Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans

@article{Lee2013CharacterizationOT,
  title={Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans},
  author={I. Russel Lee and Liting Yang and Gaseene Sebetso and R Allen and Thien V.H. Doan and Ross Blundell and Edmund Yan Long Lui and Carl A. Morrow and James Angus Fraser},
  journal={PLoS ONE},
  year={2013},
  volume={8}
}
Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In… 

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References

SHOWING 1-10 OF 73 REFERENCES
Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes
TLDR
Through phylogenetic genome comparison, this work identifies here two genes that share with urate oxidase a common history of loss or gain events and shows that the two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU): hydrolysis of HIU and decarboxylation of OHCU to give S-allantoin.
Urease as a Virulence Factor in Experimental Cryptococcosis
TLDR
The results suggest that urease activity is involved in the pathogenesis of cryptococcosis but that the importance may be species and/or infection site specific.
Nitrogen Metabolite Repression of Metabolism and Virulence in the Human Fungal Pathogen Cryptococcus neoformans
TLDR
Evidence is provided of genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen Cryptococcus neoformans, and of Gat1, which plays a complex regulatory role during infection.
Growth of Cryptococcus neoformans on uric acid agar.
  • F. Staib, S. Mishra, T. Able, A. Blisse
  • Biology
    Zentralblatt fur Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene. Erste Abteilung Originale. Reihe A: Medizinische Mikrobiologie und Parasitologie
  • 1976
Effect of certain low molecular nitrogen substances, namely uric acid, eura and creatinine as sole source of nitrogen was studied on 31 strains of Cryptococcus neoformans as well as on a rough
Evolution of urate-degrading enzymes in animal peroxisomes
TLDR
It is suggested that amphibian urate oxidase is a transition form in the evolution of aquatic animals to land animals, and changes of allantoinase and allantoicase in molecular structure and intracellular localization during animal evolution may be as follows.
Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase
TLDR
Transcriptional activity of CNLAC1 was found to be derepressed in the absence of glucose and to correspond to an increase in enzymatic activity.
Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family.
TLDR
The PucM structure determined for theTRP family leads to the conclusion that diverse members of the TRP family would function similarly to Puc M as HIU hydrolase.
Iron Source Preference and Regulation of Iron Uptake in Cryptococcus neoformans
TLDR
Results indicate that C. neoformans utilizes iron sources within the host that require Cft1 and a reductive iron uptake system, suggesting a requirement for reductiveIron acquisition during cryptococcal meningitis.
Cyclic AMP-Dependent Protein Kinase Controls Virulence of the Fungal Pathogen Cryptococcus neoformans
TLDR
A Gα protein-cAMP-PKA signaling pathway regulating differentiation and virulence of a human fungal pathogen is defined, showing that the Pka1 catalytic subunit functions downstream of the Pkr1 regulatory subunit.
...
...