In humans, dietary nucleotide bases are rarely incorporated into nucleotides. As a result, humans must synthesize their own nucleotide bases (With the exception of a few parasitic prokaryotes, all organisms can synthesize nucleotides) and, although most tissues can produce at least small amounts, this tightly regulated synthesis occurs mainly in the liver.

Purine production occurs primarily in the liver, Purine biosynthesis begins with ribose-5-phosphate (R5P, a product of the ppp), and ends with the hypoxanthine containing inosine monophosphate.

In contrast to purines that are synthesized by building the ring system on the ribose, the pyrimidine ring is constructed first, then followed by attachment of the pyrimidine base to ribose. In both purine and pyrimidine synthesis, PRPP is used as the ribose donor, but that occurs at a different stage of the pathway.