Sepiapterin reductase

Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene.{{cite journal |vauthors=Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T | title = Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis | journal = Biochem Biophys Res Commun | volume = 179 | issue = 1 | pages = 183–189 |date=Oct 1991 | pmid = 1883349 | doi =10.1016/0006-291X(91)91352-D }}{{cite journal |vauthors=Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U | title = The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative | journal = Chem Biol Interact | volume = 178 | issue = 1–3 | pages = 94–98 |date=Feb 2009 | pmid = 19027726 | pmc = 2896744| doi = 10.1016/j.cbi.2008.10.040 | bibcode = 2009CBI...178...94P }}{{cite web | title = Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6697}}

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.

Reaction

{{infobox enzyme

| align = left

| Name = sepiapterin reductase

| EC_number = 1.1.1.153

| CAS_number =

| GO_code = 0004757

| image = 4hwk.jpg

| width = 270

| caption = Sepiapterin reductase homodimer, Human

}}

Sepiapterin reductase (SPR) catalyzes the chemical reaction

L-erythro-7,8-dihydrobiopterin + NADP+ $\rightleftharpoons$ 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.

{{Cite web|url=http://brenda-enzymes.info/enzyme.php?ecno=1.1.1.153|title = BRENDA - Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)}}

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.{{Cite journal|vauthors=Pearl PL, Taylor JL, Trzcinski S, Sokohl A | title = The pediatric neurotransmitter disorders| journal = J Child Neurol| volume = 22| issue = 5| pages = 606–616|date=May 2007| pmid = 17690069| doi=10.1177/0883073807302619| s2cid = 10689202}} 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).{{cite web|title=Patient registry|url=http://intd-online.org/}}

References

{{cite journal | author = Katoh S | date = 1971 | title = Sepiapterin Reductase from Horse Liver: Purification and Properties of the Enzyme. | journal = Arch. Biochem. Biophys. | volume = 146 | pages = 202–214 | doi = 10.1016/S0003-9861(71)80057-7 | pmid = 4401291 | issue = 1 }}
{{cite journal |vauthors=Matsubara M, Katoh S, Akino M, Kaufman S | date = 1966 | title = Sepiapterin Reductase. | journal = Biochim. Biophys. Acta | volume = 122 | pages = 202–212 | pmid = 5969298 | issue = 2 | doi=10.1016/0926-6593(66)90062-2}}
{{cite journal | author=Takikawa S |title=Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver |journal=Eur. J. Biochem. |volume=161 |issue= 2 |pages= 295–302 |year= 1987 |pmid= 3536512 |doi=10.1111/j.1432-1033.1986.tb10446.x | author2=Curtius HC | author3=Redweik U | last4=Leimbacher | first4=Walter | last5=Ghisla | first5=Sandro |url=http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-56746 |doi-access=free }}
{{cite journal |vauthors=Thöny B, Heizmann CW, Mattei MG |title=Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization |journal=Genomics |volume=26 |issue= 1 |pages= 168–170 |year= 1995 |pmid= 7782081 |doi=10.1016/0888-7543(95)80101-Q }}
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{{cite book | author=Maier J |volume=338 |pages= 195–8 |pmid= 8304109 |doi= 10.1007/978-1-4615-2960-6_39| author2=Schott K | author3=Werner T | last4=Bacher | first4=A | last5=Ziegler | first5=I |title=Chemistry and Biology of Pteridines and Folates |chapter=Northern Blot Analysis of Sepiapterin Reductase mRNA in Mammalian Cell Lines and Tissues |series=Advances in Experimental Medicine and Biology |date=1993 |isbn=978-1-4613-6287-6 }}
{{cite journal | author=Maier J |title=Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species |journal=Exp. Cell Res. |volume=204 |issue= 2 |pages= 217–222 |year= 1993 |pmid= 8440319 |doi= 10.1006/excr.1993.1027 | author2=Schott K | author3=Werner T | last4=Bacher | first4=A | last5=Ziegler | first5=I }}
{{cite journal | author=Suzuki Y |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–156 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 | author2=Yoshitomo-Nakagawa K | author3=Maruyama K | last4=Suyama | first4=A | last5=Sugano | first5=S }}
{{cite journal | author=Blau N |title=Dihydropteridine reductase deficiency localized to the central nervous system |journal=J. Inherit. Metab. Dis. |volume=21 |issue= 4 |pages= 433–434 |year= 1998 |pmid= 9700606 |doi=10.1023/A:1005327313348 | author2=Thöny B | author3=Renneberg A | last4=Arnold | first4=L. A. | last5=Hyland | first5=K. |s2cid=20969872 }}
{{cite journal | author=Ohye T |title=Genomic organization and chromosomal localization of the human sepiapterin reductase gene |journal=Biochem. Biophys. Res. Commun. |volume=251 |issue= 2 |pages= 597–602 |year= 1998 |pmid= 9792819 |doi= 10.1006/bbrc.1998.9503 | author2=Hori TA | author3=Katoh S | last4=Nagatsu | first4=T | last5=Ichinose | first5=H }}
{{cite journal | author=Blau N |title=Variant of dihydropteridine reductase deficiency without hyperphenylalaninaemia: effect of oral phenylalanine loading |journal=J. Inherit. Metab. Dis. |volume=22 |issue= 3 |pages= 216–220 |year= 1999 |pmid= 10384371 |doi=10.1023/A:1005584627797 | author2=Thöny B | author3=Renneberg A | last4=Penzien | first4=J. M. | last5=Hyland | first5=K. | last6=Hoffmann | first6=G. F. |s2cid=30670124 }}
{{cite journal | author=Bonafé L |title=Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia |journal=Am. J. Hum. Genet. |volume=69 |issue= 2 |pages= 269–277 |year= 2001 |pmid= 11443547 |doi=10.1086/321970 | pmc=1235302 | author2=Thöny B | author3=Penzien JM | last4=Czarnecki | first4=Barbara | last5=Blau | first5=Nenad }}
{{cite journal |vauthors=Fujimoto K, Takahashi SY, Katoh S |title=Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca²⁺/calmodulin-dependent protein kinase II |journal=Biochim. Biophys. Acta |volume=1594 |issue= 1 |pages= 191–8 |year= 2002 |pmid= 11825621 |doi=10.1016/S0167-4838(01)00300-4 }}
{{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–16903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 | author2=Feingold EA | author3=Grouse LH | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD |bibcode=2002PNAS...9916899M |doi-access=free }}
{{cite journal | author=Franscini N |title=Functional tetrahydrobiopterin synthesis in human platelets |journal=Circulation |volume=110 |issue= 2 |pages= 186–192 |year= 2005 |pmid= 15197144 |doi= 10.1161/01.CIR.0000134281.82972.57 | author2=Bachli EB | author3=Blau N | last4=Fischler | first4=M | last5=Walter | first5=RB | last6=Schaffner | first6=A | last7=Schoedon | first7=G | doi-access=free }}
{{cite journal | author=Steinberger D |title=Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene (SPR) in a patient with dopa-responsive dystonia |journal=Neurogenetics |volume=5 |issue= 3 |pages= 187–190 |year= 2005 |pmid= 15241655 |doi= 10.1007/s10048-004-0182-3 | author2=Blau N | author3=Goriuonov D | last4=Bitsch | first4=Juliane | last5=Zuker | first5=Michael | last6=Hummel | first6=Sibylla | last7=Müller | first7=Ulrich |s2cid=4833737 }}
{{cite journal | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–2127 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 | author2=Wagner L | author3=Feingold EA | last4=Shenmen | first4=CM | last5=Grouse | first5=LH | last6=Schuler | first6=G | last7=Klein | first7=SL | last8=Old | first8=S | last9=Rasooly | first9=R }}
{{cite journal | author=Sharma M |title=The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations |journal=J. Med. Genet. |volume=43 |issue= 7 |pages= 557–562 |year= 2006 |pmid= 16443856 |doi= 10.1136/jmg.2005.039149 | pmc=2593029 | author2=Mueller JC | author3=Zimprich A | last4=Lichtner | first4=P | last5=Hofer | first5=A | last6=Leitner | first6=P | last7=Maass | first7=S | last8=Berg | first8=D | last9=Dürr | first9=A }}
{{cite journal | author=Farrugia R |title=Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population |journal=Mol. Genet. Metab. |volume=90 |issue= 3 |pages= 277–283 |year= 2007 |pmid= 17188538 |doi= 10.1016/j.ymgme.2006.10.013 | author2=Scerri CA | author3=Montalto SA | last4=Parascandolo | first4=Raymond | last5=Neville | first5=Brian G.R. | last6=Felice | first6=Alex E. }}
{{cite journal | author=Tobin JE |title=Sepiapterin reductase expression is increased in Parkinson's disease brain tissue |journal=Brain Res. |volume=1139 |pages= 42–47 |year= 2007 |pmid= 17270157 |doi= 10.1016/j.brainres.2007.01.001 | pmc=1868471 | author2=Cui J | author3=Wilk JB | last4=Latourelle | first4=J | last5=Laramie | first5=J | last6=McKee | first6=A | last7=Guttman | first7=M | last8=Karamohamed | first8=S | last9=Destefano | first9=A }}

External links

{{PDBe-KB2|P35270|Human Sepiapterin reductase}}
{{PDBe-KB2|Q64105|Mouse Sepiapterin reductase}}

Category:EC 1.1.1

Category:NADPH-dependent enzymes

Category:Enzymes of known structure