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Pathway Description
Purine Metabolism
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-15
Purine is a water soluble, organic compound. Purines, including purines that have been substituted, are the most widely distributed kind of nitrogen-containing heterocycle in nature. The two most important purines are adenine and guanine. Other notable examples are hypoxanthine, xanthine, theobromine, caffeine, uric acid and isoguanine. This pathway depicts a number of processes including purine nucleotide biosynthesis, purine degradation and purine salvage. The main organ where purine nucleotides are created is the liver. This process starts as
5-phospho-α-ribosyl-1-pyrophosphate, or PRPP, and creates inosine 5’-monophosphate, or IMP. Following a series of reactions, PRPP uses compounds such as tetrahydrofolate derivatives, glycine and ATP, and IMP is produced as a result. Glutamine PRPP amidotransferase catalyzes PRPP into 5-phosphoribosylamine, or PRA. 5-phosphoribosylamine is converted to glycinamide ribotide (GAR) then to formyglycinamide ribotide (FGAR). This set of reactions is catalyzed by a trifunctional enzyme containing GAR synthetase, GAR transformylase and AIR synthetase. FGAR is converted to formylglycinamidine-ribonucleotide (FGAM) by formylglycinamide synthase. FGAM is then converted by aminoimidzaole ribotide synthase to 5-aminoimidazole ribotide (AIR) then carboxylated by aminoimidazole ribotide carboxylase to carboxyaminoimidazole ribotide (CAIR). CAIR is then converted tosuccinylaminoimidazole carboxamide ribotide (SAICAR) by succinylaminoimidazole carboxamide ribotide synthase followed by conversion to AICAR (via adenylsuccinate lyase) then to FAICAR (via aminoimidazole carboxamide ribotide transformylase). FAICAR is finally converted to inosine monophosphate (IMP) by IMP cyclohydrolase. Because of the complexity of this synthetic process, the purine ring is actually composed of atoms derived from many different molecules. The N1 atom arises from the amine group of Asp, the C2 and C8 atoms originate from formate, the N3 and N9 atoms come from the amide group of Gln, the C4, C5 and N7 atoms come from Gly and the C6 atom comes from CO2. IMP creates a fork in the road for the creation of purine, as it can either become GMP or AMP. AMP is generated from IMP via adenylsuccinate synthetase (which adds aspartate) and adenylsuccinate lyase. GMP is generated via the action of IMP dehydrogenase and GMP synthase. Purine nucleotides being catabolized creates uric acid. Beginning from AMP, the enzymes AMP deaminase and nucleotidase work in concert to generate inosine. Alternately, AMP may be dephosphorylate by nucleotidase and then adenosine deaminase (ADA) converts the free adenosine to inosine. The enzyme purine nucleotide phosphorylase (PNP) converts inosine to hypoxanthine, while xanthine oxidase converts hypoxanthine to xanthine and finally to uric acid. GMP and XMP can also be converted to uric acid via the action of nucleotidase, PNP, guanine deaminase and xanthine oxidase. Nucleotide creation stemming from the purine bases and purine nucleosides happens in steps that are called the “salvage pathways”. The free purine bases phosphoribosylated and reconverted to their respective nucleotides.
References
Purine Metabolism References
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Mehus JG, Deloukas P, Lambeth DO: NME6: a new member of the nm23/nucleoside diphosphate kinase gene family located on human chromosome 3p21.3. Hum Genet. 1999 Jun;104(6):454-9. doi: 10.1007/s004390050987.
Pubmed: 10453732
Fausther M, Lecka J, Kukulski F, Levesque SA, Pelletier J, Zimmermann H, Dranoff JA, Sevigny J: Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G785-95. doi: 10.1152/ajpgi.00293.2006. Epub 2006 Nov 9.
Pubmed: 17095758
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
Ahmed F, Torrado M, Zinovieva RD, Senatorov VV, Wistow G, Tomarev SI: Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis. Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3081-90. doi: 10.1167/iovs.04-0302.
Pubmed: 15326124
Stegmann AP, Honders MW, Willemze R, Landegent JE: Cloning of the Dck gene encoding rat deoxycytidine kinase. Gene. 1994 Dec 15;150(2):351-4. doi: 10.1016/0378-1119(94)90451-0.
Pubmed: 7821805
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Fieldhouse D, Golding GB: The rat adenine phosphoribosyltransferase sequence shows evolutionary rate variation among exons in rodents. Genome. 1993 Dec;36(6):1107-10.
Pubmed: 8112572
Maurya DK, Sundaram CS, Bhargava P: Proteome profile of the mature rat olfactory bulb. Proteomics. 2009 May;9(9):2593-9. doi: 10.1002/pmic.200800664.
Pubmed: 19343716
Chiaverotti TA, Battula N, Monnat RJ Jr: Rat hypoxanthine phosphoribosyltransferase cDNA cloning and sequence analysis. Genomics. 1991 Dec;11(4):1158-60.
Pubmed: 1783384
Chiaverotti TA, Battula N, Monnat RJ Jr: Rat hypoxanthine phosphoribosyltransferase cDNA cloning and sequence analysis. Adv Exp Med Biol. 1991;309B:117-20. doi: 10.1007/978-1-4615-7703-4_26.
Pubmed: 1781355
Jansen JG, Vrieling H, van Zeeland AA, Mohn GR: The gene encoding hypoxanthine-guanine phosphoribosyltransferase as target for mutational analysis: PCR cloning and sequencing of the cDNA from the rat. Mutat Res. 1992 Apr;266(2):105-16. doi: 10.1016/0027-5107(92)90178-5.
Pubmed: 1373820
Taira M, Ishijima S, Kita K, Yamada K, Iizasa T, Tatibana M: Nucleotide and deduced amino acid sequences of two distinct cDNAs for rat phosphoribosylpyrophosphate synthetase. J Biol Chem. 1987 Nov 5;262(31):14867-70.
Pubmed: 2822704
Ishijima S, Taira M, Tatibana M: Complete cDNA sequence of rat phosphoribosylpyrophosphate synthetase subunit I (PRS I). Nucleic Acids Res. 1989 Nov 11;17(21):8860. doi: 10.1093/nar/17.21.8860.
Pubmed: 2555779
Shimada H, Taira M, Yamada K, Iizasa T, Tatibana M: Structure of the rat PRPS1 gene encoding phosphoribosylpyrophosphate synthetase subunit I. J Biol Chem. 1990 Mar 5;265(7):3956-60.
Pubmed: 2154494
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000050
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