ArticleBiochimie2018
L-ascorbic acid: A true substrate for HIF prolyl hydroxylase?
Article in Biochimie, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Pregnancy-related disorders: molecular mechanisms and management.Molecular biomedicine · 2026Review
- Sodium ascorbate versus ascorbic acid in sepsis: a narrative review of emerging cardiovascular and neurological benefits.Critical care (London, England) · 2026Review
- The potentially therapeutic effects of ascorbic acid in different cell line in attempt to reduce the risk of radiation therapy.Scientific reports · 2025Article
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma.Journal of personalized medicine · 2024Article
- Integrated transcriptomic analysis and machine learning for characterizing diagnostic biomarkers and immune cell infiltration in fetal growth restriction.Frontiers in immunology · 2024Article
- Unraveling the 2,3-diketo-L-gulonic acid-dependent and -independent impacts of L-ascorbic acid on somatic cell reprogramming.Cell & bioscience · 2023Article
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2.Molecules (Basel, Switzerland) · 2022Article
- Structure and Function of TET Enzymes.Advances in experimental medicine and biology · 2022Article
- Review
- Epigenetic Regulation of Genomic Stability by Vitamin C.Frontiers in genetics · 2021Review
- Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment.Oncology letters · 2021Article
- Kinetic parameters of human aspartate/asparagine-β-hydroxylase suggest that it has a possible function in oxygen sensing.The Journal of biological chemistry · 2020Article
- HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons.Frontiers in pharmacology · 2020Review
- Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives.European journal of medicinal chemistry · 2019Article
- Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism.International journal of molecular sciences · 2019Article
- 4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1α, which is attenuated by ascorbate.The Journal of antibiotics · 2019Article
- Vitamin C effects on 5-hydroxymethylcytosine and gene expression in osteoblasts and chondrocytes: Potential involvement of PHD2.PloS one · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
L-Ascorbate (L-Asc), but not D-isoascorbate (D-Asc) and N-acetylcysteine (NAC) suppress HIF1 ODD-luc reporter activation induced by various inhibitors of HIF prolyl hydroxylase (PHD). The efficiency of suppression by L-Asc was sensitive to the nature of HIF PHD inhibitor chosen for reporter activation. In particular, the inhibitors developed to compete with alpha-ketoglutarate (αKG), were less sensitive to suppression by the physiological range of L-Asc (40-100 μM) than those having a strong iron chelation motif. Challenging those HIF activators in the reporter system with D-Asc demonstrated that the D-isomer, despite exhibiting the same reducing potency with respect to ferric iron, had almost no effect compared to L-Asc. Similarly, no effect on reporter activation was observed with cell-permeable reducing agent NAC up to 1 mM. Docking of L-Asc and D-Asc acid into the HIF PHD2 crystal structure showed interference of Tyr310 with respect to D-Asc. This suggests that L-Asc is not merely a reducing agent preventing enzyme inactivation. Rather, the overall results identify L-Asc as a co-substrate of HIF PHD that may compete for the binding site of αKG in the enzyme active center. This conclusion is in agreement with the results obtained recently in cell-based systems for TET enzymes and jumonji histone demethylases, where L-Asc has been proposed to act as a co-substrate and not as a reducing agent preventing enzyme inactivation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.