2.02012-05-31 10:25:26 -06002015-06-03 15:53:26 -0600ECMDB00280M2MDB000115Phosphoribosyl pyrophosphatePhosphoribosyl pyrophosphate (PRPP) is a pentosephosphate. The key substance in the biosynthesis of histidine, tryptophan, and purine and pyrimidine nucleotides. It is formed from ribose 5-phosphate by the enzyme ribose-phosphate diphosphokinase. It plays a role in transferring phosphate groups in several reactions. (Wikipedia)α-D-5-P-RibosylPPα-D-5-phosphoribosylPP5-phospho-a-D-Ribose 1-diphosphate5-phospho-a-D-Ribose 1-diphosphoric acid5-Phospho-a-D-ribose-1-diphosphate5-phospho-a-D-Ribose-1-diphosphoric acid5-Phospho-a-D-ribosyl pyrophosphate5-phospho-a-D-Ribosyl pyrophosphoric acid5-phospho-a-D-Riobse 1-diphosphate5-phospho-a-D-Riobse 1-diphosphoric acid5-phospho-a-delta-Ribose 1-diphosphate5-phospho-a-delta-Ribose 1-diphosphoric acid5-phospho-a-delta-Ribose-1-diphosphate5-phospho-a-delta-Ribose-1-diphosphoric acid5-phospho-a-delta-Ribosyl pyrophosphate5-phospho-a-delta-Ribosyl pyrophosphoric acid5-phospho-a-δ-Ribose 1-diphosphate5-phospho-a-δ-Ribose 1-diphosphoric acid5-phospho-a-δ-Ribose-1-diphosphate5-phospho-a-δ-Ribose-1-diphosphoric acid5-phospho-a-δ-Ribosyl pyrophosphate5-phospho-a-δ-Ribosyl pyrophosphoric acid5-Phospho-alpha-D-ribose 1-diphosphate5-phospho-alpha-D-Ribose 1-diphosphoric acid5-Phospho-alpha-D-ribose-1-diphosphate5-phospho-alpha-D-Ribose-1-diphosphoric acid5-Phospho-alpha-D-ribosyl pyrophosphate5-phospho-alpha-D-Ribosyl pyrophosphoric acid5-Phospho-alpha-D-riobse 1-diphosphate5-phospho-alpha-D-Riobse 1-diphosphoric acid5-Phospho-alpha-delta-ribose 1-diphosphate5-phospho-alpha-delta-Ribose 1-diphosphoric acid5-Phospho-alpha-delta-ribose-1-diphosphate5-phospho-alpha-delta-Ribose-1-diphosphoric acid5-Phospho-alpha-delta-ribosyl pyrophosphate5-phospho-alpha-delta-Ribosyl pyrophosphoric acid5-Phospho-ribosyl-pyrophosphate5-phospho-Ribosyl-pyrophosphoric acid5-phospho-α-D-Ribose 1-diphosphate5-phospho-α-D-Ribose 1-diphosphoric acid5-phospho-α-D-Ribose-1-diphosphate5-phospho-α-D-Ribose-1-diphosphoric acid5-phospho-α-D-Ribosyl pyrophosphate5-phospho-α-D-Ribosyl pyrophosphoric acid5-phospho-α-D-Riobse 1-diphosphate5-phospho-α-D-Riobse 1-diphosphoric acid5-phospho-α-δ-Ribose 1-diphosphate5-phospho-α-δ-Ribose 1-diphosphoric acid5-phospho-α-δ-Ribose-1-diphosphate5-phospho-α-δ-Ribose-1-diphosphoric acid5-phospho-α-δ-Ribosyl pyrophosphate5-phospho-α-δ-Ribosyl pyrophosphoric acid5-Phosphoribose 1-pyrophosphate5-Phosphoribose 1-pyrophosphoric acid5-Phosphoribosyl 1-diphosphate5-Phosphoribosyl 1-diphosphoric acid5-Phosphoribosyl 1-pyrophosphate5-Phosphoribosyl 1-pyrophosphoric acid5-Phosphoribosyl a-1-pyrophosphate5-Phosphoribosyl a-1-pyrophosphoric acid5-Phosphoribosyl diphosphate5-Phosphoribosyl diphosphoric acid5-Phosphoribosyl-1-PP5-Phosphoribosyl-1-pyrophosphate5-Phosphoribosyl-1-pyrophosphoric acid5-Phosphoribosyl-PP5-Phosphoribosylpyrophosphate5-Phosphoribosylpyrophosphoric acid5-Phosphorylribose 1-a-diphosphate5-Phosphorylribose 1-a-diphosphoric acid5-Phosphorylribose 1-alpha-diphosphate5-Phosphorylribose 1-alpha-diphosphoric acid5-Phosphorylribose 1-pyrophosphate5-Phosphorylribose 1-pyrophosphoric acid5-Phosphorylribose 1-α-diphosphate5-Phosphorylribose 1-α-diphosphoric acid5-Phosphorylribosyl 1-pyrophosphate5-Phosphorylribosyl 1-pyrophosphoric acidA-D-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) Ribofuranosea-D-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranosea-D-5-P-RibosylPPA-D-5-Phosphoribosyl 1-pyrophosphatea-D-5-Phosphoribosyl 1-pyrophosphoric acida-D-5-PhosphoribosylPPA-D-Ribofuranose 5-phosphate 1-pyrophosphatea-D-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidA-D-Ribofuranose, 5-(dihydrogen phosphate) 1-(trihydrogen diphosphate)a-D-Ribofuranose, 5-(dihydrogen phosphoric acid) 1-(trihydrogen diphosphoric acid)a-delta-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) ribofuranosea-delta-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranosea-delta-5-Phosphoribosyl 1-pyrophosphatea-delta-5-Phosphoribosyl 1-pyrophosphoric acida-delta-Ribofuranose 5-phosphate 1-pyrophosphatea-delta-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acida-δ-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) ribofuranosea-δ-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranosea-δ-5-Phosphoribosyl 1-pyrophosphatea-δ-5-Phosphoribosyl 1-pyrophosphoric acida-δ-Ribofuranose 5-phosphate 1-pyrophosphatea-δ-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidAlpha-D-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) Ribofuranosealpha-D-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranoseAlpha-D-5-P-RibosylPPAlpha-D-5-Phosphoribosyl 1-pyrophosphatealpha-D-5-Phosphoribosyl 1-pyrophosphoric acidAlpha-D-5-PhosphoribosylPPAlpha-D-Ribofuranose 5-phosphate 1-pyrophosphatealpha-D-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidAlpha-D-Ribofuranose, 5-(dihydrogen phosphate) 1-(trihydrogen diphosphate)alpha-D-Ribofuranose, 5-(dihydrogen phosphoric acid) 1-(trihydrogen diphosphoric acid)Alpha-delta-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) Ribofuranosealpha-delta-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranoseAlpha-delta-5-Phosphoribosyl 1-pyrophosphatealpha-delta-5-Phosphoribosyl 1-pyrophosphoric acidAlpha-delta-Ribofuranose 5-phosphate 1-pyrophosphatealpha-delta-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidPhosphoribosyl pyrophosphatePhosphoribosyl pyrophosphoric acidPhosphoribosyl-1-pyrophosphatePhosphoribosyl-1-pyrophosphoric acidPhosphoribosyl-pyrophosphatePhosphoribosyl-pyrophosphoric acidPhosphoribosylpyrophosphatePhosphoribosylpyrophosphoratePhosphoribosylpyrophosphoric acidPP-Ribose-PPRib-PPPRPPα-D-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) ribofuranoseα-D-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranoseα-D-5-P-RibosylPPα-D-5-Phosphoribosyl 1-pyrophosphateα-D-5-Phosphoribosyl 1-pyrophosphoric acidα-D-5-PhosphoribosylPPα-D-Ribofuranose 5-phosphate 1-pyrophosphateα-D-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidα-D-Ribofuranose, 5-(dihydrogen phosphate) 1-(trihydrogen diphosphate)α-D-Ribofuranose, 5-(dihydrogen phosphoric acid) 1-(trihydrogen diphosphoric acid)α-δ-5-(Dihydrogen phosphate) 1-(trihydrogen pyrophosphate) ribofuranoseα-δ-5-(Dihydrogen phosphoric acid) 1-(trihydrogen pyrophosphoric acid) ribofuranoseα-δ-5-Phosphoribosyl 1-pyrophosphateα-δ-5-Phosphoribosyl 1-pyrophosphoric acidα-δ-Ribofuranose 5-phosphate 1-pyrophosphateα-δ-Ribofuranose 5-phosphoric acid 1-pyrophosphoric acidC5H13O14P3390.0696389.95181466[({[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(phosphonooxy)methyl]oxolan-2-yl]oxy}(hydroxy)phosphoryl)oxy]phosphonic acidphosphoribosylpyrophosphate7540-64-9O[C@H]1[C@@H](O)[C@@H](O[P@](O)(=O)OP(O)(O)=O)O[C@@H]1COP(O)(O)=OInChI=1S/C5H13O14P3/c6-3-2(1-16-20(8,9)10)17-5(4(3)7)18-22(14,15)19-21(11,12)13/h2-7H,1H2,(H,14,15)(H2,8,9,10)(H2,11,12,13)/t2-,3-,4-,5-/m1/s1PQGCEDQWHSBAJP-TXICZTDVSA-NSolidCytosollogp-0.74logs-1.53solubility1.16e+01 g/llogp-3pka_strongest_acidic1.09pka_strongest_basic-3.7iupac[({[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(phosphonooxy)methyl]oxolan-2-yl]oxy}(hydroxy)phosphoryl)oxy]phosphonic acidaverage_mass390.0696mono_mass389.95181466smilesO[C@H]1[C@@H](O)[C@@H](O[P@](O)(=O)OP(O)(O)=O)O[C@@H]1COP(O)(O)=OformulaC5H13O14P3inchiInChI=1S/C5H13O14P3/c6-3-2(1-16-20(8,9)10)17-5(4(3)7)18-22(14,15)19-21(11,12)13/h2-7H,1H2,(H,14,15)(H2,8,9,10)(H2,11,12,13)/t2-,3-,4-,5-/m1/s1inchikeyPQGCEDQWHSBAJP-TXICZTDVSA-Npolar_surface_area229.74refractivity62.58polarizability27.46rotatable_bond_count7acceptor_count11donor_count7physiological_charge-4formal_charge0Pentose phosphate pathwayec00030Alanine, aspartate and glutamate metabolismec00250Purine metabolismec00230Pyrimidine metabolismThe metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate.
Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate.
1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate.
2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate.
3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate
4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate.PW000942ec00240MetabolicPhenylalanine, tyrosine and tryptophan biosynthesisec00400Tryptophan metabolismThe biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan.
The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA
PW000815ec00380MetabolicDrug metabolism - other enzymesec00983Histidine metabolismec00340Nicotinate and nicotinamide metabolismec00760Microbial metabolism in diverse environmentsec01120Metabolic pathwayseco01100NAD biosynthesisNicotinamide adenine dinucleotide (NAD) can be biosynthesized from L-aspartic acid.This amino acid reacts with oxygen through an L-aspartate oxidase resulting in a hydrogen ion, hydrogen peroxide and an iminoaspartic acid. The latter compound interacts with dihydroxyacetone phosphate through a quinolinate synthase A, resulting in a phosphate, water, and a quinolic acid. Quinolic acid interacts with phosphoribosyl pyrophosphate and hydrogen ion through a quinolinate phosphoribosyltransferase resulting in pyrophosphate, carbon dioxide and nicotinate beta-D-ribonucleotide. This last compound is adenylated through an ATP driven nicotinate-mononucleotide adenylyltransferase releasing a pyrophosphate and resulting in a nicotinic acid adenine dinucleotide.
Nicotinic acid adenine dinucleotide is processed through an NAD synthetase, NH3-dependent in two different manners.
In the first case, Nicotinic acid adenine dinucleotide interacts with ATP, L-glutamine and water through the enzyme and results in hydrogen ion, AMP, pyrophosphate, L-glutamic acid and NAD.
In the second case, Nicotinic acid adenine dinucleotide interacts with ATP and ammonium through the enzyme resulting in a pyrophosphate, AMP, hydrogen ion and NAD.
NAD then proceeds to regulate its own pathway by repressing L-aspartate oxidase.
As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate , while in eukaryotes, the de novo pathway starts with tryptophan.
PW000829MetabolicNAD salvageEven though NAD molecules are not consumed during oxidation reactions, they have a relatively short half-life. For example, in E. coli the NAD+ half-life is 90 minutes. Once enzymatically degraded, the pyrimidine moiety of the molecule can be recouped via the NAD salvage cycles. This pathway is used for two purposes: it recycles the internally degraded NAD products nicotinamide D-ribonucleotide (also known as nicotinamide mononucleotide, or NMN) and nicotinamide, and it is used for the assimilation of exogenous NAD+.
NAD reacts spontaneously with water resulting in the release of hydrogen ion, AMP and beta-nicotinamide D-ribonucleotide. This enzyme can either interact spontaneously with water resulting in the release of D-ribofuranose 5-phosphate, hydrogen ion and Nacinamide. On the other hand beta-nicotinamide D-ribonucleotide can also react with water through NMN amidohydrolase resulting in ammonium, and Nicotinate beta-D-ribonucleotide. Also it can interact with water spontaneously resulting in the release of phosphate resulting in a Nicotinamide riboside.
Niacinamide interacts with water through a nicotinamidase resulting in a release of ammonium and nicotinic acid. This compound interacts with water and phosphoribosyl pyrophosphate through an ATP driven nicotinate phosphoribosyltransferase resulting in the release of ADP, pyrophosphate and phosphate and nicotinate beta-D-ribonucleotide.
Nicotinamide riboside interacts with an ATP driven NadR DNA-binding transcriptional repressor and NMN adenylyltransferase (Escherichia coli) resulting in a ADP, hydrogen ion and beta-nicotinamide D-ribonucleotide. This compound interacts with ATP and hydrogen ion through NadR DNA-binding transcriptional repressor and NMN adenylyltransferase resulting in pyrophosphate and NAD.
Nicotinate beta-D-ribonucleotide is adenylated through the interaction with ATP and a hydrogen ion through a nicotinate-mononucleotide adenylyltransferase resulting in pyrophosphate and Nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide interacts with L-glutamine and water through an ATP driven NAD synthetase, NH3-dependent resulting in AMP, pyrophosphate, hydrogen ion, L-glutamic acid and NAD.
PW000830MetabolicPRPP BiosynthesisThe biosynthesis of phosphoribosyl pyrophosphate begins with a product of the pentose phosphate, D-ribose 5-phosphate interact with a phosphopentomutase resulting in a Ribose 1-phosphate or it can be phosphorylated through an ATP driven ribose-phosphate diphosphokinase resulting in a release of a hydrogen ion, an AMP and a phosphoribosyl pyrophosphate. The latter compound is then involved in the purine nucleotides de novo biosynthesis pathway.
Ribose 1-phosphate can interact spontaneously with ATP resulting in a release of hydrogen ion, ADP and a ribose 1,5-biphosphate. The latter compound is then phosphorylated through a ribose 1,5-bisphosphokinase resulting in the release of ADP and phosphoribosyl pyrophosphate. The latter compound is then involved in the purine nucleotides de novo biosynthesis pathway.PW000909MetabolicSecondary Metabolites: Histidine biosynthesisHistidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. This compound interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. This enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. This compound is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate. This compound reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. This compound reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate.
This compound interacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. This in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine.
L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.PW000984Metabolichistidine biosynthesisHistidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. This compound interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. This enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. This compound is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate. This compound reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. This compound reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate.
This compound interacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. This in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine.
L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.PW000810Metabolicpurine nucleotides de novo biosynthesisThe 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
PW000910Metabolicpurine nucleotides de novo biosynthesis 1435709748PW000960Metabolictryptophan metabolism IIThe biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan.
The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoAPW001916MetabolicThiamin diphosphate biosynthesisPW002028Metabolicadenine and adenosine salvage IThe salvage of adenine begins with adenine being transporter into the cytosol through a adeP hydrogen symporter. Once in the cytosol adenine is degraded by reacting with a ribose-1-phosphate through an adenosine phosphorylase resulting in the release of a phosphate and adenosine. Adenosine is then deaminated by reacting with water, a hydrogen ion and an adenosine deaminase resulting in the release of an ammonium and a inosine . Inosine then reacts with a phosphate through a inosine phosphorylase resulting in the release of a ribose 1-phosphate and a hypoxanthine. Hypoxanthine reacts with a PRPP through a hypoxanthine phosphoribosyltransferase resulting in the release of a pyrophosphate and a IMP molecule.PW002069Metabolicadenine and adenosine salvage IIIAdenosine is first incorporated into the cytosol through either a nupG or a nupC transporter. Once in the cytosol, adenosine is degraded into adenine by reacting with a water and a adenosine nucleosidase, releasing a D-ribofuranose and a adenine. The adenine then reacts with a PRPP through a adenine phosphoribosyltransferase resulting in the release of a pyrophosphate and an AMPPW002072Metabolicguanine and guanosine salvageGuanosine can be converted into guanine through a phosphate driven guanosine phosphorylase resulting in the release of an alpha-D-ribose 1 phosphate and a guanine. This compound in turn reacts with a PRPP through a guanine phosphoribosyltransferase resulting in the release of a pyrophosphate and a GMP.
Guanosine can also react with and ATP driven guanosine kinase resulting in the release of an ADP, s hydrogen ion and a GMP
PW002074Metabolicpurine nucleotides de novo biosynthesis 2The 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(5-Phosphoribosyl-5-carboxyaminoimidazole).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 dATPPW002033Metabolicpurine ribonucleosides degradationPurine ribonucleoside degradation leads to the production of alpha-D-ribose-1-phosphate.
Xanthosine is transported into the cytosol through a xapB. Once in the cytosol xanthosine interacts with phosphate through a xanthosine phosphorylase resulting in the release of a xanthine and a alpha-D-ribose-1-phosphate.
Adenosine is transported through a nupC or a nupG transporter, once inside the cytosol it can either react with a phosphate through a adenosine phosphorylase resultin in the release of a adenine and an alpha-D-ribose-1-phosphate. Adenosine reacts with water and hydrogen ion through a adenosine deaminase resulting in the release of ammonium and inosine. Inosine reacts with phosphate through a inosine phosphorylase resulting in the release of a hypoxanthine and an alpha-D-ribose-1-phosphate.
Guanosine reacts with a phosphate through a guanosine phosphorylase resulting in the release of a guanine and a alpha-D-ribose-1-phosphate.PW002076Metabolicadenine and adenosine salvage IIIPWY-6609adenine and adenosine salvage IIPWY-6605PRPP biosynthesis IPWY0-662NAD salvage pathway IPYRIDNUCSAL-PWYNAD biosynthesis I (from aspartate)PYRIDNUCSYN-PWYsalvage pathways of pyrimidine ribonucleotidesPWY0-163superpathway of 5-aminoimidazole ribonucleotide biosynthesisPWY-62775-aminoimidazole ribonucleotide biosynthesis IPWY-61215-aminoimidazole ribonucleotide biosynthesis IIPWY-6122guanine and guanosine salvage IPWY-6620uridine-5'-phosphate biosynthesisPWY-5686histidine biosynthesisHISTSYN-PWYtryptophan biosynthesisTRPSYN-PWYxanthine and xanthosine salvageSALVPURINE2-PWYPRPP biosynthesis IIPWY0-661Specdb::CMs2740Specdb::CMs37400Specdb::CMs163468Specdb::CMs1056651Specdb::CMs1056653Specdb::CMs1056655Specdb::CMs1056657Specdb::CMs1056659Specdb::CMs1056660Specdb::CMs1056662Specdb::CMs1056664Specdb::CMs1056666Specdb::CMs1056667Specdb::CMs1056669Specdb::CMs1056671Specdb::CMs1056673Specdb::CMs1056675Specdb::CMs1056677Specdb::CMs1056678Specdb::CMs1056680Specdb::CMs1056682Specdb::CMs1056684Specdb::CMs1056686Specdb::CMs1056688Specdb::CMs1056690Specdb::NmrOneD6402Specdb::NmrOneD6403Specdb::NmrOneD6404Specdb::NmrOneD6405Specdb::NmrOneD6406Specdb::NmrOneD6407Specdb::NmrOneD6408Specdb::NmrOneD6409Specdb::NmrOneD6410Specdb::NmrOneD6411Specdb::NmrOneD6412Specdb::NmrOneD6413Specdb::NmrOneD6414Specdb::NmrOneD6415Specdb::NmrOneD6416Specdb::NmrOneD6417Specdb::NmrOneD6418Specdb::NmrOneD6419Specdb::NmrOneD6420Specdb::NmrOneD6421Specdb::MsMs25517Specdb::MsMs25518Specdb::MsMs25519Specdb::MsMs32075Specdb::MsMs32076Specdb::MsMs32077Specdb::MsMs1471645Specdb::MsMs1471646Specdb::MsMs1471647Specdb::MsMs1471648Specdb::MsMs1471649Specdb::MsMs1471650Specdb::MsMs1471651Specdb::MsMs1471652Specdb::MsMs1471653Specdb::MsMs1471654Specdb::MsMs1471655Specdb::MsMs1471656Specdb::MsMs1471657Specdb::MsMs1471658Specdb::MsMs1471659Specdb::MsMs1471660Specdb::MsMs1473417Specdb::MsMs1473418Specdb::MsMs1475424HMDB0028073397062C0011917111PRPPPRPPhosphoribosyl pyrophosphateKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Snyder FF, Dyer C, Seegmiller JE, Goldblum RM, Mills GC, Schmalstieg FC: Substrate inhibition of adenosine phosphorylation in adenosine deaminase deficiency and adenosine-mediated inhibition of PP-ribose-P dependent nucleotide synthesis in hypoxanthine phosphoribosyltransferase deficient erythrocytes. J Inherit Metab Dis. 1988;11(2):174-83.2459496Gordon RB, Keough DT, Emmerson BT: HPRT-deficiency associated with normal PRPP concentration and APRT activity. J Inherit Metab Dis. 1987;10(1):82-8.2437388Nishida Y, Akaoka I, Nishizawa T, Maruki M, Maruki K: Synthesis and concentration of 5-phosphoribosyl-1-pyrophosphate in erythrocytes from patients with Down's syndrome. Ann Rheum Dis. 1977 Jun;36(3):261-3.141914Ghitis J, Schreiber C, Waxman S: Phosphate-induced phosphoribosylpyrophosphate elevations to assess deranged folate and purine nucleotide metabolism. Proc Soc Exp Biol Med. 1987 Oct;186(1):90-5.2442765Yamaoka T, Yano M, Kondo M, Sasaki H, Hino S, Katashima R, Moritani M, Itakura M: Feedback inhibition of amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide, DNA, and protein syntheses. J Biol Chem. 2001 Jun 15;276(24):21285-91. Epub 2001 Apr 4.11290738Blinov MN, Kamyshentsev MV, Luganova IS, Filanovskaia LI, Filippova VN: [Phosphoribosyl pyrophosphate and its metabolic enzymes in the erythrocytes in certain forms of anemia] Vopr Med Khim. 1976 Jul-Aug;22(4):456-62.194412Micheli V, Taddeo A: [Spectrophotometric assay of 5-phosphoribosyl-1-pyrophosphate synthetase (PRPP) in erythrocyte lysate (author's transl)] Quad Sclavo Diagn. 1981 Jun;17(2):209-15.6267652Sakuma R, Nishina T, Yamanaka H, Kamatani N, Nishioka K, Maeda M, Tsuji A: Phosphoribosylpyrophosphate synthetase in human erythrocytes: assay and kinetic studies using high-performance liquid chromatography. Clin Chim Acta. 1991 Dec 16;203(2-3):143-52.1663846Zoref-Shani E, Feinstein S, Frishberg Y, Bromberg Y, Sperling O: Kelley-Seegmiller syndrome due to a unique variant of hypoxanthine-guanine phosphoribosyltransferase: reduced affinity for 5-phosphoribosyl-1-pyrophosphate manifested only at low, physiological substrate concentrations. Biochim Biophys Acta. 2000 Feb 21;1500(2):197-203.10657589Sperling O, Boer P, Brosh S, Elazar E, Szeinberg A, de Vries A: Normal activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate in erythrocytes of patients with primary metabolic gout. Nutr Metab. 1975;18(4):217-23.172821Gorbach ZV: [Determination of phosphoribosyl pyrophosphate in the erythrocytes] Lab Delo. 1977;(12):724-5.75318Marcolongo R, Pompucci G, Micheli V: Familial distribution of increased erythrocyte PP-ribose-P levels. Adv Exp Med Biol. 1977;76A:280-6.193371Becker MA, Losman MJ, Itkin P, Simkin PA: Gout with superactive phosphoribosylpyrophosphate synthetase due to increased enzyme catalytic rate. J Lab Clin Med. 1982 Apr;99(4):495-511.6174658Tax WJ, Veerkamp JH: A simple and sensitive method for estimating the concentration and synthesis of 5-phosphoribosyl 1-pyrophosphate in red blood cells. Clin Chim Acta. 1977 Jul 15;78(2):209-16.195752MacDermot KD, Allsop J, Watts RW: The rate of purine synthesis de nova in blood mononuclear cells in vitro from patients with familial hyperuricaemic nephropathy. Clin Sci (Lond). 1984 Aug;67(2):249-58.6744792Emmerson BT, Gordon RB, Thompson L: Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease. Aust N Z J Med. 1975 Oct;5(5):440-6.1061547Zerez CR, Lachant NA, Tanaka KR: Decreased erythrocyte phosphoribosylpyrophosphate synthetase activity and impaired formation in thalassemia minor: a mechanism for decreased adenine nucleotide content. J Lab Clin Med. 1989 Jul;114(1):43-50.2544652Rylance HJ, Wallace RC, Nuki G: A method for the determination of 5-phosphoribosyl 1-pyrophosphate concentrations in erythrocytes using high-performance liquid chromatography. Anal Biochem. 1987 Feb 1;160(2):337-41.2437821Kane MA, Roth E, Raptis G, Schreiber C, Waxman S: Effect of intracellular folate concentration on the modulation of 5-fluorouracil cytotoxicity by the elevation of phosphoribosylpyrophosphate in cultured human KB cells. Cancer Res. 1987 Dec 15;47(24 Pt 1):6444-50.2445472Lachant NA, Zerez CR, Tanaka KR: Pyrimidine nucleotides impair phosphoribosylpyrophosphate (PRPP) synthetase subunit aggregation by sequestering magnesium. A mechanism for the decreased PRPP synthetase activity in hereditary erythrocyte pyrimidine 5'-nucleotidase deficiency. Biochim Biophys Acta. 1989 Jan 19;994(1):81-8.2535789Gross, Akiva; Abril, Obsidiana; Lewis, Jerome M.; Geresh, Shimona; Whitesides, George M. Practical synthesis of 5-phospho-D-ribosyl a-1-pyrophosphate (PRPP): enzymatic routes from ribose 5-phosphate or ribose. Journal of the American Chemical Society (Anthranilate synthase component IIP00904TRPG_ECOLItrpDhttp://ecmdb.ca/proteins/P00904.xmlRibose-phosphate pyrophosphokinaseP0A717KPRS_ECOLIprshttp://ecmdb.ca/proteins/P0A717.xmlOrotate phosphoribosyltransferaseP0A7E3PYRE_ECOLIpyrEhttp://ecmdb.ca/proteins/P0A7E3.xmlUracil phosphoribosyltransferaseP0A8F0UPP_ECOLIupphttp://ecmdb.ca/proteins/P0A8F0.xmlHypoxanthine phosphoribosyltransferaseP0A9M2HPRT_ECOLIhpthttp://ecmdb.ca/proteins/P0A9M2.xmlXanthine phosphoribosyltransferaseP0A9M5XGPT_ECOLIgpthttp://ecmdb.ca/proteins/P0A9M5.xmlAmidophosphoribosyltransferaseP0AG16PUR1_ECOLIpurFhttp://ecmdb.ca/proteins/P0AG16.xmlATP-binding protein phnNP16690PHNN_ECOLIphnNhttp://ecmdb.ca/proteins/P16690.xmlNicotinate phosphoribosyltransferaseP18133PNCB_ECOLIpncBhttp://ecmdb.ca/proteins/P18133.xmlNicotinate-nucleotide pyrophosphorylase [carboxylating]P30011NADC_ECOLInadChttp://ecmdb.ca/proteins/P30011.xmlATP phosphoribosyltransferaseP60757HIS1_ECOLIhisGhttp://ecmdb.ca/proteins/P60757.xmlAdenine phosphoribosyltransferaseP69503APT_ECOLIapthttp://ecmdb.ca/proteins/P69503.xmlGuanine + Phosphoribosyl pyrophosphate > Guanosine monophosphate + PyrophosphateR01229GUANPRIBOSYLTRAN-RXNHypoxanthine + Phosphoribosyl pyrophosphate <> Inosinic acid + PyrophosphateR01132HYPOXANPRIBOSYLTRAN-RXN2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphateR03348QUINOPRIBOTRANS-RXNPhosphoribosyl pyrophosphate + Xanthine <> Pyrophosphate + Xanthylic acidR02142XANPRIBOSYLTRAN-RXNAdenine + Phosphoribosyl pyrophosphate <> Adenosine monophosphate + PyrophosphateR00190ADENPRIBOSYLTRAN-RXNAdenosine triphosphate + Water + Nicotinic acid + Phosphoribosyl pyrophosphate > ADP + Nicotinamide ribotide + Phosphate + PyrophosphateAdenosine triphosphate + D-Ribose-5-phosphate <> Adenosine monophosphate + Hydrogen ion + Phosphoribosyl pyrophosphateR01049PRPPSYN-RXN2-Aminobenzoic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + N-(5-Phospho-D-ribosyl)anthranilateR01073PRTRANS-RXNAdenosine triphosphate + Phosphoribosyl pyrophosphate <> Pyrophosphate + Phosphoribosyl-ATPR01071ATPPHOSPHORIBOSYLTRANS-RXNL-Glutamine + Water + Phosphoribosyl pyrophosphate <> L-Glutamate + Pyrophosphate + 5-PhosphoribosylamineR01072PRPPAMIDOTRANS-RXNPhosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphateR00966URACIL-PRIBOSYLTRANS-RXNOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphateR01870OROPRIBTRANS-RXNAdenosine triphosphate + Ribose 1,5-bisphosphate <> ADP + Phosphoribosyl pyrophosphateR06836RXN0-1401Adenosine monophosphate + Pyrophosphate <> Adenine + Phosphoribosyl pyrophosphateR00190Uridine 5'-monophosphate + Pyrophosphate <> Uracil + Phosphoribosyl pyrophosphateR00966Adenosine triphosphate + D-Ribose-5-phosphate <> Adenosine monophosphate + Phosphoribosyl pyrophosphateR01049Phosphoribosyl-ATP + Pyrophosphate <> Adenosine triphosphate + Phosphoribosyl pyrophosphateR010715-Phosphoribosylamine + Pyrophosphate + L-Glutamate <> L-Glutamine + Phosphoribosyl pyrophosphate + WaterR01072N-(5-Phospho-D-ribosyl)anthranilate + Pyrophosphate <> 2-Aminobenzoic acid + Phosphoribosyl pyrophosphateR01073Inosinic acid + Pyrophosphate <> Hypoxanthine + Phosphoribosyl pyrophosphateR01132Guanosine monophosphate + Pyrophosphate <> Guanine + Phosphoribosyl pyrophosphateR01229Nicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + PhosphateR01724Xanthylic acid + Pyrophosphate <> Xanthine + Phosphoribosyl pyrophosphateR02142Nicotinamide ribotide + Pyrophosphate + Carbon dioxide <> Quinolinic acid + Phosphoribosyl pyrophosphateR03348AICAR + Pyrophosphate <> 5-Amino-4-imidazolecarboxyamide + Phosphoribosyl pyrophosphateR043786-Mercaptopurine + Phosphoribosyl pyrophosphate <> 6-Thioinosine-5'-monophosphate + PyrophosphateR082376-Methylmercaptopurine + Phosphoribosyl pyrophosphate <> 6-Methylthiopurine 5'-monophosphate ribonucleotide + PyrophosphateR08238Thioguanine + Phosphoribosyl pyrophosphate <> 6-Thioguanosine monophosphate + PyrophosphateR08245Pyrophosphate + Adenosine monophosphate < Phosphoribosyl pyrophosphate + AdenineADENPRIBOSYLTRAN-RXNPyrophosphate + Inosinic acid < Phosphoribosyl pyrophosphate + HypoxanthineHYPOXANPRIBOSYLTRAN-RXNNicotinamide ribotide + Pyrophosphate < Hydrogen ion + Nicotinic acid + Phosphoribosyl pyrophosphateR01724NICOTINATEPRIBOSYLTRANS-RXN5-Phosphoribosylamine + Pyrophosphate + L-Glutamate < Phosphoribosyl pyrophosphate + L-Glutamine + WaterR01072PRPPAMIDOTRANS-RXNN-(5-Phospho-D-ribosyl)anthranilate + Pyrophosphate < 2-Aminobenzoic acid + Phosphoribosyl pyrophosphatePRTRANS-RXNNicotinamide ribotide + Pyrophosphate + Carbon dioxide < Phosphoribosyl pyrophosphate + Quinolinic acid + Hydrogen ionQUINOPRIBOTRANS-RXNRibose 1,5-bisphosphate + Adenosine triphosphate > Phosphoribosyl pyrophosphate + ADPR06836RXN0-1401Pyrophosphate + Uridine 5'-monophosphate < Phosphoribosyl pyrophosphate + UracilURACIL-PRIBOSYLTRANS-RXNXanthylic acid + Pyrophosphate < Xanthine + Phosphoribosyl pyrophosphateR02142XANPRIBOSYLTRAN-RXNAdenosine monophosphate + Pyrophosphate > Adenine + Phosphoribosyl pyrophosphatePhosphoribosyl-ATP + Pyrophosphate > Adenosine triphosphate + Phosphoribosyl pyrophosphateInosinic acid + Pyrophosphate > Hypoxanthine + Phosphoribosyl pyrophosphateAdenosine triphosphate + D-Ribose-5-phosphate > Adenosine monophosphate + Phosphoribosyl pyrophosphateNicotinamide ribotide + Pyrophosphate + Carbon dioxide > Quinolinic acid + Phosphoribosyl pyrophosphateNicotinamide ribotide + Pyrophosphate > Nicotinic acid + Phosphoribosyl pyrophosphateR01724NICOTINATEPRIBOSYLTRANS-RXN5-Phosphoribosylamine + Pyrophosphate + L-Glutamate > L-Glutamine + Phosphoribosyl pyrophosphate + WaterOrotidylic acid + Pyrophosphate > Orotic acid + Phosphoribosyl pyrophosphateN-(5-Phospho-D-ribosyl)anthranilate + Pyrophosphate > 2-Aminobenzoic acid + Phosphoribosyl pyrophosphateUridine 5'-monophosphate + Pyrophosphate > Uracil + Phosphoribosyl pyrophosphateXanthylic acid + Pyrophosphate > Phosphoribosyl pyrophosphate + XanthinePhosphoribosyl pyrophosphate + Hydrogen ion > Pyrophosphate + Phosphoribosyl-ATP + Phosphoribosyl-ATPPW_R0028652-Aminobenzoic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + N-(5-phosphoribosyl)-anthranilate + N-(5-phosphoribosyl)-anthranilatePW_R002895Quinolinic acid + Hydrogen ion + Phosphoribosyl pyrophosphate > Carbon dioxide + Pyrophosphate + nicotinate beta-D-ribonucleotide + Nicotinamide ribotidePW_R003009Nicotinic acid + Water + Adenosine triphosphate + Phosphoribosyl pyrophosphate > Phosphate + Adenosine diphosphate + Pyrophosphate + nicotinate beta-D-ribonucleotide + ADP + Nicotinamide ribotidePW_R003016D-Ribose-5-phosphate + Adenosine triphosphate > Hydrogen ion + Adenosine monophosphate + Phosphoribosyl pyrophosphatePW_R003406Ribose 1,5-bisphosphate + Adenosine triphosphate + Ribose 1,5-bisphosphate > Adenosine diphosphate + Phosphoribosyl pyrophosphate + ADPPW_R003409Phosphoribosyl pyrophosphate + Water + L-Glutamine > 5-Phosphoribosylamine + L-Glutamic acid + Pyrophosphate + 5-Phosphoribosylamine + L-GlutamatePW_R003410Orotic acid + Phosphoribosyl pyrophosphate > Pyrophosphate + Orotidylic acidPW_R003529Hypoxanthine + Phosphoribosyl pyrophosphate > Inosinic acid + PyrophosphatePW_R006052Guanine + Phosphoribosyl pyrophosphate > Pyrophosphate + Guanosine monophosphatePW_R006059Adenine + Phosphoribosyl pyrophosphate > Pyrophosphate + Adenosine monophosphatePW_R006055Xanthine + Phosphoribosyl pyrophosphate > Xanthylic acid + PyrophosphatePW_R006088Guanine + Phosphoribosyl pyrophosphate > Guanosine monophosphate + PyrophosphateL-Glutamine + Water + Phosphoribosyl pyrophosphate <> L-Glutamate + Pyrophosphate +5 5-Phosphoribosylamine5 5-Phosphoribosylamine + Pyrophosphate + L-Glutamate <> L-Glutamine + Phosphoribosyl pyrophosphate + WaterAdenosine triphosphate + Phosphoribosyl pyrophosphate <> Pyrophosphate + Phosphoribosyl-ATPPhosphoribosyl-ATP + Pyrophosphate <> Adenosine triphosphate + Phosphoribosyl pyrophosphate2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphatePhosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphateAdenosine triphosphate + D-Ribose-5-phosphate <> Adenosine monophosphate + Hydrogen ion + Phosphoribosyl pyrophosphateNicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + PhosphateOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphateGuanine + Phosphoribosyl pyrophosphate > Guanosine monophosphate + PyrophosphateL-Glutamine + Water + Phosphoribosyl pyrophosphate <> L-Glutamate + Pyrophosphate +5 5-PhosphoribosylamineAdenosine triphosphate + Phosphoribosyl pyrophosphate <> Pyrophosphate + Phosphoribosyl-ATP2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphatePhosphoribosyl pyrophosphate + Uracil <> Pyrophosphate + Uridine 5'-monophosphateNicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + PhosphateOrotidylic acid + Pyrophosphate <> Orotic acid + Phosphoribosyl pyrophosphateGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture258.0uM0.037 oCK12 NCM3722Mid-Log Phase10320000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerolShake flask and filter culture153.0uM0.037 oCK12 NCM3722Mid-Log Phase6120000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetateShake flask and filter culture94.4uM0.037 oCK12 NCM3722Mid-Log Phase3776000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621