Enzymes in de novo purine and pyrimidine synthesis

The enzymes involved in de novo purine and pyrimidine synthesis are a group of catalytic proteins responsible for the step-by-step assembly of nucleotide bases from simple precursor molecules like amino acids, carbon dioxide, and ribose-5-phosphate (Lehninger Principles of Biochemistry, 2017). These pathways are fundamental to cellular life, providing the essential building blocks (ATP, GTP, CTP, UTP, and TTP) required for DNA replication, RNA transcription, and energy metabolism. Because rapidly proliferating cells, such as malignant cells and activated immune cells, have a significantly higher demand for nucleotides than quiescent cells, these enzymes are major therapeutic targets in oncology and rheumatology (StatPearls, Methotrexate, 2023). Pharmacological intervention typically involves antimetabolites that mimic natural substrates or cofactors, thereby inhibiting key enzymes such as dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), or dihydroorotate dehydrogenase (DHODH) (StatPearls, Fluorouracil, 2023). For example, methotrexate inhibits DHFR to deplete folate pools, while 5-fluorouracil targets TYMS to block thymidine production (NCBI, Mycophenolate Mofetil, 2022). While highly effective at slowing disease progression, these drugs often carry significant safety concerns, including myelosuppression and gastrointestinal toxicity, due to their impact on other rapidly dividing healthy tissues (StatPearls, Leflunomide, 2023).

Other names

De novo nucleotide biosynthetic enzymesPurine and pyrimidine metabolic enzymesNucleotide synthesis pathway enzymesDe novo nucleotide synthesis pathway

Inhibition of specific catalytic steps in the de novo synthesis of purine or pyrimidine nucleotides, leading to the depletion of DNA and RNA precursors and subsequent inhibition of cell division.