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: HMP-PP biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Thiamin Biosynthesis|
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
Thiamin biosynthesis is composed of the separate formation of the pyrimidine and thiazole moieties, which are subsequently coupled to form thiamin phosphate (see for example thiamin diphosphate biosynthesis II (Bacillus)).
About This Pathway
This pathway describes the synthesis of the pyrimidine moiety of thiamin. Starting with 5-amino-1-(5-phospho-β-D-ribosyl)imidazole, an intermdiate in purine biosynthesis, two enzymatic steps, catalyzed by ThiC and ThiD, produce 4-amino-2-methyl-5-diphosphomethylpyrimidine. The first reaction is one of the most complicated rearrangement reactions known. The ThiC enzyme belongs to the radical SAM family, all members of which utilize S-adenosyl-L-methionine (SAM) to generate an 5'-deoxyadenosyl radical that in turn serves as an oxidant for a wide variety of enzymatic reactions [Chatterjee08]. The first stage of catalysis is the reduction of SAM to produce L-methionine and a 5-deoxyadenosyl radical, which is generated at the active site. The radical reacts directly with the substrate to catalyze a complex rearrangement reaction that includes two iterative hydrogen atom abstractions (which necessitates the regeneration of the radical following the first abstraction). C1' and C3' of the substrate, which are not inorporated into the product, are converted to formate and carbon monoxide, respectively [Chatterjee10].
The second enzyme, ThiD, is a simple kinase. It is a bifunctional enzyme, and can also phosphorylate hydroxymethylpyrimidine, as a part of a thiamin salvage pathway (see thiamin salvage II) [Park04a].
Variants: 4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis (yeast) , thiamin diphosphate biosynthesis I (E. coli) , thiamin diphosphate biosynthesis II (Bacillus) , thiamin diphosphate biosynthesis III (Staphylococcus) , thiamin diphosphate biosynthesis IV (eukaryotes) , thiamin formation from pyrithiamine and oxythiamine (yeast) , thiamin triphosphate metabolism , thiazole biosynthesis I (E. coli) , thiazole biosynthesis II (Bacillus) , thiazole biosynthesis III (eukaryotes)
Unification Links: EcoCyc:PWY-6890
Chatterjee08: Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE (2008). "Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily." Nat Chem Biol 4(12);758-65. PMID: 18953358
Chatterjee10: Chatterjee A, Hazra AB, Abdelwahed S, Hilmey DG, Begley TP (2010). "A "Radical Dance" in Thiamin Biosynthesis: Mechanistic Analysis of the Bacterial Hydroxymethylpyrimidine Phosphate Synthase." Angew Chem Int Ed Engl. PMID: 20886485
Park04a: Park JH, Burns K, Kinsland C, Begley TP (2004). "Characterization of two kinases involved in thiamine pyrophosphate and pyridoxal phosphate biosynthesis in Bacillus subtilis: 4-amino-5-hydroxymethyl-2methylpyrimidine kinase and pyridoxal kinase." J Bacteriol 186(5);1571-3. PMID: 14973012
Ajjawi07: Ajjawi I, Tsegaye Y, Shintani D (2007). "Determination of the genetic, molecular, and biochemical basis of the Arabidopsis thaliana thiamin auxotroph th1." Arch Biochem Biophys 459(1);107-14. PMID: 17174261
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Dougherty06: Dougherty MJ, Downs DM (2006). "A connection between iron-sulfur cluster metabolism and the biosynthesis of 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate in Salmonella enterica." Microbiology 152(Pt 8);2345-53. PMID: 16849799
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
Kim98: Kim YS, Nosaka K, Downs DM, Kwak JM, Park D, Chung IK, Nam HG (1998). "A Brassica cDNA clone encoding a bifunctional hydroxymethylpyrimidine kinase/thiamin-phosphate pyrophosphorylase involved in thiamin biosynthesis." Plant Mol Biol 37(6);955-66. PMID: 9700068
Komeda88: Komeda Y, Tanaka M, Nishimune T (1988). "A th-1 Mutant of Arabidopsis thaliana Is Defective for a Thiamin-Phosphate-Synthesizing Enzyme: Thiamin Phosphate Pyrophosphorylase." Plant Physiol 88(2);248-250. PMID: 16666289
Llorente99: Llorente B, Fairhead C, Dujon B (1999). "Genetic redundancy and gene fusion in the genome of the Baker's yeast Saccharomyces cerevisiae: functional characterization of a three-member gene family involved in the thiamine biosynthetic pathway." Mol Microbiol 32(6);1140-52. PMID: 10383756
LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493