Nucleosides are composed of a heterocyclic ring (defined as the base) that is attached to a ribose. Addition to a nucleoside of a phosphate, at carbon 5 of the ribose, produces a nucleotide. Nucleotides function as ubiquitous building blocks for the synthesis of all nucleic acids, and also function in enzymatic reactions as cofactors and as a source of energy. These central metabolic roles require their continued biosynthesis from readily available precursors, and this process is defined as de novo nucleotide synthesis. The synthesis of purines starts with ribose-phosphate, to which are attached in a stepwise fashion the individual atoms of the heterocyclic base. Pyrimidine synthesis starts with the stepwise formation of the base, to which is then added the ribose-phosphate. Bases and nucleosides may also be recycled in salvage pathways.

Key concepts:

• Nucleotides are so essential to metabolism that genetic defects generally are lethal, and for humans only a few gene defects are observed, at a low frequency.
  
• Many of the enzymatic reactions in the de novo biosynthesis of nucleotides are combined as two or more reactions catalysed by a single multidomain protein. This has made nucleotide biosynthesis more efficient.
  
• For a few of the biosynthetic steps alternate enzymatic strategies have emerged between bacteria and vertebrates, and these present possible targets for drugs as selective antibiotics.