Biosynthesis of nucleic acids

Most microorganisms are able to synthesise the purines and pyrimidines that comprise the nitrogenous bases of DNA and RNA. These compounds are synthesised from a number of sources in reactions that require an input of ATP. The contribution of different compounds towards the purine skeleton of guanine or adenine is shown in Figure 6.36.

Figure 6.36 Purine structure. Several precursors contribute towards the formation of the purine base skeleton. The nitrogen atoms are donated by the amino acids glutamine, aspartate and glycine. Note the important role played by folic acid. The antimicrobial agent sulphonamide (Chapter 15) exerts its effect by inhibiting folic acid synthesis, which in turn affects synthesis of purine nucleotides

Figure 6.36 Purine structure. Several precursors contribute towards the formation of the purine base skeleton. The nitrogen atoms are donated by the amino acids glutamine, aspartate and glycine. Note the important role played by folic acid. The antimicrobial agent sulphonamide (Chapter 15) exerts its effect by inhibiting folic acid synthesis, which in turn affects synthesis of purine nucleotides

The purines are not synthesised as free bases but are associated with ribose-5-phosphate as complete nucleotides from the outset. Inosinic acid, which is formed initially, acts as a precursor for the other purine nucleotides.

Pyrimidines have a similarly complex synthesis. The amino acids aspartate and glu-tamine are involved in the synthesis of the precursor orotic acid. Note that unlike the purines, the skeleton of pyrimidines is fully formed before association with the ribose-5-phosphate moiety, which is itself derived from glucose (see biosynthesis of carbohydrates, above).

Ribonucleotides (as contained in RNA) are converted to deoxyribonucleotides (as contained in DNA) by a reduction reaction that may involve vitamin B12 acting as a cofactor.

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