Nucleotide biosynthesis is the enzymatic production of nucleotides from metabolic precursors. De novo pathways combine sources of carbon and nitrogen with activated ribose, consuming energy to construct the purine or pyrimidine nucleotide framework [1]. Pyrimidine synthesis forms the ring through successive reactions before generating uridine monophosphate, which supplies further pyrimidine nucleotide conversions [2]. In bacteria, the resulting nucleotide pools support nucleic-acid synthesis, energy transfer, and signaling, linking biosynthetic activity to broader cellular metabolism [3]. Regulation of phosphoribosyl pyrophosphate synthesis links activated ribose supply with nucleotide production and cellular biosynthetic demand [4]. Subsequent phosphorylation produces higher phosphate forms, and ribonucleotide reduction supplies deoxyribonucleotide precursors. Salvage reactions incorporating preformed bases or nucleosides also contribute to the pools that are maintained alongside de novo synthesis [5].
- nucleotides
- de novo synthesis
- phosphoribosyl pyrophosphate
- nucleotide salvage
Cancer and biochemical research·Molecular Biology·Biochemistry, Genetics and Molecular Biology·Life Sciences
References
- Andrew N Lane; Teresa W-M Fan; Regulation of Mammalian Nucleotide Metabolism and Biosynthesis. Nucleic Acids Res. 2015, 43, 2466-2485. [CrossRef]
- Nicholas J. Mullen; Pankaj K. Singh; Nucleotide Metabolism: A Pan-cancer Metabolic Dependency. Nat. Rev. Cancer 2023, 23, 275-294. [CrossRef]
- Mariya I. Goncheva; Denny Chin; David E. Heinrichs; Nucleotide Biosynthesis: the Base of Bacterial Pathogenesis. Trends Microbiol. 2022, 30, 793-804. [CrossRef]
- John T. Cunningham; Melissa V. Moreno; Alessia Lodi; Sabrina M. Ronen; Davide Ruggero; Protein and Nucleotide Biosynthesis Are Coupled by a Single Rate-Limiting Enzyme, PRPS2, to Drive Cancer. Cell 2014, 157, 1088-1103. [CrossRef]
- Riya Joshi; Alastair G. McEwan; Ulrike Kappler; De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence. Microbiologyopen 2026, 15, e70358. [CrossRef]