MetaCyc Pathway: base-degraded thiamin salvage

Enzyme View:

Pathway diagram: base-degraded thiamin salvage

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

Some taxa known to possess this pathway include ? : Bacillus halodurans [Jenkins07], Bacillus subtilis subtilis 168 [Jenkins07], Pyrococcus furiosus [Benach05], Saccharomyces cerevisiae [French11]

Expected Taxonomic Range: Archaea , Bacteria , Fungi

General Background

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 [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 thiamin-containing husk [Begley96]. Thiamin is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g. Plasmodium ), but not by higher eukaryotes, which must obtain it through their diet.

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 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 thiamin 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 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 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 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].

Created 14-Sep-2011 by Caspi R , SRI International
Revised 27-Aug-2013 by Foerster H , Boyce Thompson Institute


Begley96: Begley, T.P. (1996). "The biosynthesis and degradation of thiamin (vitamin B1)." Natural products report.

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

French11: French JB, Begley TP, Ealick SE (2011). "Structure of trifunctional THI20 from yeast." Acta Crystallogr D Biol Crystallogr 67(Pt 9);784-91. PMID: 21904031

Fujita54: Fujita, A., Nose, Y., Kuratani, K. (1954). "The second type of bacterial thiaminase." J Vitaminol (Kyoto) 1(1);1-7. PMID: 13243520

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

Jenkins07: Jenkins AH, Schyns G, Potot S, Sun G, Begley TP (2007). "A new thiamin salvage pathway." Nat Chem Biol 3(8);492-7. PMID: 17618314

Jenkins08: Jenkins AL, Zhang Y, Ealick SE, Begley TP (2008). "Mutagenesis studies on TenA: a thiamin salvage enzyme from Bacillus subtilis." Bioorg Chem 36(1);29-32. PMID: 18054064

Lawhorn04a: Lawhorn BG, Mehl RA, Begley TP (2004). "Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction." Org Biomol Chem 2(17);2538-46. PMID: 15326535

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

GOA00: GOA (2000). "Gene Ontology annotation based on Swiss-Prot keyword mapping."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Fri Mar 27, 2015, BIOCYC13B.