Enzymes involved in de novo nucleic acid synthesis

Enzymes involved in de novo nucleic acid synthesis represent a diverse group of catalytic proteins responsible for the step-by-step assembly of purine and pyrimidine nucleotides from simple metabolic precursors like amino acids, carbon dioxide, and ribose-5-phosphate (NCBI Bookshelf: Biochemistry, Section 25.2). These pathways are essential for providing the deoxyribonucleotide and ribonucleotide triphosphates required for DNA replication and RNA transcription, respectively. Because high rates of nucleotide synthesis are a hallmark of rapidly dividing cells, these enzymes are critical therapeutic targets in the treatment of cancer and autoimmune disorders (StatPearls: Antimetabolites). Antimetabolite drugs, such as methotrexate and 5-fluorouracil, function by inhibiting specific enzymes within these pathways, thereby depleting the cellular pool of nucleotides and inducing cell cycle arrest or apoptosis (PubMed: PMID 25435214). Furthermore, the de novo pathways are often distinct in certain pathogens compared to humans, allowing for the development of selective antimicrobial and antiparasitic agents. However, because these pathways are also active in healthy proliferating tissues like the bone marrow and intestinal epithelium, drugs targeting these enzymes often carry significant toxicities such as myelosuppression and mucositis (StatPearls: Methotrexate).

Other names

De novo nucleotide biosynthesis enzymesPurine and pyrimidine synthesis enzymesNucleotide metabolic enzymes

Inhibition of key rate-limiting enzymes in the purine and pyrimidine biosynthetic pathways, leading to the depletion of intracellular nucleotide pools, which subsequently inhibits DNA and RNA synthesis and triggers cell cycle arrest or apoptosis (StatPearls: Antimetabolites).