Purine

Purine is a heterocyclic aromatic compound consisting of a pyrimidine ring fused to an imidazole ring, giving a two-ring system with the formula C5H4N4. In biology, the major purine bases are adenine and guanine, which form the purine components of nucleic acids. Purines serve as essential building blocks of DNA and RNA and as components of many cellular cofactors and signaling molecules.

Purine nucleotides play multiple roles in the cell. They are the nucleotides that encode genetic information in DNA and RNA, and in their phosphorylated forms they act as energy carriers (ATP and GTP) and as components of signaling molecules and cofactors. Purine-containing cofactors include NAD+, FAD, and derivatives of adenosine. Purine metabolism ends with the production of uric acid in humans, which is excreted in urine.

Biosynthesis and salvage occur through two main routes. De novo purine synthesis builds the purine ring on ribose-5-phosphate (PRPP) using substrates such as glutamine, glycine, formate, CO2, and aspartate, eventually yielding inosine monophosphate (IMP), which is then converted to AMP or GMP. Purine salvage pathways recycle free bases (adenine, guanine, hypoxanthine) by attaching them to PRPP to reform nucleotides via enzymes such as HGPRT and APRT.

Regulation of purine metabolism involves feedback inhibition by IMP, AMP, and GMP, along with control by cellular energy and folate cofactor availability. Clinically, disorders include Lesch-Nyhan syndrome from HGPRT deficiency; gout arising from excess uric acid; and severe combined immunodeficiency due to adenosine deaminase deficiency. Purine metabolism is also targeted in cancer and autoimmune therapies with purine analogs like 6-mercaptopurine and azathioprine.