DRD4

DPYS

The DPYS gene encodes the enzyme dihydropyrimidinase, which is involved in the catabolism of pyrimidine bases, specifically uracil and thymine. This enzyme plays a crucial role in the pyrimidine degradation pathway, which is essential for nucleotide metabolism and the maintenance of cellular nucleotide pools.

Function

Dihydropyrimidinase, the protein product of the DPYS gene, catalyzes the second step in the degradation of pyrimidines. It converts 5,6-dihydrouracil to N-carbamoyl-β-alanine and 5,6-dihydrothymine to N-carbamoyl-β-aminoisobutyric acid. These reactions are part of the broader pyrimidine catabolic pathway, which ultimately leads to the production of β-alanine, a precursor for the synthesis of coenzyme A, and β-aminoisobutyric acid, which is excreted in urine.

Clinical Significance

Mutations in the DPYS gene can lead to a rare metabolic disorder known as dihydropyrimidinase deficiency. This condition is characterized by the accumulation of dihydropyrimidines in the body, which can result in neurological symptoms, developmental delay, and other clinical manifestations. The disorder is inherited in an autosomal recessive manner.

Dihydropyrimidinase deficiency can also affect the metabolism of certain chemotherapeutic drugs, such as 5-fluorouracil (5-FU), which are pyrimidine analogs. Patients with this deficiency may experience severe toxicity when treated with these drugs, necessitating careful monitoring and dose adjustment.

Genetic Information

The DPYS gene is located on chromosome 8q22.3. It consists of multiple exons and encodes a protein that is approximately 519 amino acids in length. The gene is expressed in various tissues, with high levels in the liver and kidney, which are key sites for pyrimidine metabolism.

Research and Developments

Ongoing research is focused on understanding the full spectrum of mutations in the DPYS gene and their phenotypic consequences. Studies are also exploring the role of dihydropyrimidinase in cancer biology, given its involvement in the metabolism of chemotherapeutic agents.

Also see

• Pyrimidine metabolism
• Dihydropyrimidinase deficiency
• 5-Fluorouracil
• Nucleotide metabolism