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Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes.

Abstract：

:Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the mechanism and regiochemistry of urate oxidation have called this assumption into question, suggesting the existence of other distinct enzymatic activities. Through phylogenetic genome comparison, we identify here two genes that share with urate oxidase a common history of loss or gain events. We show that the two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU): hydrolysis of HIU to give 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and decarboxylation of OHCU to give S-(+)-allantoin. Urate oxidation produces racemic allantoin on a time scale of hours, whereas the full enzymatic complement produces dextrorotatory allantoin on a time scale of seconds. The use of these enzymes in association with urate oxidase could improve the therapy of hyperuricemia.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Ramazzina I,Folli C,Secchi A,Berni R,Percudani R

doi

10.1038/nchembio768

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

144-8

issue

3

eissn

1552-4450

issn

1552-4469

pii

nchembio768

journal_volume

2

pub_type

杂志文章

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