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Enzyme responsible for nucleotide synthesis

Molecular classification
Enzyme, Oxidoreductase (e.g., ribonucleotide reductase), Transferase (e.g., thymidylate synthase), Ligase (e.g., DNA ligase), Hydrolase (various nucleotidases)
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Overview

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.

Other names
Nucleotide biosynthesis enzymeNucleotide metabolism enzymePurine synthesis enzymePyrimidine synthesis enzyme
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Mechanism of action

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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Biological functions

DNA replicationRNA transcriptionCell cycle progressionCell proliferationImmune response modulation
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Disease associations

Cancer (due to high demand for nucleotides in rapidly dividing cells)Infection/antiviral therapy targetsAutoimmune disease/immunosuppression targetsGenetic disorders of metabolism (e.g., Lesch–Nyhan syndrome from HGPRT deficiency)
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Safety considerations

Myelosuppression/bone marrow suppression due to effects on rapidly dividing hematopoietic cells.Gastrointestinal toxicity.Immunosuppression leading to increased infection risk.Potential teratogenicity.
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Interacting drugs

Methotrexate

10 more in the full profile.

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Biomarkers

Expression levels of target enzymes such as thymidylate synthase and IMPDH in tumor tissue can predict response to inhibitors.IGFBP2 has been associated with copper metabolism and ribonucleotide reductase activity as a biomarker in glioma progression and immunotherapy response.

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