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Pathway Description
Thiamin Diphosphate Biosynthesis
Escherichia coli
Metabolic Pathway
The biosynthesis of thiamin begins with a PRPP being degraded by reacting with a water molecule and an L-glutamine through a amidophosphoribosyl transferase resulting in the release of an L-glutamate, a diphosphate and a 5-phospho-beta-d-ribosylamine(PRA). The latter compound, PRA, is further degrade through a phosphoribosylamine glycine ligase by reacting with a glycine and an ATP. This reaction results in the release of a hydrogen ion, an ADP, a phosphate and a N1-(5-phospho-beta-d-ribosyl)glycinamide(GAR). GAR can be metabolized by two different phosphoribosylglycinamide formyltransferase. GAR reacts with a N10-formyl tetrahydrofolate, in this case 10-formyl-tetrahydrofolate mono-L-glutamate, through a phosphoribosylglycinamide formyltransferase 1 resulting in the release of a hydroge ion, a tetrahydrofolate and a N2-formyl-N1-(5-phospho-Beta-D-ribosyl)glycinamide(FGAR). On the other hand, GAR can react with a formate and an ATP molecule through a phosphoribosylglycinamide formyltransferase 2 resulting in a release of a ADP, a phosphate, a hydrogen ion and a FGAR. The FGAR compound gets degraded by interacting with a water molecule, an L-glutamine and an ATP molecule thorugh a phosphoribosylformylglycinamide synthase resulting in the release of a L-glutamate, a phosphate, an ADP molecule, a hydrogen ion and a 2-(formamido)-N1-(5-phopho-Beta-D-ribosyl)acetamidine (FGAM). This compound is further degraded by reacting with an ATP molecule through a phosphoribosylformylglycinamide cyclo-ligase resulting in the release of a phosphate, an ADP, a hydrogen ion and a 5-amino-1-(5-phospho-beta-d-ribosyl)imidazole (AIR). The AIR molecule is degraded by reacting with a S-adenosyl-L-methionine through a HMP-P synthase resulting in the release of 3 hydrogen ions, a carbon monoxide, a formate molecule, L-methionine, 5'-deoxyadenosine and 4- amino-2-methyl-5-phophomethylpyrimidine (HMP-P). This resulting compound is phosphorylated thorugh a ATP driven phosphohydroxymethylpyrimidine kinase resulting in the release of an ADP and 4-amino-2-methyl-5-diphosphomethylpyrimidine (HMP-PP). The resulting compound interacts with a thiazole tautomer and 2 hydrogen ion through a Thiamine phosphate synthase resulting in the release of a pyrophosphate, a carbon dioxide molecule and Thiamin phosphate. This compound is phosphorylated through an ATP driven thiamin monophosphate kinase resulting in a release of an ADP and a thiamin diphosphate.
References
Thiamin Diphosphate Biosynthesis References
Nygaard P, Smith JM: Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli. J Bacteriol. 1993 Jun;175(11):3591-7.
Pubmed: 8501063
Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE: Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat Chem Biol. 2008 Dec;4(12):758-65. doi: 10.1038/nchembio.121. Epub 2008 Oct 26.
Pubmed: 18953358
Chatterjee A, Hazra AB, Abdelwahed S, Hilmey DG, Begley TP: A "radical dance" in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase. Angew Chem Int Ed Engl. 2010 Nov 8;49(46):8653-6. doi: 10.1002/anie.201003419.
Pubmed: 20886485
Lawhorn BG, Mehl RA, Begley TP: Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction. Org Biomol Chem. 2004 Sep 7;2(17):2538-46. doi: 10.1039/B405429F. Epub 2004 Aug 11.
Pubmed: 15326535
Park JH, Burns K, Kinsland C, Begley TP: 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. 2004 Mar;186(5):1571-3.
Pubmed: 14973012
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