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Literature summary for 1.1.1.153 extracted from
- Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase (2015), J. Pharmacol. Exp. Ther., 352, 529-540.
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| Chlorpropamide | noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens |  |
| Chlorpropamide | - |
Rattus norvegicus | |
| glibenclamide | noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| glibenclamide | - |
Rattus norvegicus | |
| additional information | sulfonylurea- or sulfonamide-based drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase | Homo sapiens | |
| additional information | sulfonylurea- or sulfonamide-based drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase | Rattus norvegicus | |
| sulfamethoxazole | noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| sulfamethoxazole | - |
Rattus norvegicus | |
| sulfapyridine | noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| sulfapyridine | - |
Rattus norvegicus | |
| sulfasalazine | noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| sulfasalazine | - |
Rattus norvegicus | |
| sulfathiazole | noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| sulfathiazole | - |
Rattus norvegicus | |
| Tolbutamide | noncompetitive inhibition in sepiapterin reduction and redox cycling | Homo sapiens | |
| Tolbutamide | - |
Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| sepiapterin + NADPH + H+ | Homo sapiens | no stereochemic specification in the publication | 7,8-dihydrobiopterin + NADP+ | - |
? | |
| sepiapterin + NADPH + H+ | Rattus norvegicus | no stereochemic specification in the publication | 7,8-dihydrobiopterin + NADP+ | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P35270 | - |
- |
| Rattus norvegicus | P18297 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| PC-12 cell | - |
Homo sapiens | - |
| PC-12 cell | - |
Rattus norvegicus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the enzyme's one-electron reduction of redox cycling chemicals, such as menadione, generates radical cations. The rapid reaction of these cations with molecular oxygen regenerates the redox active chemical, and in the process superoxide anion is formed. Sepiapterin reduction is catalyzed by NADPH, whereas chemical redox cycling is catalyzed by NADPH and/or NADH, overview | Homo sapiens | ? | - |
? | |
| additional information | the enzyme's one-electron reduction of redox cycling chemicals, such as menadione, generates radical cations. The rapid reaction of these cations with molecular oxygen regenerates the redox active chemical, and in the process superoxide anion is formed. Sepiapterin reduction is catalyzed by NADPH, whereas chemical redox cycling is catalyzed by NADPH and/or NADH, overview | Rattus norvegicus | ? | - |
? | |
| sepiapterin + NADPH + H+ | no stereochemic specification in the publication | Homo sapiens | 7,8-dihydrobiopterin + NADP+ | - |
? | |
| sepiapterin + NADPH + H+ | no stereochemic specification in the publication | Rattus norvegicus | 7,8-dihydrobiopterin + NADP+ | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| sepiapterin reductase | - |
Homo sapiens |
| sepiapterin reductase | - |
Rattus norvegicus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
| 37 | - |
assay at | Rattus norvegicus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6.4 | - |
assay at, sepiapterin reduction | Homo sapiens |
| 6.4 | - |
assay at, sepiapterin reduction | Rattus norvegicus |
| 7.4 | - |
in vivo assay at, sepiapterin reduction | Rattus norvegicus |
| 7.8 | - |
assay at, one-electron reduction of redox cycling menadione | Homo sapiens |
| 7.8 | - |
assay at, one-electron reduction of redox cycling menadione | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Rattus norvegicus | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000031 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | sulfasalazine | |
| 0.000031 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | sulfasalazine | |
| 0.000062 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | sulfathiazole | |
| 0.000062 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | sulfathiazole | |
| 0.00012 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | Chlorpropamide | |
| 0.00012 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | Chlorpropamide | |
| 0.000141 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | sulfapyridine | |
| 0.000141 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | sulfapyridine | |
| 0.00018 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | sulfamethoxazole | |
| 0.00018 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | sulfamethoxazole | |
| 0.00034 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | glibenclamide | |
| 0.00037 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | Chlorpropamide | |
| 0.00051 | - |
pH 6.4, 37°C, sepiapterin reduction | Homo sapiens | Tolbutamide | |
| 0.00053 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | sulfasalazine | |
| 0.00111 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | glibenclamide | |
| 0.00458 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | Tolbutamide | |
| 0.00802 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | sulfathiazole | |
| 0.011 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | sulfamethoxazole | |
| 0.0194 | - |
pH 6.4, 37°C, redox cycling | Homo sapiens | sulfapyridine | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| additional information | enzyme three-dimensional structure molecular modeling and docking using crystal structures of SPR, PDB IDs 1SEP, 1NAS, 4HWK, 4J7U, and 4J7X, and the structure of menadione, PDB ID 2QR2, overview | Homo sapiens |
| physiological function | in PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibit both dihydrobiopterin/tetrahydrobiopterin biosynthesis and redox cycling mediated by sepiapterin reductase. Inhibition of dihydrobiopterin/tetrahydrobiopterin biosynthesis results in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine | Homo sapiens |
| physiological function | using NADPH as a source of reducing equivalents, sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), a precursor for tetrahydrobiopterin (BH4). Reduction of sepiapterin generates 7,8-dihydrobiopterin, which is converted to (6R)-5,6,7,8-tetrahydrobiopterin by additional cellular reductases | Homo sapiens |
| physiological function | using NADPH as a source of reducing equivalents, sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), a precursor for tetrahydrobiopterin (BH4). Reduction of sepiapterin generates 7,8-dihydrobiopterin, which is converted to (6R)-5,6,7,8-tetrahydrobiopterin by additional cellular reductases | Rattus norvegicus |
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