If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: purine fermentation
|Superclasses:||Degradation/Utilization/Assimilation → Nucleosides and Nucleotides Degradation → Purine Nucleotides Degradation|
|Generation of Precursor Metabolites and Energy → Fermentation|
Expected Taxonomic Range: Firmicutes
The anaerobic fermentation of purines was first observed in the organisms Gottschalkia acidurici and Clostridium cylindrosporum in 1942 [Barker42]. These organisms can utilize only a small number of purine derivatives including purine, 8-hydroxypurine, 6,8-dihydroxypurine, hypoxanthine, guanine and xanthine under anaerobic conditions as carbon, nitrogen, and energy sources, and are unable to ferment any other organic compounds. The purines urate, guanine and xanthine are readily decomposed by these organisms, while growth on hypoxanthine is appreciably slower, and adenine does not support growth at all [Barker42]. The slow growth on hypoxanthine was explained upon the characterization of the enzyme xanthine dehydrogenase from Clostridium cylindrosporum. The enzyme was shown to catalyze not only the reversible conversion of urate to xanthine, but also the oxidation of most other substrates, sometimes requiring multiple steps, eventually converging at xanthine. While the enzyme is able to oxidize hypoxanthine to xanthine, this reaction proceeded very slowly [RABINOWITZ, 1956].
The products of this fermentation were identified as ammonia, CO2 and acetate. Early studies using tracer experiments revealed that glycine, formate and L-serine were intermediates of the pathway [Barker41, Radin53, Rabinowitz56, Beck56].
Work by Rabinowitz and coworkers helped discover many of the intermediates of this pathway. The intermediates 4-amino-5-imidazole carboxylate and 4-aminoimidazole were discovered first [Rabinowitz56a], followed by 4-ureido-5-imidazole carboxylate [Rabinowitz56b] and N-formimino-glycine [Pricer56].
The next step of the pathway is the transfer of a formimino group from N-formimino-glycine to tetrahydropteroyl mono-L-glutamate, generating glycine and a 5-formiminotetrahydrofolate. The discovery of this step eventually lead Rabinowitz to focus on folate metabolism, leading to significant progress in the understanding of that field.
Deciphering the later steps of the pathway was more complex. Formate is generated via the intermediates 5,10-methenyltetrahydrofolate mono-L-glutamate and 10-formyl-tetrahydrofolate mono-L-glutamate, by the enzymes formimidoyltetrahydrofolate cyclodeaminase (EC 22.214.171.124), methenyltetrahydrofolate cyclohydrolase (EC 126.96.36.199) and formate--tetrahydrofolate ligase (EC 188.8.131.52) [Himes62]. Formate is then converted to CO2 by an NAD-dependent formate dehydrogenase.
Acetate is generated from pyruvate as described below.
Rresearch conducted about two decades after the intial characterization of the pathway has shown that several branches of this pathway are modified when the cells are supplied with selenium, due to the activation of certain L-selenocysteine-containing enzymes. While in the pathway described here purines are oxidized largly via urate by the enzyme xanthine dehydrogenase, in selenium-supplemented cells a second enzyme, purine hydroxylase, oxidizes purines directly to xanthine. In addition, a selenium-dependent glycine reductase reduces glycine directly to acetyl phosphate, bypassing the branch of the pathway described below. The selenium-dependent pathway is described in purine nucleobases degradation I (anaerobic).
About This Pathway
Early studies showed that one of the carbons in the acetate that is produced originates from glycine, while the other carbon originates from carbon C5 of urate [Rabinowitz56]. In addition, pyruvate and L-serine were also shown to be intermediates in the pathway [Radin53, SchieferUllrich84]. A preliminary suggestion for a pathway that accomodates all of these observations has been suggested in 1956 [Beck56], followed by a more refined model in 1961 [Sagers61]. As mentioned above, the splitting of N-formimino-glycine generates a glycine molecule and a formimino group that is transferred to tetrahydropteroyl mono-L-glutamate, forming a 5-formiminotetrahydrofolate [Uyeda65]. According to the model, a 5-formiminotetrahydrofolate is converted to 5,10-methenyltetrahydrofolate mono-L-glutamate [Uyeda67] and then to 5,10-methylenetetrahydropteroyl mono-L-glutamate [Uyeda67a]. The later transfers the C1 group to the glycine molecule formed earlier, releasing the folate cofactor and generating L-serine [Hougland79]. L-serine is then split into ammonia and pyruvate [Benziman60], which is converted to acetate via acetyl-CoA and acetyl phosphate [Sagers61]. this last step, catalyzed by acetate kinase, probably represents the major energy-yielding reaction during purine fermentation by these organisms.
Variants: pseudouridine degradation , purine deoxyribonucleosides degradation , purine deoxyribonucleosides degradation I , purine nucleobases degradation I (anaerobic) , purine nucleotides degradation I (plants) , purine nucleotides degradation II (aerobic) , purine ribonucleosides degradation , urate biosynthesis/inosine 5'-phosphate degradation
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Aceti88: Aceti DJ, Ferry JG (1988). "Purification and characterization of acetate kinase from acetate-grown Methanosarcina thermophila. Evidence for regulation of synthesis." J Biol Chem 1988;263(30);15444-8. PMID: 2844814
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Beckmann97: Beckmann K, Dzuibany C, Biehler K, Fock H, Hell R, Migge A, Becker TW (1997). "Photosynthesis and fluorescence quenching, and the mRNA levels of plastidic glutamine synthetase or of mitochondrial serine hydroxymethyltransferase (SHMT) in the leaves of the wild-type and of the SHMT-deficient stm mutant of Arabidopsis thaliana in relation to the rate of photorespiration." Planta 202(3);379-86. PMID: 9232907
Beh93: Beh M, Strauss G, Huber R, Stetter K-O, Fuchs G (1993). "Enzymes of the reductive citric acid cycle in the autotrophic eubacterium Aquifex pyrophilus and in the archaebacterium Thermoproteus neutrophilus." Arch Microbiol 160: 306-311.
Bergmeyer63: Bergmeyer, H.U., Holz, G., Klotzsch, H., Lang, G. (1963). "[Phosphotransacetylase from Clostridium kluyveri. Culture of the bacterium, isolation, crystallization and properties of the enzyme.]." Biochem Z 338;114-21. PMID: 14087284
Blamey93: Blamey JM, Adams MW (1993). "Purification and characterization of pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus." Biochim Biophys Acta 1161(1);19-27. PMID: 8380721
Blamey94: Blamey JM, Adams MW (1994). "Characterization of an ancestral type of pyruvate ferredoxin oxidoreductase from the hyperthermophilic bacterium, Thermotoga maritima." Biochemistry 1994;33(4);1000-7. PMID: 8305426
Blaschkowski82: Blaschkowski HP, Neuer G, Ludwig-Festl M, Knappe J (1982). "Routes of flavodoxin and ferredoxin reduction in Escherichia coli. CoA-acylating pyruvate: flavodoxin and NADPH: flavodoxin oxidoreductases participating in the activation of pyruvate formate-lyase." Eur J Biochem 123(3);563-9. PMID: 7042345
Bock99: Bock AK, Glasemacher J, Schmidt R, Schonheit P (1999). "Purification and characterization of two extremely thermostable enzymes, phosphate acetyltransferase and acetate kinase, from the hyperthermophilic eubacterium Thermotoga maritima." J Bacteriol 1999;181(6);1861-7. PMID: 10074080
Bologna10: Bologna FP, Campos-Bermudez VA, Saavedra DD, Andreo CS, Drincovich MF (2010). "Characterization of Escherichia coli EutD: a phosphotransacetylase of the ethanolamine operon." J Microbiol 48(5);629-36. PMID: 21046341
Boynton96: Boynton ZL, Bennett GN, Rudolph FB (1996). "Cloning, sequencing, and expression of genes encoding phosphotransacetylase and acetate kinase from Clostridium acetobutylicum ATCC 824." Appl Environ Microbiol 1996;62(8);2758-66. PMID: 8702268
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