Purine and pyrimidine synthesis pathway

The purine and pyrimidine synthesis pathways comprise two fundamental metabolic routes that generate purine nucleotides (adenine, guanine) and pyrimidine nucleotides (cytosine, thymine, uracil), respectively. In the de novo pathway, purine synthesis constructs the purine ring directly onto phosphoribosyl pyrophosphate (PRPP) through a sequence of at least ten enzyme-catalyzed steps, ultimately forming inosine monophosphate (IMP), which serves as a branch point for adenosine and guanosine nucleotides. Pyrimidine synthesis forms the pyrimidine ring first (via carbamoyl phosphate synthase II, aspartate transcarbamylase, and dihydroorotase, collectively called CAD), which is then attached to PRPP to generate orotate monophosphate (OMP), subsequently converted to uridine monophosphate (UMP) and then to other pyrimidines. These pathways are essential for DNA and RNA synthesis, as well as for producing nucleotide-derived cofactors and cellular signaling molecules. They are upregulated in rapidly proliferating cells, such as cancer and immune cells, and are targeted by several classes of antimetabolite drugs in oncology and immunology. Dysfunctions in these pathways contribute to several inherited metabolic diseases and are subject to complex regulation to maintain nucleotide pool balance.

Other names

de novo purine biosynthesisde novo pyrimidine biosynthesisnucleotide biosynthesis pathways

Inhibition of nucleotide biosynthetic enzymes (e.g., DHFR, IMPDH, DHODH) to suppress cell proliferation, especially in cancer and autoimmune diseases