteroate and ultimately halting folate production in susceptible bacteria. Trimethoprim, another antibiotic, inhibits DHFR. By targeting these essential enzymes, these drugs effectively disrupt crucial metabolic pathways in bacteria, leading to their death or inhibition of growth. This selective inhibition allows for therapeutic intervention without significantly harming host cells, which do not possess the same synthetic pathway.