This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: formylaminopyrimidine salvage
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Thiamin Biosynthesis → Thiamin Salvage|
Thiamin diphosphate, also known as vitamin B1, is known to play a fundamental role in energy metabolism. It is an essential cofactor for a variety of enzymes such as transketolase, pyruvate dehydrogenase, pyruvate decarboxylase, and α-ketoglutarate dehydrogenase [Lawhorn04]. Its discovery followed from the original early research on the anti-beriberi factor found in rice bran. Beriberi, a neurological disease, was particularly prevalent in Asia, where the refining of rice resulted in the removal of the thiamin-containing husk [Begley96]. Thiamin is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g. Plasmodium
About This Pathway
Since the de novo biosynthesis of thiamin diphosphate is a very complex process, many organisms possess various salvage pathways that enable them to rescue thiamin fragments obtained from the environment. This pathway describes the salvage of base-degraded thiamin compounds, and starts with formylaminopyrimidine, a compound that is generated by base-mediated degradation of the thiazolium moiety of thiamin [Jenkins07].
Formylaminopyrimidine is transported into the cell and deformylated by N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine deformylase (ylmB). The resulting aminomethylpyrimidine is converted to hydroxymethylpyrimidine (HMP) by 4-amino-5-aminomethyl-2-methylpyrimidine hydrolase (TenA, thiaminase II). The salvaged HMP is then phosphorylated to form 4-amino-2-methyl-5-diphosphomethylpyrimidine, which is incorporated into the de novo thiamin biosynthetic pathway [Jenkins08].
In Saccharomyces cerevisiae the trifunctional fusion protein THI20p is also able to hydrolyze aminomethylpyrimidine to form hydroxymethylpyrimidine in this salvage pathway. The enzyme which exhibits HMP/HMP-P kinase and thiaminase II activity was a puzzle for a long time as it apparently fuses thiamin biosynthetic and degradation activities in one enzyme. However, those activities, encoded by several monomers in bacteria, fit well in the thiamin salvage pathway as they hydrolyze thiamin and similar compounds, e.g. aminomethylpyrimidine to hydroxymethylpyrimidine which is immediately phosphorylated by the HMP/HMP-P kinase activity of the same protein [Haas05, Onozuka08, French11].
The key enzyme in this pathway, thiaminase II, was considered a thiamin degradation enzyme for a long time after its discovery [Fujita54], since it is able to catalyze the hydrolysis of thiamine to its thiazole and pyrimidine components. Its true nature as a salvage enzyme was revealed only five decades later [Jenkins07].
Benach05: Benach J, Edstrom WC, Lee I, Das K, Cooper B, Xiao R, Liu J, Rost B, Acton TB, Montelione GT, Hunt JF (2005). "The 2.35 A structure of the TenA homolog from Pyrococcus furiosus supports an enzymatic function in thiamine metabolism." Acta Crystallogr D Biol Crystallogr 61(Pt 5);589-98. PMID: 15858269
Haas05: Haas AL, Laun NP, Begley TP (2005). "Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activities." Bioorg Chem 33(4);338-44. PMID: 15967475
Onozuka08: Onozuka M, Konno H, Kawasaki Y, Akaji K, Nosaka K (2008). "Involvement of thiaminase II encoded by the THI20 gene in thiamin salvage of Saccharomyces cerevisiae." FEMS Yeast Res 8(2);266-75. PMID: 18028398
Toms05: Toms AV, Haas AL, Park JH, Begley TP, Ealick SE (2005). "Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase II." Biochemistry 44(7);2319-29. PMID: 15709744
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