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Pathway Description
Purine Nucleotides De Novo Biosynthesis
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2016-02-22
Last Updated: 2019-08-14
The biosynthesis of purine nucleotides is a complex process that begins with a phosphoribosyl pyrophosphate. This compound interacts with water and L-glutamine through a amidophosphoribosyl transferase resulting in a pyrophosphate, L-glutamic acid and a 5-phosphoribosylamine. The latter compound proceeds to interact with a glycine through an ATP driven phosphoribosylamine-glycine ligase resulting in the addition of glycine to the compound. This reaction releases an ADP, a phosphate, a hydrogen ion and a N1-(5-phospho-β-D-ribosyl)glycinamide. The latter compound interacts with formic acid, through an ATP driven phosphoribosylglycinamide formyltransferase 2 resulting in a phosphate, an ADP, a hydrogen ion and a 5-phosphoribosyl-N-formylglycinamide. The latter compound interacts with L-glutamine, and water through an ATP-driven phosphoribosylformylglycinamide synthetase resulting in a release of a phosphate, an ADP, a hydrogen ion, a L-glutamic acid and a 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine. The latter compound interacts with an ATP driven phosphoribosylformylglycinamide cyclo-ligase resulting in a release of ADP, a phosphate, a hydrogen ion and a 5-aminoimidazole ribonucleotide. The latter compound interacts with a hydrogen carbonate through an ATP driven N5-carboxyaminoimidazole ribonucleotide synthetase resulting in a release of a phosphate, an ADP, a hydrogen ion and a N5-carboxyaminoimidazole ribonucleotide.The latter compound then interacts with a N5-carboxyaminoimidazole ribonucleotide mutase resulting in a 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate. This compound interacts with an L-aspartic acid through an ATP driven phosphoribosylaminoimidazole-succinocarboxamide synthase resulting in a phosphate, an ADP, a hydrogen ion and a SAICAR. SAICAR interacts with an adenylosuccinate lyase resulting in a fumaric acid and an AICAR. AICAR interacts with a formyltetrahydrofolate through a AICAR transformylase / IMP cyclohydrolase resulting in a release of a tetrahydropterol mono-l-glutamate and a FAICAR. The latter compound, FAICAR, interacts in a reversible reaction through a AICAR transformylase / IMP cyclohydrolase resulting in a release of water and Inosinic acid. Inosinic acid can be metabolized to produce dGTP and dATP three different methods each. dGTP: Inosinic acid, water and NAD are processed by IMP dehydrogenase resulting in a release of NADH, a hydrogen ion and Xanthylic acid. Xanthylic acid interacts with L-glutamine, and water through an ATP driven GMP synthetase resulting in pyrophosphate, AMP, L-glutamic acid, a hydrogen ion and Guanosine monophosphate. The latter compound is the phosphorylated by reacting with an ATP driven guanylate kinase resulting in a release of ADP and a Gaunosine diphosphate. Guanosine diphosphate can be metabolized in three different ways: 1.-Guanosine diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and a Guanosine triphosphate. This compound interacts with a reduced flavodoxin protein through a ribonucleoside-triphosphate reductase resulting in a oxidized flavodoxin a water moleculer and a dGTP 2.-Guanosine diphosphate interacts with a reduced NrdH glutaredoxin-like proteins through a ribonucleoside-diphosphate reductase 2 resulting in the release of an oxidized NrdH glutaredoxin-like protein, a water molecule and a dGDP. The dGDP is then phosphorylated by interacting with an ATP-driven nucleoside diphosphate kinase resulting in an ADP and dGTP. 3.-Guanosine diphosphate interacts with a reduced thioredoxin ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dGDP. The dGDP is then phosphorylated by interacting with an ATP-driven nucleoside diphosphate kinase resulting in an ADP and dGTP. dATP: Inosinic acid interacts with L-aspartic acid through an GTP driven adenylosuccinate synthase results in the release of GDP, a hydrogen ion, a phosphate and N(6)-(1,2-dicarboxyethyl)AMP. The latter compound is then cleaved by a adenylosuccinate lyase resulting in a fumaric acid and an Adenosine monophosphate. This compound is then phosphorylated by an adenylate kinase resulting in the release of ATP and an adenosine diphosphate. Adenosine diphosphate can be metabolized in three different ways: 1.-Adenosine diphosphate is involved in a reversible reaction by interacting with a hydrogen ion and a phosphate through a ATP synthase / thiamin triphosphate synthase resulting in a hydrogen ion, a water molecule and an Adenosine triphosphate. The adenosine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in an oxidized flavodoxin, a water molecule and a dATP 2.- Adenosine diphosphate interacts with an reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, a oxidized thioredoxin and a dADP. The dADP is then phosphorylated by a nucleoside diphosphate kinase resulting in the release of ADP and a dATP 3.- Adenosine diphosphate interacts with an reduced NrdH glutaredoxin-like protein through a ribonucleoside diphosphate reductase 2 resulting in a release of a water molecule, a oxidized glutaredoxin-like protein and a dADP. The dADP is then phosphorylated by a nucleoside diphosphate kinase resulting in the release of ADP and a dATP
References
Purine Nucleotides De Novo Biosynthesis References
Rolfes RJ: Regulation of purine nucleotide biosynthesis: in yeast and beyond. Biochem Soc Trans. 2006 Nov;34(Pt 5):786-90. doi: 10.1042/BST0340786.
Pubmed: 17052198
Wang L, Westberg J, Bolske G, Eriksson S: Novel deoxynucleoside-phosphorylating enzymes in mycoplasmas: evidence for efficient utilization of deoxynucleosides. Mol Microbiol. 2001 Nov;42(4):1065-73.
Pubmed: 11737647
Zalkin H, Dixon JE: De novo purine nucleotide biosynthesis. Prog Nucleic Acid Res Mol Biol. 1992;42:259-87.
Pubmed: 1574589
Bussey H, Kaback DB, Zhong W, Vo DT, Clark MW, Fortin N, Hall J, Ouellette BF, Keng T, Barton AB, et al.: The nucleotide sequence of chromosome I from Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3809-13. doi: 10.1073/pnas.92.9.3809.
Pubmed: 7731988
Engel SR, Dietrich FS, Fisk DG, Binkley G, Balakrishnan R, Costanzo MC, Dwight SS, Hitz BC, Karra K, Nash RS, Weng S, Wong ED, Lloyd P, Skrzypek MS, Miyasato SR, Simison M, Cherry JM: The reference genome sequence of Saccharomyces cerevisiae: then and now. G3 (Bethesda). 2014 Mar 20;4(3):389-98. doi: 10.1534/g3.113.008995.
Pubmed: 24374639
Hyle JW, Shaw RJ, Reines D: Functional distinctions between IMP dehydrogenase genes in providing mycophenolate resistance and guanine prototrophy to yeast. J Biol Chem. 2003 Aug 1;278(31):28470-8. doi: 10.1074/jbc.M303736200. Epub 2003 May 13.
Pubmed: 12746440
Berger A, Schiltz E, Schulz GE: Guanylate kinase from Saccharomyces cerevisiae. Isolation and characterization, crystallization and preliminary X-ray analysis, amino acid sequence and comparison with adenylate kinases. Eur J Biochem. 1989 Sep 15;184(2):433-43. doi: 10.1111/j.1432-1033.1989.tb15035.x.
Pubmed: 2551688
Konrad M: Cloning and expression of the essential gene for guanylate kinase from yeast. J Biol Chem. 1992 Dec 25;267(36):25652-5.
Pubmed: 1334480
Jacq C, Alt-Morbe J, Andre B, Arnold W, Bahr A, Ballesta JP, Bargues M, Baron L, Becker A, Biteau N, Blocker H, Blugeon C, Boskovic J, Brandt P, Bruckner M, Buitrago MJ, Coster F, Delaveau T, del Rey F, Dujon B, Eide LG, Garcia-Cantalejo JM, Goffeau A, Gomez-Peris A, Zaccaria P, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome IV. Nature. 1997 May 29;387(6632 Suppl):75-8.
Pubmed: 9169867
Takeda M, Vassarotti A, Douglas MG: Nuclear genes coding the yeast mitochondrial adenosine triphosphatase complex. Primary sequence analysis of ATP2 encoding the F1-ATPase beta-subunit precursor. J Biol Chem. 1985 Dec 15;260(29):15458-65.
Pubmed: 2866186
Liang Y, Ackerman SH: Characterization of mutations in the beta subunit of the mitochondrial F1-ATPase that produce defects in enzyme catalysis and assembly. J Biol Chem. 1996 Oct 25;271(43):26522-8. doi: 10.1074/jbc.271.43.26522.
Pubmed: 8900121
Galibert F, Alexandraki D, Baur A, Boles E, Chalwatzis N, Chuat JC, Coster F, Cziepluch C, De Haan M, Domdey H, Durand P, Entian KD, Gatius M, Goffeau A, Grivell LA, Hennemann A, Herbert CJ, Heumann K, Hilger F, Hollenberg CP, Huang ME, Jacq C, Jauniaux JC, Katsoulou C, Karpfinger-Hartl L, et al.: Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X. EMBO J. 1996 May 1;15(9):2031-49.
Pubmed: 8641269
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