Despite a diet that may be rich in nucleoproteins, dietary purines and pyrimidines are not incorporated directly into tissue nucleic acids. Humans synthesize the nucleic acids and their derivatives ATP, NAD+, coenzyme A, etc, from amphibolic intermediates. However, injected purine or pyrimidine analogs, including potential anticancer drugs, may nevertheless be incorporated into DNA. The biosyntheses of purine and pyrimidine ribonucleotide triphosphates (NTPs) and dNTPs are precisely regulated events. Coordinated feedback mechanisms ensure their production in appropriate quantities and at times that match varying physiologic demand (eg, cell division). Human diseases that involve abnormalities in purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. Diseases of pyrimidine biosynthesis are rarer, but include orotic acidurias. Unlike the low solubility of uric acid formed by catabolism of purines, the end products of pyrimidine catabolism (carbon dioxide, ammonia, β-alanine, and γ-aminoisobutyrate) are highly water soluble. One genetic disorder of pyrimidine catabolism, β-hydroxybutyric aciduria, is due to total or partial deficiency of the enzyme dihydropyrimidine dehydrogenase. This disorder of pyrimidine catabolism, also known as combined uraciluria-thyminuria, is also a disorder of β-amino acid biosynthesis, since the formation of β-alanine and of β-aminoisobutyrate is impaired. A nongenetic form can be triggered by administration of 5-fluorouracil to patients with low levels of dihydropyrimidine dehydrogenase.