Enlist Any Two Inhibitors of Nucleotide Synthesis With Their Mechanism of Action, Enzyme Inhibited, and Their Use in Medicine
Nucleotide synthesis inhibitors are crucial in medicine, particularly in cancer therapy, autoimmune diseases, and transplant medicine. Here are two well-known inhibitors:
1. Methotrexate
- Mechanism of Action: Methotrexate is a folate analog that inhibits dihydrofolate reductase (DHFR), an enzyme required to regenerate tetrahydrofolate (THF), a coenzyme essential for purine and thymidylate synthesis.
- Enzyme Inhibited: Dihydrofolate reductase (DHFR)
- Medical Use:
- Used in treatment of cancers such as leukemia, breast cancer, and osteosarcoma
- Also used as an immunosuppressant in rheumatoid arthritis and psoriasis
2. 5-Fluorouracil (5-FU)
- Mechanism of Action: 5-FU is converted into 5-fluoro-deoxyuridine monophosphate (FdUMP), which inhibits thymidylate synthase, blocking the synthesis of dTMP from dUMP. This leads to a depletion of thymidine nucleotides necessary for DNA replication.
- Enzyme Inhibited: Thymidylate synthase
- Medical Use:
- Used to treat various cancers including colorectal, breast, and gastric cancer
These inhibitors selectively target rapidly dividing cells by blocking DNA synthesis, making them effective anticancer agents, though they also affect normal proliferating cells.