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|
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 [Smith02a] (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 184.108.40.206, factor-independent urate hydroxylase, as described in this pathway variant [Modric92, Kahn97], while some prokaryotes possess EC 220.127.116.11, 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 [Kim07c] and Klebsiella pneumoniae pneumoniae MGH 78578 [French10a].
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).
Variants: urate degradation to allantoin II
French10a: 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
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
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
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
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
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
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