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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
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MetaCyc Pathway: urate degradation to allantoin I

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/Assimilation Aromatic Compounds Degradation Urate Degradation

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Danio rerio , Delftia acidovorans , Glycine max , Mus musculus , Pseudomonas aeruginosa

Expected Taxonomic Range: Bacteria , Eukaryota

Summary:
The purine degradation pathway plays an important role in nitrogen metabolism in most organisms. The final product of de novo purine biosynthesis, IMP, is degraded through sequential enzymatic steps into urate, which contains a high level of nitrogen [Smith02b] (see purine nucleotides degradation I (plants)). In most organisms, including some bacteria, plants, and certain animals, urate is metabolized via a common pathway, producing the stereospecific form (S)-(+)-allantoin as the final product [Todd06a]. Some organisms that are not able to degrade urate include humans, apes, birds and reptiles [Ramazzina06].

It has previously been thought that allantoin is formed from urate in a single step, catalyzed by sepiapterin reductase. However, it is now established that the process involves three different enzymes [Ramazzina06]. In the first step of the pathway urate is oxidized to 5-hydroxyisourate. The oxidation can be carried out by two distinct enzymes: eukaryotes and some bacteria use EC 1.7.3.3, factor-independent urate hydroxylase, as described in this pathway variant [Modric92, Kahn97], while some prokaryotes possess EC 1.14.13.113, FAD-dependent urate hydroxylase, as described in urate degradation to allantoin II [Michiel12].

5-hydroxyisourate is relatively unstable, and indeed decomposes in vitro to yield allantoin. However, this spontaneous reaction is unlikely to be physiologically relevant, because spontaneous decomposition yields racemic allantoin, while organisms contain mostly the (S)-(+)-allantoin enantiomer.

An enzyme that catalyzes the hydrolysis of the N1-C6 bond of 5-hydroxyisourate, forming 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, has been discovered and isolated from Glycine max [Sarma99]. An enzyme that catalyzes the decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline to (S)-(+)-allantoin was first discovered in mouse [Ramazzina06] and later purified from Arabidopsis thaliana col [Pessoa10, Lamberto10], Bacillus subtilis [Kim07b] and Klebsiella pneumoniae pneumoniae MGH 78578 [French10].

This pathway is part of various metaboilc processes, including both degradative pathways, such as the degradation of purines to glyoxylate and urea or ammonia, and biosynthetic pathways, such as the plant biosynthesis of ureides, which is part of the mechanism used by tropical legumes to trasport the nitrogen fixed by their bacterial symbionts in the root nodules to the rest of the plant (see ureide biosynthesis).

Superpathways: superpathway of purines degradation in plants , ureide biosynthesis

Variants: urate degradation to allantoin II

Credits:
Created 29-Oct-2007 by Caspi R , SRI International


References

French10: French JB, Ealick SE (2010). "Structural and mechanistic studies on Klebsiella pneumoniae 2-Oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase." J Biol Chem 285(46);35446-54. PMID: 20826786

Kahn97: Kahn, K., Serfozo, P., Tipton, P.A. (1997). "Identification of the true product of the urate oxidase reaction." J Am Chem Soc 119: 5435-5442.

Kim07b: Kim K, Park J, Rhee S (2007). "Structural and functional basis for (S)-allantoin formation in the ureide pathway." J Biol Chem 282(32);23457-64. PMID: 17567580

Lamberto10: Lamberto I, Percudani R, Gatti R, Folli C, Petrucco S (2010). "Conserved alternative splicing of Arabidopsis transthyretin-like determines protein localization and S-allantoin synthesis in peroxisomes." Plant Cell 22(5);1564-74. PMID: 20511299

Michiel12: Michiel M, Perchat N, Perret A, Tricot S, Papeil A, Besnard M, de Berardinis V, Salanoubat M, Fischer C (2012). "Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO." Environ Microbiol Rep 4(6);642-7. PMID: 23760935

Modric92: Modric, N., Derome, A.E., Ashcroft, S.J.H., Poje, M. (1992). "Tracing and identification of uricase reaction intermediates." Tetrahedron Lett 33: 6691-6694.

Pessoa10: Pessoa J, Sarkany Z, Ferreira-da-Silva F, Martins S, Almeida MR, Li J, Damas AM (2010). "Functional characterization of Arabidopsis thaliana transthyretin-like protein." BMC Plant Biol 10;30. PMID: 20167108

Ramazzina06: Ramazzina I, Folli C, Secchi A, Berni R, Percudani R (2006). "Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes." Nat Chem Biol 2(3);144-8. PMID: 16462750

Raychaudhuri02: Raychaudhuri A, Tipton PA (2002). "Cloning and expression of the gene for soybean hydroxyisourate hydrolase. Localization and implications for function and mechanism." Plant Physiol 130(4);2061-8. PMID: 12481089

Sarma99: Sarma AD, Serfozo P, Kahn K, Tipton PA (1999). "Identification and purification of hydroxyisourate hydrolase, a novel ureide-metabolizing enzyme." J Biol Chem 274(48);33863-5. PMID: 10567345

Smith02b: Smith PM, Atkins CA (2002). "Purine biosynthesis. Big in cell division, even bigger in nitrogen assimilation." Plant Physiol 128(3);793-802. PMID: 11891236

Todd06a: Todd CD, Tipton PA, Blevins DG, Piedras P, Pineda M, Polacco JC (2006). "Update on ureide degradation in legumes." J Exp Bot 57(1);5-12. PMID: 16317038

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bachrach57: Bachrach, U (1957). "The aerobic breakdown of uric acid by certain pseudomonads." J Gen Microbiol 17(1);1-11. PMID: 13475666

Bergmann83: Bergmann H, Preddie E, Verma DP (1983). "Nodulin-35: a subunit of specific uricase (uricase II) induced and localized in the uninfected cells of soybean nodules." EMBO J 2(12);2333-2339. PMID: 16453488

Bongaerts77: Bongaerts GP, Sin IL, Peters AL, Vogels GD (1977). "Purine degradation in Pseudomonas aeruginosa and Pseudomonas testosteroni." Biochim Biophys Acta 499(1);111-8. PMID: 407941

Kahn97a: Kahn K, Tipton PA (1997). "Kinetic mechanism and cofactor content of soybean root nodule urate oxidase." Biochemistry 1997;36(16);4731-8. PMID: 9125493

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lucas83: Lucas K, Boland MJ, Schubert KR (1983). "Uricase from soybean root nodules: purification, properties, and comparison with the enzyme from cowpea." Arch Biochem Biophys 226(1);190-7. PMID: 6685457

Nguyen85: Nguyen T, Zelechowska M, Foster V, Bergmann H, Verma DP (1985). "Primary structure of the soybean nodulin-35 gene encoding uricase II localized in the peroxisomes of uninfected cells of nodules." Proc Natl Acad Sci U S A 82(15);5040-5044. PMID: 16593585

Pope09: Pope SD, Chen LL, Stewart V (2009). "Purine utilization by Klebsiella oxytoca M5al: genes for ring-oxidizing and -opening enzymes." J Bacteriol 191(3);1006-17. PMID: 19060149

Roberts90a: Roberts W (1890). "On the History of Uric Acid in the Urine, with reference to the Formation of Uric Acid Concretions and Deposits." Med Chir Trans 73;245-71. PMID: 20896767

Saeed04: Saeed HM, Abdel-Fattah YR, Berekaa MM, Gohar YM, Elbaz MA (2004). "Identification, cloning and expression of Pseudomonas aeruginosa Ps-x putative urate oxidase gene in Escherichia coli." Pol J Microbiol 53(4);227-36. PMID: 15790071

Stover00: Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV (2000). "Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen." Nature 406(6799);959-64. PMID: 10984043

Suzuki91a: Suzuki H, Verma DP (1991). "Soybean Nodule-Specific Uricase (Nodulin-35) Is Expressed and Assembled into a Functional Tetrameric Holoenzyme in Escherichia coli." Plant Physiol 95(2);384-389. PMID: 16667995

Vaughn82: Vaughn KC, Duke SO, Duke SH, Henson CA (1982). "Ultrastructural localization of urate oxidase in nodules of Sesbania exaltata, Glycine max, and Medicago sativa." Histochemistry 1982;74(3);309-18. PMID: 7201988


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, BIOCYC13A.