Pyrimidinemetabolisme

Pyrimidinemetabolisme describes the biochemical pathways that cells use to synthesize and degrade the pyrimidine ring, a fundamental component of nucleic acids, RNA, and DNA. The synthesis of pyrimidines is a cooperative, multi‑enzyme process that begins in the cytosol with the production of carbamoyl phosphate by carbamoyl phosphate synthetase II and proceeds through a series of eight enzymatic steps to produce uridine monophosphate (UMP). Regulation of this pathway is heavily feedback‑controlled: the end products UTP, CTP, and dCTP inhibit the first enzyme, ensuring homeostasis of nucleotide pools.

Once formed, UMP is phosphorylated to UM and CMP, then to CDP and to CTP, which is the direct precursor for RNA synthesis and a substrate for DNA synthesis as dCTP after deamination. In eukaryotes, DNA synthesis additionally requires the reduction of ribonucleotide diphosphates to deoxyribonucleotides via ribonucleotide reductase, a step influenced by the redox state of the cell.

Degradation of pyrimidines occurs through the catabolic branch of the metabolic network. UMP and CTP can be deaminated to form xanthosine monophosphate (XMP) and then subsequently broken down to uracil, which is further degraded to β‐ureidopropionate and then to β‑aminoisobutyric acid. This catabolism eventually yields molecules for energy production or for excretion, depending on tissue type.

Defects in pyrimidine metabolism can lead to a range of disorders such as congenital dwarfism (due to mutations in the enzyme dihydroorotate dehydrogenase), the metabolic disease orotic aciduria, or predisposition to certain cancers. Therapies for these conditions often involve supplementation with missing nucleotides or inhibitors of de novo synthesis pathways and can be tailored to individual genetic mutations.