Nucleotide metabolism

This overview addresses nucleotide metabolism, with particular emphasis on how nucleotides are synthesised, salvaged, and degraded, the enzymes and regulatory mechanisms involved, and the clinical impact of metabolic disruptions. Cells acquire nucleotides through de novo synthesis, which builds nucleotides from simpler molecules, and salvage pathways, which recycle bases and nucleosides from nucleic acid breakdown. Purine and pyrimidine nucleotides use different synthetis routes. De novo synthesis is energy intensive and mainly active in rapidly dividing cells, while salvage conserves energy, especially in non-dividing tissues. The balance between these pathways ensures an adequate supply of nucleotides and prevents toxic accumulations or deficiencies. De novo purine synthesis starts with ribose-five-phosphate from the pentose phosphate pathway, activated to five-phosphoribosyl-one-pyrophosphate (PRPP). Sequential addition of atoms from amino acids such as glutamine, glycine, aspartate, and cofactors including tetrahydrofolate yields inosine monophosphate (IMP), which serves as a precursor for AMP and GMP. In contrast, pyrimidine synthesis involves the formation of the pyrimidine ring from carbamoyl phosphate and aspartate to create orotate. Orotate then attaches to PRPP and is converted to uridine monophosphate (UMP), which acts as the precursor for