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, base-degraded thiamin salvage
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Thiamine Biosynthesis → Thiamine Salvage|
Thiamine 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
pyruvate decarboxylase, and
[Lawhorn04a]. 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 thiamine-containing husk
[Begley96]. Thiamine is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g.
About This Pathway
Since the de novo biosynthesis of thiamine diphosphate is a very complex process, many organisms possess various salvage pathways that enable them to rescue thiamine fragments obtained from the environment. This pathway describes the salvage of base-degraded thiamine compounds, and starts with formylaminopyrimidine, a compound that is generated by base-mediated degradation of the thiazolium moiety of thiamine [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 4-amino-2-methyl-5-pyrimidinemethanol (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 thiamine biosynthetic pathway [Jenkins08].
In Saccharomyces cerevisiae the trifunctional fusion protein THI20p is also able to hydrolyze aminomethylpyrimidine to form 4-amino-2-methyl-5-pyrimidinemethanol 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 thiamine biosynthetic and degradation activities in one enzyme. However, those activities, encoded by several monomers in bacteria, fit well in the thiamine salvage pathway as they hydrolyze thiamine and similar compounds, e.g. aminomethylpyrimidine to 4-amino-2-methyl-5-pyrimidinemethanol 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 thiamine 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].
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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