Evidence map›Paper›PMID 27922051›Full record

ArticleScientific reports2016

Catalysis and Structure of Zebrafish Urate Oxidase Provide Insights into the Origin of Hyperuricemia in Hominoids.

Marialaura Marchetti, Anastasia Liuzzi, Beatrice Fermi, Romina Corsini, Claudia Folli, Valentina Speranzini, Francesco Gandolfi, Stefano Bettati, Luca Ronda, Laura Cendron and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Identification of hidden associations among eukaryotic genes through statistical analysis of coevolutionary transitions.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Marialaura MarchettiDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Anastasia LiuzziDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Beatrice FermiDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Romina CorsiniDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Claudia FolliDepartment of Food Science University of Parma, 43124, Parma, Italy.
Valentina SperanziniDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Francesco GandolfiDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Stefano BettatiDepartment of Neurosciences, University of Parma, 43124, Parma, Italy.
Luca RondaDepartment of Neurosciences, University of Parma, 43124, Parma, Italy.
Laura CendronDepartment of Biology, University of Padova, 35121, Padova, Italy.
Rodolfo BerniDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
Giuseppe ZanottiDepartment of Biology, University of Padova, 35121, Padova, Italy.
Riccardo PercudaniDepartment of Life Sciences, University of Parma, 43124, Parma, Italy.
University of Parma · ITUniversity of Padua · IT

Funding

Telethon GGP13149
6 · The paper itself

Abstract

Urate oxidase (Uox) catalyses the first reaction of oxidative uricolysis, a three-step enzymatic pathway that allows some animals to eliminate purine nitrogen through a water-soluble compound. Inactivation of the pathway in hominoids leads to elevated levels of sparingly soluble urate and puts humans at risk of hyperuricemia and gout. The uricolytic activities lost during evolution can be replaced by enzyme therapy. Here we report on the functional and structural characterization of Uox from zebrafish and the effects on the enzyme of the missense mutation (F216S) that preceded Uox pseudogenization in hominoids. Using a kinetic assay based on the enzymatic suppression of the spectroscopic interference of the Uox reaction product, we found that the F216S mutant has the same turnover number of the wild-type enzyme but a much-reduced affinity for the urate substrate and xanthine inhibitor. Our results indicate that the last functioning Uox in hominoid evolution had an increased Michaelis constant, possibly near to upper end of the normal range of urate in the human serum (~300 μM). Changes in the renal handling of urate during primate evolution can explain the genetic modification of uricolytic activities in the hominoid lineage without the need of assuming fixation of deleterious mutations.

Indexed as

Mutation, MissenseAmino Acid SequenceAnimalsBase SequenceBinding SitesBiocatalysisBiological EvolutionCrystallography, X-RayGene ExpressionHumansHylobatesHyperuricemiaKineticsMacaca fascicularisModels, MolecularProtein BindingRecombinant ProteinsUrate OxidaseUric Acid

Identifiers

PMID27922051
PMCPMC5138847
OpenAlexW2560476695

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.