Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase[1] is a thiamine (vitamin B1) derivative which is produced by the enzymethiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all living systems, in which it catalyzes several biochemical reactions.
Thiamine pyrophosphate is synthesized in the cytosol and is required in the cytosol for the activity of transketolase and in the mitochondria for the activity of pyruvate-, oxoglutarate- and branched chain keto acid dehydrogenases. To date, the yeast ThPP carrier (Tpc1p) the human Tpc and the Drosophila melanogaster have been identified as being responsible for the mitochondrial transport of ThPP and ThMP.[2][3][4] It was first discovered as an essential nutrient (vitamin) in humans through its link with the peripheral nervous systemdiseaseberiberi, which results from a deficiency of thiamine in the diet.[5]
TPP works as a coenzyme in many enzymatic reactions, such as:
The part of TPP molecule that is most commonly involved in reactions is the thiazole ring, which contains nitrogen and sulfur. Thus, the thiazole ring is the "reagent portion" of the molecule. The C2 of this ring is capable of acting as an acid by donating its proton and forming a carbanion.[7] Normally, reactions that form carbanions are highly unfavorable, but the positive charge on the tetravalent nitrogen just adjacent to the carbanion stabilizes the negative charge, making the reaction much more favorable.[7] A compound with positive and negative charges on adjacent atoms is called an ylide, so sometimes the carbanion form of TPP is referred to as the "ylide form".[5][8]
Reaction mechanismsedit
In several reactions, including that of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, TPP catalyses the reversible decarboxylation reaction (aka cleavage of a substrate compound at a carbon-carbon bond connecting a carbonyl group to an adjacent reactive group—usually a carboxylic acid or an alcohol). It achieves this in four basic steps:
The carbanion of the TPP ylid nucleophilically attacks the carbonyl group on the substrate. (This forms a single bond between the TPP and the substrate.)
The target bond on the substrate is broken, and its electrons are pushed towards the TPP. This creates a double bond between the substrate carbon and the TPP carbon and pushes the electrons in the N-C double bond in TPP entirely onto the nitrogen atom, reducing it from a positive to neutral form.
In what is essentially the reverse of step two, the electrons push back in the opposite direction forming a new bond between the substrate carbon and another atom. (In the case of the decarboxylases, this creates a new carbon-hydrogen bond. In the case of transketolase, this attacks a new substrate molecule to form a new carbon-carbon bond.)
In what is essentially the reverse of step one, the TPP-substrate bond is broken, reforming the TPP ylid and the substrate carbonyl.
The TPP thiazolium ring can be deprotonated at C2 to become an ylid.
A full view of TPP. The arrow indicates the acidic proton.
^Pietrzak I (1995). "[Vitamin disturbances in chronic renal insufficiency. I. Water soluble vitamins]". Przegla̧D Lekarski (in Polish). 52 (10): 522–5. PMID 8834846.
^Marobbio, C. M. T.; Vozza, A.; Harding, M.; Bisaccia, F.; Palmieri, F.; Walker, J. E. (2002-11-01). "Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate". The EMBO Journal. 21 (21): 5653–5661. doi:10.1093/emboj/cdf583. ISSN 0261-4189. PMC131080. PMID 12411483.
^Iacopetta, Domenico; Carrisi, Chiara; De Filippis, Giuseppina; Calcagnile, Valeria M.; Cappello, Anna R.; Chimento, Adele; Curcio, Rosita; Santoro, Antonella; Vozza, Angelo (2010-03-01). "The biochemical properties of the mitochondrial thiamine pyrophosphate carrier from Drosophila melanogaster". FEBS Journal. 277 (5): 1172–1181. doi:10.1111/j.1742-4658.2009.07550.x. ISSN 1742-4658. PMID 20121944.
^Lindhurst, Marjorie J.; Fiermonte, Giuseppe; Song, Shiwei; Struys, Eduard; Leonardis, Francesco De; Schwartzberg, Pamela L.; Chen, Amy; Castegna, Alessandra; Verhoeven, Nanda (2006-10-24). "Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia". Proceedings of the National Academy of Sciences. 103 (43): 15927–15932. Bibcode:2006PNAS..10315927L. doi:10.1073/pnas.0607661103. ISSN 0027-8424. PMC1595310. PMID 17035501.
^ abPavia, Donald L., Gary M. Lampman, George S. Kritz, Randall G. Engel (2006). Introduction to Organic Laboratory Techniques (4th Ed.). Thomson Brooks/Cole. pp. 304–5. ISBN978-0-495-28069-9.{{cite book}}: CS1 maint: multiple names: authors list (link)
^. Georgia State University. Archived from the original on 2011-07-16. Retrieved 2009-02-07.
^ abBegley, Tadhg P.; Ealick, Steven E. (2010-01-01), Liu, Hung-Wen (Ben); Mander, Lew (eds.), "7.15 - Thiamin Biosynthesis", Comprehensive Natural Products II, Oxford: Elsevier, pp. 547–559, doi:10.1016/b978-008045382-8.00148-9, ISBN978-0-08-045382-8, retrieved 2020-12-16
^Voet, Donald; Judith Voet; Charlotte Pratt (2008). Fundamentals of Biochemistry. John Wiley & Sons Inc. p. 508. ISBN978-0-470-12930-2.
External linksedit
UIC.edu
January 01, 1970
thiamine, pyrophosphate, this, article, needs, additional, citations, verification, please, help, improve, this, article, adding, citations, reliable, sources, unsourced, material, challenged, removed, find, sources, news, newspapers, books, scholar, jstor, se. This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Thiamine pyrophosphate news newspapers books scholar JSTOR September 2014 Learn how and when to remove this message Thiamine pyrophosphate TPP or ThPP or thiamine diphosphate ThDP or cocarboxylase 1 is a thiamine vitamin B1 derivative which is produced by the enzyme thiamine diphosphokinase Thiamine pyrophosphate is a cofactor that is present in all living systems in which it catalyzes several biochemical reactions Thiamine pyrophosphate Names IUPAC name 2 3 4 amino 2 methylpyrimidin 5 yl methyl 4 methyl 1 3 thiazol 3 ium 5 yl ethyl phosphono hydrogen phosphate Other names Thiamine diphosphate Identifiers CAS Number 136 08 3 Y 3D model JSmol Interactive image ChEBI CHEBI 9532 ChemSpider 10670483 Y KEGG C00068 MeSH Thiamine pyrophosphate PubChem CID 1132 UNII Q57971654Y Y CompTox Dashboard EPA DTXSID2048404 InChI InChI 1S C12H17N4OS ClH H4O7P2 c1 8 11 3 4 17 18 7 16 8 6 10 5 14 9 2 15 12 10 13 1 8 2 3 7 9 4 5 6 h5 7 17H 3 4 6H2 1 2H3 H2 13 14 15 1H H2 1 2 3 H2 4 5 6 q 1 p 1 YKey NBSUTVXQOGUTJX UHFFFAOYSA M YInChI 1 C12H17N4OS ClH H4O7P2 c1 8 11 3 4 17 18 7 16 8 6 10 5 14 9 2 15 12 10 13 1 8 2 3 7 9 4 5 6 h5 7 17H 3 4 6H2 1 2H3 H2 13 14 15 1H H2 1 2 3 H2 4 5 6 q 1 p 1Key NBSUTVXQOGUTJX REWHXWOFAB SMILES Cc2ncc C n 1csc CCOP O O OP O O O c1C c N n2 Properties Chemical formula C12H19N4O7P2S Molar mass 425 314382 g mol Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Thiamine pyrophosphate is synthesized in the cytosol and is required in the cytosol for the activity of transketolase and in the mitochondria for the activity of pyruvate oxoglutarate and branched chain keto acid dehydrogenases To date the yeast ThPP carrier Tpc1p the human Tpc and the Drosophila melanogaster have been identified as being responsible for the mitochondrial transport of ThPP and ThMP 2 3 4 It was first discovered as an essential nutrient vitamin in humans through its link with the peripheral nervous system disease beriberi which results from a deficiency of thiamine in the diet 5 TPP works as a coenzyme in many enzymatic reactions such as Pyruvate dehydrogenase complex 6 Pyruvate decarboxylase in ethanol fermentation Alpha ketoglutarate dehydrogenase complex Branched chain amino acid dehydrogenase complex 2 hydroxyphytanoyl CoA lyase Transketolase Contents 1 Chemistry 2 Reaction mechanisms 3 See also 4 References 5 External linksChemistry edit nbsp The ylide form of TPP Chemically TPP consists of a pyrimidine ring which is connected to a thiazole ring which is in turn connected to a pyrophosphate diphosphate functional group The part of TPP molecule that is most commonly involved in reactions is the thiazole ring which contains nitrogen and sulfur Thus the thiazole ring is the reagent portion of the molecule The C2 of this ring is capable of acting as an acid by donating its proton and forming a carbanion 7 Normally reactions that form carbanions are highly unfavorable but the positive charge on the tetravalent nitrogen just adjacent to the carbanion stabilizes the negative charge making the reaction much more favorable 7 A compound with positive and negative charges on adjacent atoms is called an ylide so sometimes the carbanion form of TPP is referred to as the ylide form 5 8 Reaction mechanisms editIn several reactions including that of pyruvate dehydrogenase alpha ketoglutarate dehydrogenase and transketolase TPP catalyses the reversible decarboxylation reaction aka cleavage of a substrate compound at a carbon carbon bond connecting a carbonyl group to an adjacent reactive group usually a carboxylic acid or an alcohol It achieves this in four basic steps The carbanion of the TPP ylid nucleophilically attacks the carbonyl group on the substrate This forms a single bond between the TPP and the substrate The target bond on the substrate is broken and its electrons are pushed towards the TPP This creates a double bond between the substrate carbon and the TPP carbon and pushes the electrons in the N C double bond in TPP entirely onto the nitrogen atom reducing it from a positive to neutral form In what is essentially the reverse of step two the electrons push back in the opposite direction forming a new bond between the substrate carbon and another atom In the case of the decarboxylases this creates a new carbon hydrogen bond In the case of transketolase this attacks a new substrate molecule to form a new carbon carbon bond In what is essentially the reverse of step one the TPP substrate bond is broken reforming the TPP ylid and the substrate carbonyl nbsp nbsp The TPP thiazolium ring can be deprotonated at C2 to become an ylid nbsp A full view of TPP The arrow indicates the acidic proton See also editTPP riboswitchReferences edit Pietrzak I 1995 Vitamin disturbances in chronic renal insufficiency I Water soluble vitamins Przegla D Lekarski in Polish 52 10 522 5 PMID 8834846 Marobbio C M T Vozza A Harding M Bisaccia F Palmieri F Walker J E 2002 11 01 Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate The EMBO Journal 21 21 5653 5661 doi 10 1093 emboj cdf583 ISSN 0261 4189 PMC 131080 PMID 12411483 Iacopetta Domenico Carrisi Chiara De Filippis Giuseppina Calcagnile Valeria M Cappello Anna R Chimento Adele Curcio Rosita Santoro Antonella Vozza Angelo 2010 03 01 The biochemical properties of the mitochondrial thiamine pyrophosphate carrier from Drosophila melanogaster FEBS Journal 277 5 1172 1181 doi 10 1111 j 1742 4658 2009 07550 x ISSN 1742 4658 PMID 20121944 Lindhurst Marjorie J Fiermonte Giuseppe Song Shiwei Struys Eduard Leonardis Francesco De Schwartzberg Pamela L Chen Amy Castegna Alessandra Verhoeven Nanda 2006 10 24 Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion embryonic lethality CNS malformations and anemia Proceedings of the National Academy of Sciences 103 43 15927 15932 Bibcode 2006PNAS 10315927L doi 10 1073 pnas 0607661103 ISSN 0027 8424 PMC 1595310 PMID 17035501 a b Pavia Donald L Gary M Lampman George S Kritz Randall G Engel 2006 Introduction to Organic Laboratory Techniques 4th Ed Thomson Brooks Cole pp 304 5 ISBN 978 0 495 28069 9 a href Template Cite book html title Template Cite book cite book a CS1 maint multiple names authors list link PDBs for Biochemistry Georgia State University Archived from the original on 2011 07 16 Retrieved 2009 02 07 a b Begley Tadhg P Ealick Steven E 2010 01 01 Liu Hung Wen Ben Mander Lew eds 7 15 Thiamin Biosynthesis Comprehensive Natural Products II Oxford Elsevier pp 547 559 doi 10 1016 b978 008045382 8 00148 9 ISBN 978 0 08 045382 8 retrieved 2020 12 16 Voet Donald Judith Voet Charlotte Pratt 2008 Fundamentals of Biochemistry John Wiley amp Sons Inc p 508 ISBN 978 0 470 12930 2 External links editUIC edu Retrieved from https en wikipedia org w index php title Thiamine pyrophosphate amp oldid 1183335083, wikipedia, wiki, book, books, library,
