ArticleProceedings of the National Academy of Sciences of the United States of America2020
Physiological levels of folic acid reveal purine alterations in Lesch-Nyhan disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review.Cells · 2021Pooled it
- Changes in Purine Metabolism During Differentiation of Dopamine Neurons from Human Induced Pluripotent Stem Cells.Cellular and molecular neurobiology · 2026Article
- Vitamin B12 and Reproductive Health: Clinical Insights, Emerging Mechanistic Understanding, and Nutritional Aspects.Molecular reproduction and development · 2026Review
- Gene Expression Analysis of HPRT-Deficient Cells Maintained with Physiological Levels of Folic Acid.Cells · 2025Article
- Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.Acta pharmacologica Sinica · 2025Review
- Article
- A new physiological medium uncovers biochemical and cellular alterations in Lesch-Nyhan disease fibroblasts.Molecular medicine (Cambridge, Mass.) · 2024Article
- Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.Nutrients · 2023Review
- Purine Nucleotide Alterations in Tumoral Cell Lines Maintained with Physiological Levels of Folic Acid.International journal of molecular sciences · 2023Article
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism.Journal of translational medicine · 2023Article
- Comparative study and relationship analysis between purine content, uric acid, superoxide dismutase, and growth traits in purebred and crossbred Thai native chickens.Frontiers in veterinary science · 2023Article
- HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch-Nyhan disease.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media. Thus, physiological levels of folic acid induce accumulation of 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP), an intermediary of de novo purine biosynthetic pathway, and depletion of ATP. Additionally, Z-nucleotide derivatives (AICAr, AICA) are detected at high levels in the urine of patients with LND and its variants (hypoxanthine-guanine phosphoribosyltransferase [HGprt]-related neurological dysfunction and HGprt-related hyperuricemia), and the ratio of AICAr/AICA is significantly increased in patients with neurological problems (LND and HGprt-related neurological dysfunction). Moreover, AICAr is present in the cerebrospinal fluid of patients with LND, but not in control individuals. We hypothesize that purine alterations detected in LND fibroblasts may also occur in the brain of patients with LND.
Indexed as
Identifiers
What OpenQuestion holds
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.