ArticleProceedings of the National Academy of Sciences of the United States of America2014
Evolutionary history and metabolic insights of ancient mammalian uricases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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
184 citing papers in PubMed, 340 citations in OpenAlex.
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.American journal of hypertension · 2017Trial
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Antioxidant malic-acid-derived lipid nanoparticles delivering secretory uricase circRNA for hyperuricemia and complication management in mice.Nature communications · 2026Article
- Article
- Extracellular urate oxidase from Arthrobacter creatinolyticus SA1: statistical optimization, purification, and in-vitro evaluation of antihyperuricemic activity.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- Therapeutic Strategies for Hyperuricemia: From Small-Molecule Inhibitors to RNA Therapeutics.ACS pharmacology & translational science · 2026Review
- Periplasmic detoxification of urate hydroperoxide underpinsbioRxiv : the preprint server for biology · 2026Article
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Resolving competing evolutionary histories in joint ancestral state reconstruction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SLC52A1 is a neofunctionalized primate urate transporter enabling intestinal urate secretion.The Journal of biological chemistry · 2026Article
- Review
- Biosynthesized uricase with dual-terminus zwitterionic EKylation for prolonged elimination half-life and reduced immunogenicity.Journal of biological engineering · 2026Article
- Establishment of a novel cynomolgus monkey model of hyperuricemia.Animal models and experimental medicine · 2026Article
- The histone code at a crossroads: history, context, and new approaches.Trends in genetics : TIG · 2026Review
- Early urate-lowering therapy and cardiometabolic risk in adults without documented major cardiometabolic disease: a real-world cohort study.Frontiers in endocrinology · 2026Article
- Research progress on the correlation between gut microbiota and the occurrence of hyperuricemia.Frontiers in microbiology · 2026Review
- Kinetic and thermostability modulation ofVeterinary research forum : an international quarterly journal · 2026Article
- New Insight Into Male Infertility: Deviation From Basic Tenets of Life.Oxidative medicine and cellular longevity · 2026Review
- Uricolysis by Arthrobacter globiformis uricase: structural basis for its catalytic activity and thermostability.Acta pharmacologica Sinica · 2025Article
124 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Uricase is an enzyme involved in purine catabolism and is found in all three domains of life. Curiously, uricase is not functional in some organisms despite its role in converting highly insoluble uric acid into 5-hydroxyisourate. Of particular interest is the observation that apes, including humans, cannot oxidize uric acid, and it appears that multiple, independent evolutionary events led to the silencing or pseudogenization of the uricase gene in ancestral apes. Various arguments have been made to suggest why natural selection would allow the accumulation of uric acid despite the physiological consequences of crystallized monosodium urate acutely causing liver/kidney damage or chronically causing gout. We have applied evolutionary models to understand the history of primate uricases by resurrecting ancestral mammalian intermediates before the pseudogenization events of this gene family. Resurrected proteins reveal that ancestral uricases have steadily decreased in activity since the last common ancestor of mammals gave rise to descendent primate lineages. We were also able to determine the 3D distribution of amino acid replacements as they accumulated during evolutionary history by crystallizing a mammalian uricase protein. Further, ancient and modern uricases were stably transfected into HepG2 liver cells to test one hypothesis that uricase pseudogenization allowed ancient frugivorous apes to rapidly convert fructose into fat. Finally, pharmacokinetics of an ancient uricase injected in rodents suggest that our integrated approach provides the foundation for an evolutionarily-engineered enzyme capable of treating gout and preventing tumor lysis syndrome in human patients.
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.