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Enzymes responsible for nucleotide synthesis comprise a diverse group essential for the production of purines and pyrimidines—the building blocks of DNA and RNA. These pathways are divided into de novo biosynthesis routes that assemble nucleotides from small molecules and salvage pathways that recycle bases from degraded nucleic acids. Key examples include dihydrofolate reductase and thymidylate synthase in pyrimidine biosynthesis; inosine monophosphate dehydrogenase in purines; ribonucleotide reductases convert ribonucleotides into deoxyribonucleotides required for DNA replication. Because proliferating cells require abundant nucleotides—especially cancerous or immune cells—these enzymes are major therapeutic targets across oncology, immunology, virology, and rare metabolic diseases. Inhibitors such as methotrexate or fluorouracil disrupt cell division by blocking critical enzymatic steps but may also cause significant side effects due to their impact on normal proliferating tissues.
Mechanisms by which drugs act on these enzymes include: - Competitive inhibition of key synthetic steps in purines/pyrimidines (e.g., methotrexate inhibits folic acid pathway via dihydrofolate reductase; fluorouracil inhibits thymidylate synthase)
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