Pyrimidine Metabolism

Key points

• • The pyrimidine bases are cytosine, thymine (in DNA) and uracil (in RNA), and they are built up on a ready-made ring rather than on a sugar as purines are.
• • In pyrimidine synthesis the ring is made first (by way of orotic acid) and only then attached to the sugar-phosphate, the opposite order to purine synthesis.
• • The pathway starts from carbamoyl phosphate made in the cytosol, unlike the urea cycle, whose carbamoyl phosphate is made in the mitochondria.
• • Unlike purines, which break down to insoluble uric acid, pyrimidines break down to soluble products such as beta-alanine or beta-aminoisobutyrate, so they do not cause gout.
• • Orotic aciduria is an inherited block in the pathway that lets orotic acid build up, giving a megaloblastic anaemia that does not respond to vitamin B12 or folate.
• • Because the pathway feeds DNA synthesis, several anticancer and antiviral drugs act by blocking pyrimidine production.