If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Purine Nucleotide Biosynthesis → Purine Nucleotide Salvage → Guanine and Guanosine Salvage|
Guanosine nucleotides can be synthesized de novo as shown in pathway superpathway of guanosine nucleotides de novo biosynthesis II. In that route GMP is synthesized via IMP and XMP, which is converted to GMP by the action of GMP synthetase, an enzyme that can use either glutamine or ammonia as substrate. Note that the free base guanine or the ribonucleoside guanosine are not produced via the de novo biosynthesis pathway.
Many organisms can also recycle guanosine nucleotides by a combination of degradation and salvage pathways. The degradation pathway is responsible for degradation of the nucleotides to the nucleoside guanosine and the base guanine, which can be further degraded via xanthine and urate (see pathway guanosine nucleotides degradation III). In some organisms urate is catabolized to basic building blocks (see MetaCyc pathway urate degradation to allantoin I). However, both guanosine and guanine can be salvaged by certain enzymes and converted back to their nucleotide form as shown in this pathway and pathway guanine and guanosine salvage III. In Escherichia coli the pathway shown here is the major salvage route.
About This Pathway
In E. coli phosphorolytic cleavage of the N-glycosyl bond of of purine ribonucleosides or deoxyribonucleosides, as shown here for guanosine, is catalyzed by the purine nucleoside phosphorylases encoded by genes deoD and xapA. The released purine base, in this case guanine, is subsequently converted to a nucleotide, in this case GMP, by the action of phosphoribosyltransferases encoded by genes gpt and hpt.
DeoD is the classical purine nucleoside phosphorylase I. It utilizes guanosine, adenosine, or inosine (or their corresponding deoxyribonucleosides) as substrate. Synthesis of this enzyme is induced in the presence of deoxyribonucleosides, inosine, or guanosine in the growth medium. As shown here it cleaves guanosine to guanine and α-D-ribose-1-phosphate. XapA (xanthosine phosphorylase) cleaves 6-oxopurine ribonucleosides and deoxyribonucleosides and is induced after exposure of cells to xanthosine in the medium [HammerJespersen80].
In the second step, the two phosphoribosyltransferases Hpt and Gpt salvage 6-oxopurine bases. Gpt and Hpt utilize 5-phospho-α-D-ribose 1-diphosphate to convert the free base guanine to the mononucleotide GMP. As shown in Salmonella typhimurium, together these enzymes can rescue all 6-oxopurine bases [Gots72].
Review: Jensen, K.F., G. Dandanell, B. Hove-Jensen and M. Willemoes (2008) "Nucleotides, Nucleosides and Nucleobases" EcoSal 3.6.2 [ECOSAL]
Superpathways: superpathway of guanine and guanosine salvage
Variants: guanine and guanosine salvage III
Gots72: Gots JS, Benson CE, Shumas SR (1972). "Genetic separation of hypoxanthine and guanine-xanthine phosphoribosyltransferase activities by deletion mutations in Salmonella typhimurium." J Bacteriol 112(2);910-6. PMID: 4563984
HammerJespersen80: Hammer-Jespersen K, Buxton RS, Hansen TD (1980). "A second purine nucleoside phosphorylase in Escherichia coli K-12. II. Properties of xanthosine phosphorylase and its induction by xanthosine." Mol Gen Genet 1980;179(2);341-8. PMID: 7007809
Bennett03: Bennett EM, Li C, Allan PW, Parker WB, Ealick SE (2003). "Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase." J Biol Chem 278(47);47110-8. PMID: 12937174
Bennett03a: Bennett EM, Anand R, Allan PW, Hassan AE, Hong JS, Levasseur DN, McPherson DT, Parker WB, Secrist JA, Sorscher EJ, Townes TM, Waud WR, Ealick SE (2003). "Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system." Chem Biol 10(12);1173-81. PMID: 14700625
Bertoša14: Bertoša B, Mikleušević G, Wielgus-Kutrowska B, Narczyk M, Hajnic M, Leščić Ašler I, Tomic S, Luic M, Bzowska A (2014). "Homooligomerization is needed for stability: a molecular modelling and solution study of Escherichia coli purine nucleoside phosphorylase." FEBS J 281(7);1860-71. PMID: 24785777
Bezirdzhian86: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1986). "[Isolation of the hexameric form of purine nucleoside phosphorylase from E. coli. Comparative study of trimeric and hexameric forms of the enzyme]." Biokhimiia 1986;51(7);1085-92. PMID: 3089333
Bezirdzhian87: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1987). "[Hexamere purine nucleoside phosphorylase from Escherichia coli K-12. Kinetic analysis and mechanism of reaction]." Biokhimiia 52(11);1770-6. PMID: 3125860
Bezirdzhian87a: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1987). "[Hexameric purine nucleoside phosphorylase II from Escherichia coli K-12. Physico-chemical and catalytic properties and stabilization with substrates]." Biokhimiia 1987;52(10);1624-31. PMID: 3122852
Buxton75: Buxton RS (1975). "Genetic analysis of thymidine-resistant and low-thymine-requiring mutants of Escherichia coli K-12 induced by bacteriophage Mu-1." J Bacteriol 121(2);475-84. PMID: 1089630
Buxton80: Buxton RS, Hammer-Jespersen K, Valentin-Hansen P (1980). "A second purine nucleoside phosphorylase in Escherichia coli K-12. I. Xanthosine phosphorylase regulatory mutants isolated as secondary-site revertants of a deoD mutant." Mol Gen Genet 179(2);331-40. PMID: 7007808
Bzowska88: Bzowska A, Kulikowska E, Darzynkiewicz E, Shugar D (1988). "Purine nucleoside phosphorylase. Structure-activity relationships for substrate and inhibitor properties of N-1-, N-7-, and C-8-substituted analogues; differentiation of mammalian and bacterial enzymes with N-1-methylinosine and guanosine." J Biol Chem 263(19);9212-7. PMID: 3132457
Dandanell05: Dandanell G, Szczepanowski RH, Kierdaszuk B, Shugar D, Bochtler M (2005). "Escherichia coli purine nucleoside phosphorylase II, the product of the xapA gene." J Mol Biol 348(1);113-25. PMID: 15808857
Deo85: Deo SS, Tseng WC, Saini R, Coles RS, Athwal RS (1985). "Purification and characterization of Escherichia coli xanthine-guanine phosphoribosyltransferase produced by plasmid pSV2gpt." Biochim Biophys Acta 839(3);233-9. PMID: 3886014
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Ding10: Ding QB, Ou L, Wei DZ, Wei XK, Xu YM, Zhang CY (2010). "Enzymatic synthesis of nucleosides by nucleoside phosphorylase co-expressed in Escherichia coli." J Zhejiang Univ Sci B 11(11);880-8. PMID: 21043057
Dong14: Dong WR, Sun CC, Zhu G, Hu SH, Xiang LX, Shao JZ (2014). "New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD(+) salvage from nicotinamide." BMC Microbiol 14;29. PMID: 24506841
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