Sepiapterin reductase
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| Location (UCSC) | Chr 2: 72.89 – 72.89 Mb | Chr 6: 85.11 – 85.11 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene.[5][6][7]
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 | |||||||||
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ExPASy NiceZyme view | | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Sepiapterin reductase (SPR) catalyzes the chemical reaction
L-erythro-7,8-dihydrobiopterin + NADP+ sepiapterin + NADPH + H+
Thus, the two
(H+).This enzyme belongs to the
folate biosynthesis
.
Clinical significance
Mutations of the SPR gene may cause
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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116096 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033735 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1883349.
- PMID 19027726.
- ^ a b "Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)".
- ^ "BRENDA - Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)".
- S2CID 10689202.
- ^ "Patient registry".
Further reading
- Katoh S (1971). "Sepiapterin Reductase from Horse Liver: Purification and Properties of the Enzyme". Arch. Biochem. Biophys. 146 (1): 202–214. PMID 4401291.
- Matsubara M, Katoh S, Akino M, Kaufman S (1966). "Sepiapterin Reductase". Biochim. Biophys. Acta. 122 (2): 202–212. PMID 5969298.
- Takikawa S, Curtius HC, Redweik U, Leimbacher W, Ghisla S (1987). "Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver". Eur. J. Biochem. 161 (2): 295–302. PMID 3536512.
- Thöny B, Heizmann CW, Mattei MG (1995). "Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization". Genomics. 26 (1): 168–170. PMID 7782081.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. PMID 8125298.
- Maier J, Schott K, Werner T, Bacher A, Ziegler I (1993). "Northern Blot Analysis of Sepiapterin Reductase mRNA in Mammalian Cell Lines and Tissues". Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology. Vol. 338. pp. 195–8. PMID 8304109.
- Maier J, Schott K, Werner T, Bacher A, Ziegler I (1993). "Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species". Exp. Cell Res. 204 (2): 217–222. PMID 8440319.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. PMID 9373149.
- Blau N, Thöny B, Renneberg A, Arnold LA, Hyland K (1998). "Dihydropteridine reductase deficiency localized to the central nervous system". J. Inherit. Metab. Dis. 21 (4): 433–434. S2CID 20969872.
- Ohye T, Hori TA, Katoh S, Nagatsu T, Ichinose H (1998). "Genomic organization and chromosomal localization of the human sepiapterin reductase gene". Biochem. Biophys. Res. Commun. 251 (2): 597–602. PMID 9792819.
- Blau N, Thöny B, Renneberg A, Penzien JM, Hyland K, Hoffmann GF (1999). "Variant of dihydropteridine reductase deficiency without hyperphenylalaninaemia: effect of oral phenylalanine loading". J. Inherit. Metab. Dis. 22 (3): 216–220. S2CID 30670124.
- Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N (2001). "Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia". Am. J. Hum. Genet. 69 (2): 269–277. PMID 11443547.
- Fujimoto K, Takahashi SY, Katoh S (2002). "Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II". Biochim. Biophys. Acta. 1594 (1): 191–8. PMID 11825621.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. PMID 12477932.
- Franscini N, Bachli EB, Blau N, Fischler M, Walter RB, Schaffner A, et al. (2005). "Functional tetrahydrobiopterin synthesis in human platelets". Circulation. 110 (2): 186–192. PMID 15197144.
- Steinberger D, Blau N, Goriuonov D, Bitsch J, Zuker M, Hummel S, et al. (2005). "Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene (SPR) in a patient with dopa-responsive dystonia". Neurogenetics. 5 (3): 187–190. S2CID 4833737.
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. PMID 15489334.
- Sharma M, Mueller JC, Zimprich A, Lichtner P, Hofer A, Leitner P, et al. (2006). "The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations". J. Med. Genet. 43 (7): 557–562. PMID 16443856.
- Farrugia R, Scerri CA, Montalto SA, Parascandolo R, Neville BG, Felice AE (2007). "Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population". Mol. Genet. Metab. 90 (3): 277–283. PMID 17188538.
- Tobin JE, Cui J, Wilk JB, Latourelle J, Laramie J, McKee A, et al. (2007). "Sepiapterin reductase expression is increased in Parkinson's disease brain tissue". Brain Res. 1139: 42–47. PMID 17270157.
External links
- Overview of all the structural information available in the PDB for UniProt: P35270 (Human Sepiapterin reductase) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: Q64105 (Mouse Sepiapterin reductase) at the PDBe-KB.
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