PUBLICATION
Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes
- Authors
- Ramazzina, I., Folli, C., Secchi, A., Berni, R., and Percudani, R.
- ID
- ZDB-PUB-070404-1
- Date
- 2006
- Source
- Nature Chemical Biology 2(3): 144-148 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Allantoin/chemical synthesis
- Allantoin/chemistry
- Allantoin/metabolism
- Amidohydrolases/chemistry
- Amidohydrolases/genetics
- Amino Acid Sequence
- Animals
- Carboxy-Lyases/chemistry
- Carboxy-Lyases/genetics
- Catalysis
- Conserved Sequence
- Genome*
- Imidazolines/chemistry
- Mice
- Molecular Conformation
- Molecular Sequence Data
- Molecular Structure
- Oxidation-Reduction
- Phylogeny*
- Stereoisomerism
- Urate Oxidase/chemistry
- Urea/analogs & derivatives
- Urea/chemistry
- Uric Acid/analogs & derivatives
- Uric Acid/chemistry
- Uric Acid/metabolism*
- PubMed
- 16462750 Full text @ Nat. Chem. Biol.
Citation
Ramazzina, I., Folli, C., Secchi, A., Berni, R., and Percudani, R. (2006) Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes. Nature Chemical Biology. 2(3):144-148.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping