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Notes

• Subtopic: Importance of Phosphoribosyl Pyrophosphate (PRPP) Phosphoribosyl pyrophosphate (PRPP) is essential in nucleotide biosynthesis. In these pathways, the ribose structure remains in the final nucleotide, unlike in tryptophan and histidine biosynthesis. An amino acid acts as a key precursor: glycine for purines and aspartate for pyrimidines. Glutamine provides most amino groups, participating in five steps of de novo pathways. Aspartate also supplies amino groups in two steps of purine synthesis. • Subtopic: Features of Nucleotide Biosynthesis Two notable features are worth mentioning. First, especially in the de novo purine pathway, enzymes often form large, multienzyme complexes within the cell—a recurring theme in metabolism. Second, cellular pools of nucleotides (except ATP) are very small, likely 1% or less of the amounts needed for DNA synthesis. Consequently, cells must continuously synthesize nucleotides during nucleic acid production, and nucleotide synthesis can limit DNA replication and transcription rates. Due to their critical role in dividing cells, inhibitors of nucleotide synthesis are significant in modern medicine. • Subtopic: Overview of Purine and Pyr...