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Pathway Description
Purine Nucleotides Degradation II (aerobic)
Homo sapiens
Metabolic Pathway
Purine degradation to urate plays an important role in nitrogen metabolism in homo sapiens. This pathway starts with 3 similar branching pathways, all ending in the synthesis of xanthine. The first pathway starts with adenosine monophosphate (AMP) which is catalyzed by cytosolic 5'-nucleotidase 1A and 5'-nucleotidase to make adenosine. Adenosine is then catalyzed by adenosine deaminase with water and a proton to make inosine with a byproduct of ammonium. Inosine along with a phosphate is catalyzed by purine nucleoside phosphorylase to make hypoxathine with a byproduct of α-D-ribose-1-phosphate. This part of the pathway ends with hypoxathine being catalyzed by xanthine dehydrogenase to synthesize xanthine.
The second part of the pathway starts with guanosine monophosphate (GMP) being catalyzed by cytosolic 5'-nucleotidase II and 5'-nucleotidase into guanosine. The same enzymes that catalyzed adenosine monophosphate to adenosine. Then guanosine is catalyzed by purine nucleoside phosphorylase and an added phosphate to make guanine with the byproduct of α-D-ribose-1-phosphate again. Guanine is then catalyzed by guanine deaminase and synthesizes xanthine with a byproduct of ammonium.
The third part of this pathway starts with inosine monophosphate (IMP) along with NAD and water being catalyzed by inosine-5'-monophosphate dehydrogenase 1 and inosine-5'-monophosphate dehydrogenase 2 to make xanthosine 5-phosphate (XMP) with a byproduct of NADH and a proton. Both inosine-5'-monophosphate dehydrogenase 1 and 2 are inhibited by ppGpp or GMP, stopping this part of the pathway from occuring. XMP will be catalyzed by cytosolic 5'-nucleotidase II and 5'-nucleotidase to make xanthosine. Xanthosine with a phosphate is then catalyzed by purine nucleoside phosphorylase to make xanthine with a byproduct of α-D-ribose-1-phosphate.
Once xanthine is synthesized in any of these three processes, it, with NAD and water, is catalyzed by xanthine dehydrogenase to synthesize urate or uric acid with a byproduct of NADH and a proton.
References
Purine Nucleotides Degradation II (aerobic) References
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Anzai N, Enomoto A, Endou H: Renal urate handling: clinical relevance of recent advances. Curr Rheumatol Rep. 2005 Jun;7(3):227-34. doi: 10.1007/s11926-996-0044-0.
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Pubmed: 6262603
George J, Struthers AD: Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag. 2009;5(1):265-72. doi: 10.2147/vhrm.s4265. Epub 2009 Apr 8.
Pubmed: 19436671
Johnson RJ, Sautin YY, Oliver WJ, Roncal C, Mu W, Gabriela Sanchez-Lozada L, Rodriguez-Iturbe B, Nakagawa T, Benner SA: Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society? J Comp Physiol B. 2009 Jan;179(1):67-76. doi: 10.1007/s00360-008-0291-7. Epub 2008 Jul 23.
Pubmed: 18649082
Kulikowska E, Kierdaszuk B, Shugar D: Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways. Acta Biochim Pol. 2004;51(2):493-531. doi: 035001493.
Pubmed: 15218545
Mohamedali KA, Guicherit OM, Kellems RE, Rudolph FB: The highest levels of purine catabolic enzymes in mice are present in the proximal small intestine. J Biol Chem. 1993 Nov 5;268(31):23728-33.
Pubmed: 8226898
Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T: Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 2008 Jul;275(13):3278-89. doi: 10.1111/j.1742-4658.2008.06489.x. Epub 2008 May 30.
Pubmed: 18513323
Pauly DF, Pepine CJ: D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000 Oct;5(4):249-58. doi: 10.1054/JCPT.2000.18011.
Pubmed: 11150394
Pope SD, Chen LL, Stewart V: Purine utilization by Klebsiella oxytoca M5al: genes for ring-oxidizing and -opening enzymes. J Bacteriol. 2009 Feb;191(3):1006-17. doi: 10.1128/JB.01281-08. Epub 2008 Dec 5.
Pubmed: 19060149
Roberts EL: Guanosine deaminase in human serum and tissue extracts--a reappraisal of the products. Br J Biomed Sci. 2003;60(4):197-203. doi: 10.1080/09674845.2003.11783699.
Pubmed: 14725335
Schultz AC, Nygaard P, Saxild HH: Functional analysis of 14 genes that constitute the purine catabolic pathway in Bacillus subtilis and evidence for a novel regulon controlled by the PucR transcription activator. J Bacteriol. 2001 Jun;183(11):3293-302. doi: 10.1128/JB.183.11.3293-3302.2001.
Pubmed: 11344136
Simoni RE, Gomes LN, Scalco FB, Oliveira CP, Aquino Neto FR, de Oliveira ML: Uric acid changes in urine and plasma: an effective tool in screening for purine inborn errors of metabolism and other pathological conditions. J Inherit Metab Dis. 2007 Jun;30(3):295-309. doi: 10.1007/s10545-007-0455-8. Epub 2007 May 19.
Pubmed: 17520339
Stoychev G, Kierdaszuk B, Shugar D: Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems. Eur J Biochem. 2002 Aug;269(16):4048-57. doi: 10.1046/j.1432-1033.2002.03097.x.
Pubmed: 12180982
Vogels GD, Van der Drift C: Degradation of purines and pyrimidines by microorganisms. Bacteriol Rev. 1976 Jun;40(2):403-68. doi: 10.1128/br.40.2.403-468.1976.
Pubmed: 786256
Xi H, Schneider BL, Reitzer L: Purine catabolism in Escherichia coli and function of xanthine dehydrogenase in purine salvage. J Bacteriol. 2000 Oct;182(19):5332-41. doi: 10.1128/JB.182.19.5332-5341.2000.
Pubmed: 10986234
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