ArticleBiochemical pharmacology2014
Cell type-specific recycling of tetrahydrobiopterin by dihydrofolate reductase explains differential effects of 7,8-dihydrobiopterin on endothelial nitric oxide synthase uncoupling.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Folic Acid and Endothelial Dysfunction in COVID-19.Life (Basel, Switzerland) · 2026Review
- A Reappraisal of the Utility of L-012 to Measure Superoxide from Biologically Relevant Sources.Antioxidants (Basel, Switzerland) · 2023Article
- Uncoupled nitric oxide synthase activity promotes colorectal cancer progression.Frontiers in oncology · 2023Article
- Tetrahydrobiopterin paradoxically mediates cardiac oxidative stress and mitigates ethanol-evoked cardiac dysfunction in conscious female rats.European journal of pharmacology · 2021Article
- Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling.Antioxidants (Basel, Switzerland) · 2021Article
- Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.Current neuropharmacology · 2021Review
- Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BHFrontiers in pharmacology · 2021Article
- The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia.Frontiers in pharmacology · 2020Review
- Evidence of a Role for One-Carbon Metabolism in Blood Pressure: Can B Vitamin Intervention Address the Genetic Risk of Hypertension Owing to a Common Folate Polymorphism?Current developments in nutrition · 2020Review
- Nitric oxide donor [Ru(terpy)(bdq)NO]Free radical biology & medicine · 2017Article
- Organic anion transporters, OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess.Molecular and cellular biochemistry · 2017Article
- Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.Free radical biology & medicine · 2016Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
(6R)-5,6,7,8-Tetrahydro-L-biopterin (BH4) availability regulates nitric oxide and superoxide formation by endothelial nitric oxide synthase (eNOS). At low BH4 or low BH4 to 7,8-dihydrobiopterin (BH2) ratios the enzyme becomes uncoupled and generates superoxide at the expense of NO. We studied the effects of exogenously added BH2 on intracellular BH4/BH2 ratios and eNOS activity in different types of endothelial cells. Incubation of porcine aortic endothelial cells with BH2 increased BH4/BH2 ratios from 8.4 (controls) and 0.5 (BH4-depleted cells) up to ~20, demonstrating efficient reduction of BH2. Uncoupled eNOS activity observed in BH4-depleted cells was prevented by preincubation with BH2. Recycling of BH4 was much less efficient in human endothelial cells isolated from umbilical veins or derived from dermal microvessels (HMEC-1 cells), which exhibited eNOS uncoupling and low BH4/BH2 ratios under basal conditions and responded to exogenous BH2 with only moderate increases in BH4/BH2 ratios. The kinetics of dihydrofolate reductase-catalyzed BH4 recycling in endothelial cytosols showed that the apparent BH2 affinity of the enzyme was 50- to 300-fold higher in porcine than in human cell preparations. Thus, the differential regulation of eNOS uncoupling in different types of endothelial cells may be explained by striking differences in the apparent BH2 affinity of dihydrofolate reductase.
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