ArticleThe Journal of biological chemistry2011
Urate as a physiological substrate for myeloperoxidase: implications for hyperuricemia and inflammation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.BMJ (Clinical research ed.) · 2017Pooled it
- Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double-blind, crossover study.Physiological reports · 2021Trial
- Safety, tolerability, pharmacokinetics and effect on serum uric acid of the myeloperoxidase inhibitor AZD4831 in a randomized, placebo-controlled, phase I study in healthy volunteers.British journal of clinical pharmacology · 2019Trial
- β2 integrin-mediated cell-cell contact transfers active myeloperoxidase from neutrophils to endothelial cells.The Journal of biological chemistry · 2013Trial
- Redox protection by bacterial glutathione peroxidase drives virulence inRedox report : communications in free radical research · 2026Article
- Periplasmic detoxification of urate hydroperoxide underpinsbioRxiv : the preprint server for biology · 2026Article
- Soluble uric acid suppresses neutrophil-mediated host defense in sepsis.Nature communications · 2026Article
- Is uric acid a true antioxidant? Identification of uric acid oxidation products and their biological effects.Redox report : communications in free radical research · 2025Review
- Biomarkers of Oxidative and Mitochondrial Stress Are Associated With Accelerated Pace of Aging at Midlife in a Birth Cohort.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- The prognostic value of admission serum uric acid for acute kidney injury: a two-center retrospective analysis.Frontiers in molecular biosciences · 2025Article
- Metabolic Pathways Affected in Patients Undergoing Hemodialysis and Their Relationship with Inflammation.International journal of molecular sciences · 2024Article
- Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.Journal of medicinal chemistry · 2024Article
- Expression of RcrB confers resistance to hypochlorous acid in uropathogenicJournal of bacteriology · 2023Article
- Expression of RcrB confers resistance to hypochlorous acid in uropathogenicbioRxiv : the preprint server for biology · 2023Article
- Peroxiredoxin 2: An Important Element of the Antioxidant Defense of the Erythrocyte.Antioxidants (Basel, Switzerland) · 2023Review
- A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis.Journal of orthopaedic surgery and research · 2023Article
- Investigating a possible causal relationship between maternal serum urate concentrations and offspring birthweight: a Mendelian randomization study.International journal of epidemiology · 2023Article
- Uric Acid Reacts with Peroxidasin, Decreases Collagen IV Crosslink, Impairs Human Endothelial Cell Migration and Adhesion.Antioxidants (Basel, Switzerland) · 2022Article
- Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces.Antioxidants (Basel, Switzerland) · 2021Review
- The Dual Role of Myeloperoxidase in Immune Response.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MPO were reduced by urate with rate constants of 4.6 × 10(5) M(-1) s(-1) for compound I and 1.7 × 10(4) M(-1) s(-1) for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted super-stoichiometric consumption of glutathione, which indicates that it is converted to a free radical intermediate. In combination with superoxide and hydrogen peroxide, MPO oxidized urate to a reactive hydroperoxide. This would form by addition of superoxide to the urate radical. Urate also enhanced MPO-dependent consumption of nitric oxide. In human plasma, stimulated neutrophils produced allantoin in a reaction dependent on the NADPH oxidase, MPO and superoxide. We propose that urate is a physiological substrate for MPO that is oxidized to the urate radical. The reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease.
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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.