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Literature summary for 1.5.1.34 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

Inhibitors Comment Organism Structure
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
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]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
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
additional information
-
additional information MichaelisMenten kinetics of dihydrofolate reductase-catalyzed (6R)-5,6,7,8-tetrahydro-L-biopterin recycling Homo sapiens

Localization

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens P09417
-
-
Sus scrofa Q8MJ30
-
-

Source Tissue

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

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
DHPR
-
Homo sapiens
DHPR
-
Sus scrofa

Temperature Optimum [°C]

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

pH Optimum

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

Cofactor

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

General Information

General Information Comment Organism
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
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
physiological function the enzyme catalyzes (6R)-5,6,7,8-tetrahydro-L-biopterin recycling in endothelial cytosols Homo sapiens
physiological function the enzyme catalyzes (6R)-5,6,7,8-tetrahydro-L-biopterin recycling in endothelial cytosols with high affinity for dihydrobiopterin Sus scrofa