Sepiapterin reductase
| Sepiapterin reductase | ||
|---|---|---|
|
||
| Ribbon model of the human SPR dimer according to 1Z6Z | ||
| Properties of human protein | ||
| Mass / length primary structure | 261 amino acids | |
| Secondary to quaternary structure | Homodimer | |
| Identifier | ||
| Gene name | SPR | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 1.1.1.153 , oxidoreductase | |
| Response type | Redox reaction | |
| Substrate | Sepiapterin + NADPH + H + | |
| Products | 7,8-dihydrobiopterin + NADP + | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 6697 | 20751 |
| Ensemble | ENSG00000116096 | ENSMUSG00000033735 |
| UniProt | P35270 | Q91XH5 |
| Refseq (mRNA) | NM_003124 | NM_011467 |
| Refseq (protein) | NP_003115 | NP_035597 |
| Gene locus | Chr 2: 72.89 - 72.89 Mb | Chr 6: 85.13 - 85.14 Mb |
| PubMed search | 6697 |
20751
|
Sepiapterin reductase (SPR) is the enzyme in eukaryotes that the reduction of sepiapterin 6-pyruvoyl-tetrahydropterin and 5,6,7,8- catalyzed . These are the final steps in the biosynthesis of the pterins , which form the framework for several vitamins and cofactors . SPR is localized in the cytoplasm . Mutations in the SPR - gene of man can SPR deficiency, and cause this is a rare inherited disorder.
Occurrence
In the 1960s, an enzyme was obtained and purified from extracts of rat livers which catalyzed the reduction of sepiapterin to dihydrobiopterin. Sepiapterin reductases have also been isolated from insects and from organs of mice, humans and other organisms. The most abundant sources of SPRs are erythrocytes, liver and brain tissue. Some SPRs have been cloned and sequenced. An X-ray structure analysis of the SPR from mice showed that there is a homodimer with 261 amino acids per monomer.
SPR has also been demonstrated in Dictyostelium .
function
biochemistry
Together with the cofactor NADPH , the enzyme catalyzes the reduction (hydrogenation) of the carbonyl group of sepiapterin to 7,8-dihydrobiopterin. In the biosynthesis of 5,6,7,8-Tetrahydrobiopterins it is for the hydrogenation of the precursors, u. a. of 6-pyruvoyl-5,6,7,8-tetrahydropterins responsible.
Position in metabolism
SPR is involved in the synthesis of pigments in the metabolism of many eukaryotes.
In the pterin metabolism of humans , neurotransmitters of the cerebrospinal fluid are produced with the participation of SPR .
Deficiency
A deficiency in SPR has been clinically described as a treatable congenital deficiency of the pterin metabolism. Successful treatment took place over 2–5 years of substitution therapy for affected adolescents.
Individual evidence
- ↑ UniProt P35270
- ↑ Masako Matsubara, Setsuko Katoh, Miki Akino, Seymour Kaufman, Sepiapterin reductase, Biochimica et Biophysica Acta - Enzymology and Biological Oxidation, 122 (2), 202-212 (1966); doi : 10.1016 / 0926-6593 (66) 90062-2 .
- ↑ UniProt entry
- ↑ Günter Auerbach, Anja Herrmann, Markus Gütlich, Markus Fischer, Uwe Jacob, Adelbert Bacher, Robert Huber, The 1.25 Å crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters The EMBO Journal 16, 7219-7230 (1997) ; doi : 10.1093 / emboj / 16.24.7219 .
- ↑ YA Kim, HJ Chung et al. a .: Characterization of recombinant Dictyostelium discoideum sepiapterin reductase expressed in E. coli. In: Molecules and cells. Volume 10, Number 4, August 2000, pp. 405-410, ISSN 1016-8478 . PMID 10987137 .
- ↑ Braasch, Ingo, Manfred Schartl, Jean-Nicolas Volff: Evolution of pigment synthesis pathways by gene and genome duplication in fish. BMC Evolutionary Biology, Volume 7, No. 1, 2007, p. 74.
- ↑ a b Echenne, Bernard et al .: Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy. Pediatric Neurology, Vol. 35, No. 5, 2006, pp. 308-313.
