Sepiapterin reductase

Last updated

SPR
Protein SPR PDB 1z6z.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SPR , SDR38C1, sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase), sepiapterin reductase
External IDs OMIM: 182125; MGI: 103078; HomoloGene: 37735; GeneCards: SPR; OMA:SPR - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003124

NM_011467

RefSeq (protein)

NP_003115

n/a

Location (UCSC) Chr 2: 72.89 – 72.89 Mb Chr 6: 85.11 – 85.11 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene. [5] [6] [7]

Contents

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases. SPR plays an important role in the biosynthesis of tetrahydrobiopterin. [7]

Reaction

sepiapterin reductase
4hwk.jpg
Sepiapterin reductase homodimer, Human
Identifiers
EC no. 1.1.1.153
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
Search
PMC articles
PubMed articles
NCBI proteins

Sepiapterin reductase (SPR) catalyzes the chemical reaction

L-erythro-7,8-dihydrobiopterin + NADP+ sepiapterin + NADPH + H+

Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP+, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H+).

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP+ oxidoreductase. This enzyme participates in folate biosynthesis.

[8]

Clinical significance

Mutations of the SPR gene may cause sepiapterin reductase deficiency, a rare disease. The clinical phenotype can include progressive psychomotor retardation, altered tone, seizures, choreoathetosis, temperature instability, hypersalivation, microcephaly, and irritability. Patients with sepiapterin reductase deficiency also manifest dystonia with diurnal variation, oculogyric crises, tremor, hypersomnolence, oculomotor apraxia, and weakness. [9] 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). [10]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116096 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033735 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (Oct 1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochem Biophys Res Commun. 179 (1): 183–189. Bibcode:1991BBRC..179..183I. doi:10.1016/0006-291X(91)91352-D. PMID   1883349.
  6. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact. 178 (1–3): 94–98. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC   2896744 . PMID   19027726.
  7. 1 2 "Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)".
  8. "BRENDA - Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)".
  9. Pearl PL, Taylor JL, Trzcinski S, Sokohl A (May 2007). "The pediatric neurotransmitter disorders". J Child Neurol . 22 (5): 606–616. doi:10.1177/0883073807302619. PMID   17690069. S2CID   10689202.
  10. "Patient registry".

Further reading