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Literature summary extracted from

  • Schmidt, K.; Kolesnik, B.; Gorren, A.; Werner, E.; Mayer, B.
    Cell type-specific recycling of tetrahydrobiopterin by dihydrofolate reductase explains differential effects of 7,8-dihydrobiopterin on endothelial nitric oxide synthase uncoupling (2014), Biochem. Pharmacol., 90, 246-253 .
    View publication on PubMedView publication on EuropePMC

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.34 aminopterin the DHFR inhibitor aminopterin inhibits tetrahydrobiopterin recycling. Aminopterin has no effect alone but slightly reduced L-citrulline formation and cGMP accumulation in the presence of dihydrobiopterin Homo sapiens
1.5.1.34 aminopterin the DHFR inhibitor aminopterin inhibits tetrahydrobiopterin recycling. Aminopterin has no effect alone but slightly reduced L-citrulline formation and cGMP accumulation in the presence of dihydrobiopterin Sus scrofa

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.5.1.34 additional information
-
additional information Michaelis-Menten kinetics of dihydrofolate reductase-catalyzed (6R)-5,6,7,8-tetrahydro-L-biopterin recycling, the enzyme shows high affinity for dihydrobiopterin Sus scrofa
1.5.1.34 additional information
-
additional information MichaelisMenten kinetics of dihydrofolate reductase-catalyzed (6R)-5,6,7,8-tetrahydro-L-biopterin recycling Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.5.1.34 cytosol
-
Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.34 6,7-dihydropteridine + NADPH + H+ Homo sapiens
-
5,6,7,8-tetrahydropteridine + NADP+
-
r
1.5.1.34 6,7-dihydropteridine + NADPH + H+ Sus scrofa
-
5,6,7,8-tetrahydropteridine + NADP+
-
r

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.34 Homo sapiens P09417
-
-
1.5.1.34 Sus scrofa Q8MJ30
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.5.1.34 aorta
-
Sus scrofa
-
1.5.1.34 endothelial cell
-
Homo sapiens
-
1.5.1.34 endothelial cell aortic Sus scrofa
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.34 6,7-dihydropteridine + NADPH + H+
-
Homo sapiens 5,6,7,8-tetrahydropteridine + NADP+
-
r
1.5.1.34 6,7-dihydropteridine + NADPH + H+
-
Sus scrofa 5,6,7,8-tetrahydropteridine + NADP+
-
r

Synonyms

EC Number Synonyms Comment Organism
1.5.1.34 DHPR
-
Homo sapiens
1.5.1.34 DHPR
-
Sus scrofa

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.5.1.34 37
-
assay at Homo sapiens
1.5.1.34 37
-
assay at Sus scrofa

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.34 7.4
-
assay at Homo sapiens
1.5.1.34 7.4
-
assay at Sus scrofa

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.34 NADP+
-
Homo sapiens
1.5.1.34 NADP+
-
Sus scrofa
1.5.1.34 NADPH
-
Homo sapiens
1.5.1.34 NADPH
-
Sus scrofa

General Information

EC Number General Information Comment Organism
1.5.1.34 metabolism inhibition of de novo biosynthesis of tetrahydrobiopterin by preincubating the cells for 24 h with the GTP cyclohydrolase inhibitor DAHP (10 mM) diminishes L-citrulline formation. Addition of dihydrobiopterin fully restores L-citrulline formation. In addition to its effect on arginine-to-citrulline conversion, pretreatment of the cells with DAHP reduces A23187-induced cGMP accumulation. Addition of tetrahydrobiopterin or dihydrobiopterin not only antagonizes the inhibitory effect of DAHP but also increases cGMP accumulation. (6R)-5,6,7,8-Tetrahydro-L-biopterin availability regulates nitric oxide and superoxide formation by endothelial nitric oxide synthase (eNOS). At low tetrahydrobiopterin or low tetrahydrobiopterin to 7,8-dihydrobiopterin ratios the enzyme becomes uncoupled and generates superoxide at the expense of NO Sus scrofa
1.5.1.34 metabolism inhibition of de novo biosynthesis of tetrahydrobiopterin by preincubating the cells for 24 h with the GTP cyclohydrolase inhibitor dihydroxyacetone phosphate (10 mM) diminishes L-citrulline formation. Addition of dihydrobiopterin fully restores L-citrulline formation. In addition to its effect on arginine-to-citrulline conversion, pretreatment of the cells with dihydroxyacetone phosphate reduces A23187-induced cGMP accumulation. Addition of tetrahydrobiopterin or dihydrobiopterin not only antagonizes the inhibitory effect of dihydroxyacetone phosphate but also increases cGMP accumulation. (6R)-5,6,7,8-Tetrahydro-L-biopterin availability regulates nitric oxide and superoxide formation by endothelial nitric oxide synthase (eNOS). At low tetrahydrobiopterin or low tetrahydrobiopterin to 7,8-dihydrobiopterin ratios the enzyme becomes uncoupled and generates superoxide at the expense of NO Homo sapiens
1.5.1.34 physiological function the enzyme catalyzes (6R)-5,6,7,8-tetrahydro-L-biopterin recycling in endothelial cytosols Homo sapiens
1.5.1.34 physiological function the enzyme catalyzes (6R)-5,6,7,8-tetrahydro-L-biopterin recycling in endothelial cytosols with high affinity for dihydrobiopterin Sus scrofa