FOLIC ACID ANTAGONISTS Introduction to Folie Acid: Folic acid, also known as vitamin B9, plays a crucial role in DNA synthesis, repair, and cell division. Itis necessary for the formation of red blood cells and the proper development of the nervous system. Folic acid is obtained through dietary sources or can be taken as a supplement. Formation of tetrahydro folic acid & mechanism of action of sulfonamides and methotrexate: DHPA (dihydropteroic acid) is formed through a condensation reaction between p- aminobenzoic acid (PABA) and pteridine, through an enzyme dihydropteroate synthase (DHPS).(sulfonamides are structural analogs of PABA so target the enzyme DHPS) DHPA is further processed to dihydrofolic acid (DHF) through the action of the enzyme dihydrofolate synthase (DHFS). ‘The enzyme dihydrofolate reductase (DHFR) converts DHF to THF.(methotrexate inhibit DHFR) THF is the biologically active form of folic acid and plays a critical role in various cellular processes, including DNA and RNA synthesis, amino acid metabolism, and methylation reactions. Clinical Applications: Folic acid antagonists find wide application in chemotherapy, particularly for the treatment of cancer. Methotrexate, one of the most commonly used folic acid antagonists, is used in the treatment of various cancers, such as Ieukemia, lymphoma, and solid tumors. These drugs inhibit the rapid cell division and growth characteristic of cancer cells by interfering with folate metabolism. « ° y A gaubinmune divest (pernes, Potential Side Effects: Folic acid antagonists can affect normal, healthy cells that also rely on foat for ther proper functioning. Side effects can include gastrointestinal disturbances, bone marow suppression, and an k en Fe ‘hentse due to lowered immunity, Or me hot er” + pHPS., D’bydve DFS. pHeg DHFR THE Previdime, eee (rete ry ) ehe ferwr pens taking folie acid antagonists often require supplementation with folinic :UCOVORIN), a derivative of THF, to mitigate these side effects. aa Folic acid antagonists are also employed in the treatment of certain autoims such as rheumatoid arthritis and psoriasis. These drugs can help modulate the immune response and reduce inflammation, mune disorders, Importance of Folate Supplementation: Folate supplementation helps prevent neural tube defects in developing fetuses and supports overall health, —_—___ Consequences of Folate Depletion: Folate is essential for the synthesis of thymidine, which is required for DNA replication. ‘As aresult, cells, particularly rapidly dividing ones like cancer cells, experience reduced growth and replication. Selective Toxicity in Cancer Cells: Folic acid antagonists exploit the fact that cancer cells exhibit higher rates of cell division and DNA synthesis compared to normal cells. ‘The decreased availability of THF selectively affects the proliferation of cancer cells, leading to their inhibition or death. Normal cells, on the other hand, are often able to obtain sufficient folate through alternative metabolic pathways, reducing their susceptibility tothe effects of folic acid antagonists. eee ese SUMMARY, folic acid antagonists inhibit the enzyme DHFR, leading to a depletion of intracellular folate levels. They find applications in chemotherapy and the treatment of ‘autoimmune disorders. On the other hand, sulfonamides target the enzyme DHPS, interfering with folate synthesis in bacteria and are commonly used as antibiotics. Both drug classes disrupt folate metabolism, but their mechanisms of action and clinical applications differ. Pteroic acid is converted into dihydropteroic acid (DHPA) through the action of the enzyme dihydropteroate synthase (DHPS), and subsequently, DHPA is further processed to form THF.