Cytidine deaminase
EC=3.5.4.5
Alternative name(s):
Cytidine aminohydrolase
Uridine phosphorylase
Short name=UPase
EC=2.4.2.3
- Function
- Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
- Catalytic activity
- Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate.
- Pathway
- Pyrimidine metabolism; UMP biosynthesis via salvage pathway; uracil from uridine (phosphorylase route): step 1/1.
- Subunit structure
- Homodimer.
- Induction
- By vitamin D3 and a mixture of inflammatory cytokines: TNF, IL1/interleukin-1 and IFNG/IFN-gamma.
Dihydropyrimidine dehydrogenase [NADP(+)]
Short name=DHPDHase
Short name=DPD
EC=1.3.1.2
Alternative name(s):
Dihydrothymine dehydrogenase
Dihydrouracil dehydrogenase
- Function
- Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
- Catalytic activity
- 5,6-dihydrouracil + NADP+ = uracil + NADPH.
- Cofactor
- Binds 2 FAD. / Binds 2 FMN. / Binds 4 4Fe-4S clusters. Contains approximately 16 iron atoms per subunit.
- Pathway
- Amino-acid biosynthesis; beta-alanine biosynthesis.
- Subunit structure
- Homodimer.
- Subcellular location
- Cytoplasm.
- Tissue specificity
- Found in most tissues with greatest activity found in liver and peripheral blood mononuclear cells.
- Involvement in disease
- Dihydropyrimidine dehydrogenase deficiency (DPYDD) [MIM:274270]: A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Dihydropyrimidinase
Short name=DHP
Short name=DHPase
EC=3.5.2.2
Alternative name(s):
Dihydropyrimidine amidohydrolase
Hydantoinase
- Function
- Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
- Catalytic activity
- 5,6-dihydrouracil + H2O = 3-ureidopropanoate.
- Cofactor
- Binds 2 zinc ions per subunit. Ref.4
- Subunit structure
- Homotetramer Probable.
- Tissue specificity
- Liver and kidney.
- Post-translational modification
- Carbamylation allows a single lysine to coordinate two zinc ions.
- Involvement in disease
- Dihydropyrimidinase deficiency (DHPD) [MIM:222748]: A disorder characterized by dihydropyrimidinuria and associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Beta-ureidopropionase
EC=3.5.1.6
Alternative name(s):
BUP-1
Beta-alanine synthase
N-carbamoyl-beta-alanine amidohydrolase
- Function
- Converts N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to, respectively, beta-aminoisobutyric acid and beta-alanine, ammonia and carbon dioxide.
- Catalytic activity
- N-carbamoyl-beta-alanine + H2O = beta-alanine + CO2 + NH3.
- Cofactor
- Binds 1 zinc ion per subunit Probable.
- Enzyme regulation
- Allosteric enzyme with positive cooperativity toward the substrate N-carbamoyl-beta-alanine By similarity.
- Pathway
- Amino-acid biosynthesis; beta-alanine biosynthesis.
- Subcellular location
- Cytoplasm.
- Involvement in disease
- Beta-ureidopropionase deficiency (BUPD) [MIM:613161]: An inborn error of metabolism due to a defect in pyrimidine degradation. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine.
Note: The disease is caused by mutations affecting the gene represented in this entry.
