Pathways in Nucleotide Metabolism

Most organisms can synthesize purine and pyrimidine nucleotides (Figure 4.2) from low-molecular-weight precursors in amounts sufficient for their needs. These de novo pathways (Figure 22.1) are essentially identical in all organisms. Nucleotides can also be synthesized from the partial breakdown of previously synthesized nucleotides. These pathways are called salvage pathways. A schematic showing the simple relationships between de novo and salvage pathways is shown in Figure 22.2.

Degradation of pyrimidine and purine bases can occur intracellularly as a result of cell death or, in animals, through digestion of nucleic acids ingested in the diet (major source). Cleavage begins at the phosphodiester bonds (Figure 4.1) with endonucleases (pancreatic ribonuclease or DNase) in the small intestine. The oligonucleotides resulting from this action are then cleaved exonucleolytically by nonspecific enzymes called phosphodiesterases. The products of this reaction are 5' or 3' monophosphates, depending on the specificities of the enzymes. Phosphomonoesterases called nucleotidases cleave phosphates from the nucleotides, yielding nucleosides and orthophosphate. Nucleoside phosphorylases act, as shown here to yield a base and ribose-1-phosphate. If bases or nucleosides are not reused for nucleic acid synthesis via salvage pathways, the bases are further degraded to uric acid (purines) or -ureidopropionate (pyrimidines).

Note that the reaction (shown here) is reversible, providing a way for a cell to rebuild a nucleoside from ribose-1-phosphate and a base. Some cells have enzymes called nucleoside kinases which, in the presence of ATP, convert the nucleoside to a nucleotide.

See also: The Importance of PRPP, De Novo Biosynthesis of Purine Nucleotides, Excessive Uric Acid in Purine Degradation, De Novo Pyrimidine Nucleotide Metabolism, Nucleotide Salvage Synthesis, Deoxyribonucleotide Biosynthesis, Biosynthesis of Thymine Deoxyribonucleotides, Salvage Routes to Deoxyribonucleotide Synthesis

INTERNET LINKS:

> 1. Purine Metabolism

> 2. Pyrimidine Metabolism

> 3. Purine and Pyrimidine Metabolism