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Pathway Description
Purine Metabolism
Bos taurus
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
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
Pubmed: 16305752
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Pubmed: 19390049
Gaidarov IO, Suslov ON, Ovchinnikova TV, Abdulaev NG: [Guanylate kinase from bovine retina: isolation, primary structure, and expression in E. coli]. Bioorg Khim. 1994 Apr;20(4):367-81.
Pubmed: 7911663
Gaidarov IO, Suslov ON, Abdulaev NG: Enzymes of the cyclic GMP metabolism in bovine retina. I. Cloning and expression of the gene for guanylate kinase. FEBS Lett. 1993 Nov 29;335(1):81-4. doi: 10.1016/0014-5793(93)80444-y.
Pubmed: 8243671
Allegrini S, Pesi R, Tozzi MG, Fiol CJ, Johnson RB, Eriksson S: Bovine cytosolic IMP/GMP-specific 5'-nucleotidase: cloning and expression of active enzyme in Escherichia coli. Biochem J. 1997 Dec 1;328 ( Pt 2):483-7. doi: 10.1042/bj3280483.
Pubmed: 9371705
Bzowska A, Luic M, Schroder W, Shugar D, Saenger W, Koellner G: Calf spleen purine nucleoside phosphorylase: purification, sequence and crystal structure of its complex with an N(7)-acycloguanosine inhibitor. FEBS Lett. 1995 Jul 3;367(3):214-8. doi: 10.1016/0014-5793(95)00540-p.
Pubmed: 7607309
Koellner G, Luic M, Shugar D, Saenger W, Bzowska A: Crystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 A resolution. J Mol Biol. 1997 Jan 17;265(2):202-16. doi: 10.1006/jmbi.1996.0730.
Pubmed: 9020983
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
Wohlke A, Drogemuller C, Kuiper H, Leeb T, Distl O: Molecular characterization and chromosomal assignment of the bovine glycinamide ribonucleotide formyltransferase (GART) gene on cattle chromosome 1q12.1-q12.2. Gene. 2005 Mar 28;348:73-81. doi: 10.1016/j.gene.2004.12.038.
Pubmed: 15777723
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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