6,7-dihydropteridine reductase
| 6,7-dihydropteridine reductase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Dihydropteridine reductase dimer, Human | |||||||||
| Identifiers | |||||||||
| EC no. | 1.5.1.34 | ||||||||
| CAS no. | 9074-11-7 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
6,7-dihydropteridine reductase (EC 1.5.1.34, also dihydrobiopterin reductase) is an enzyme that catalyzes the chemical reaction
The substrates of this enzyme are dihydrobiopterin (specifically the isomer (6R)-L-erythro-6,7-dihydrobiopterin), reduced nicotinamide adenine dinucleotide (NADH), and two protons. Its products are tetrahydropteridine and oxidised NAD+. Nicotinamide adenine dinucleotide phosphate can be used as an alternative cofactor.[1][2][3] The enzyme participates in folate biosynthesis. In the human genome, the enzyme is encoded by the QDPR gene.
Nomenclature
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 5,6,7,8-tetrahydropteridine:NAD(P)+ oxidoreductase. Other names in common use include 6,7-dihydropteridine:NAD(P)H oxidoreductase, DHPR, NAD(P)H:6,7-dihydropteridine oxidoreductase, NADH-dihydropteridine reductase, NADPH-dihydropteridine reductase, NADPH-specific dihydropteridine reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide), reductase, dihydropteridine reductase, dihydropteridine reductase (NADH), and 5,6,7,8-tetrahydropteridine:NAD(P)H+ oxidoreductase.
The enzyme is believed to act on the so-called "quinonoid" form of the starting dihydrobiopterin.[2][4][5] This is in contrast to the enzyme dihydrofolate reductase, which normally acts on dihydrofolic acid but can also reduce the isomer, L-erythro-7,8-dihydrobiopterin.[6]
Clinical significance
Dihydropteridine reductase deficiency is a defect in the regeneration of tetrahydrobiopterin. Many patients have significant developmental delays despite therapy, develop brain abnormalities, and are prone to sudden death. The reason is not completely clear, but might be related to the accumulation of dihydrobiopterin and abnormal metabolism of folic acid.[7] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).[8] Dihydropteridine reductase deficiency is treated with tyrosine supplements, a controlled diet which is lacking in phenylalanine,[9] well as supplementation of L-DOPA.
See also
References
- ^ Hasegawa H (January 1977). "Dihydropteridine reductase from bovine liver. Purification, crystallization, and isolation of a binary complex with NADH". Journal of Biochemistry. 81 (1): 169–77. doi:10.1093/oxfordjournals.jbchem.a131432. PMID 191436.
- ^ a b Lind KE (February 1972). "Dihydropteridine reductase. Investigation of the specificity for quinoid dihydropteridine and the inhibition by 2,4-diaminopteridines". European Journal of Biochemistry. 25 (3): 560–2. doi:10.1111/j.1432-1033.1972.tb01728.x. PMID 4402916.
- ^ Nakanishi N, Hasegawa H, Watabe S (March 1977). "A new enzyme, NADPH-dihydropteridine reductase in bovine liver". Journal of Biochemistry. 81 (3): 681–5. doi:10.1093/oxfordjournals.jbchem.a131504. PMID 16875.
- ^ Enzyme 1.5.1.4 at KEGG Pathway Database.
- ^ Kono, Haruka; Hara, Satoshi; Furuta, Tadaomi; Ichinose, Hiroshi (2023). "Binding profile of quinonoid -dihydrobiopterin to quinonoid -dihydropteridine reductase examined by in silico and in vitro analyses". The Journal of Biochemistry. 174 (5): 441–450. doi:10.1093/jb/mvad062. PMID 37540845.
- ^ Enzyme 1.5.1.3 at KEGG Pathway Database.
- ^ Longo N (June 2009). "Disorders of biopterin metabolism". Journal of Inherited Metabolic Disease. 32 (3): 333–42. doi:10.1007/s10545-009-1067-2. PMID 19234759. S2CID 13117236.
- ^ "Patient registry".
- ^ Pawlina, Wojciech; Ross, Michael W. (2006). Histology: a text and atlas: with correlated cell and molecular biology. Philadelphia: Lippincott Williams & Wilkins. ISBN 0-7817-5056-3.