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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/02 13:19:35」(JST)

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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. 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.^[2]

TPP works as a coenzyme in many enzymatic reactions, such as:

Pyruvate dehydrogenase complex^[3]
Pyruvate decarboxylase in ethanol fermentation
Alpha-ketoglutarate dehydrogenase complex
Branched-chain amino acid dehydrogenase complex
2-hydroxyphytanoyl-CoA lyase
Transketolase

Chemistry

The "ylid 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. 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 more favorable. (A compound with positive and negative charges on adjacent atoms is called an ylid or ylide, so sometimes the carbanion form of TPP is referred to as the "ylid form".^[2]^[4]

Reaction mechanisms

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.

References

^ Pietrzak I (1995). "[Vitamin disturbances in chronic renal insufficiency. I. Water soluble vitamins]". Przegla̧D Lekarski (in Polish) 52 (10): 522–5. PMID 8834846. |accessdate= requires |url= (help)
^ ^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.
^ "PDBs for Biochemistry". Georgia State University. Retrieved 2009-02-07.
^ Voet, Donald; Judith Voet; Charlotte Pratt (2008). Fundamentals of Biochemistry. John Wiley & Sons Inc. p. 508. ISBN 978-0-470-12930-2.

External links

UIC.edu

UpToDate Contents

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English Journal

A novel ultrasensitive phosphate amperometric nanobiosensor based on the integration of pyruvate oxidase with highly ordered gold nanowires array.

Ogabiela E1, Adeloju SB2, Cui J3, Wu Y3, Chen W4.
Biosensors & bioelectronics.Biosens Bioelectron.2015 Sep 15;71:278-85. doi: 10.1016/j.bios.2015.04.026. Epub 2015 Apr 14.
A novel phosphate amperometric nanobiosensor, based on an intimate integration of pyruvate oxidase (PyOx) and its cofactors, thiamine pyrophosphate (TPP) and flavin adenine dinucleotide (FAD), with a highly ordered gold nanowires array (AuNWA) has been developed. The successful integration of PyOx a
PMID 25913449

The effect of thiamine pyrophosphate on ethambutol-induced ocular toxicity.

Cinici E1, Cetin N, Ahiskali I, Suleyman B, Altuner D, Alp HH, Sener E, Calik I, Suleyman H.
Cutaneous and ocular toxicology.Cutan Ocul Toxicol.2015 Sep 4:1-6. [Epub ahead of print]
CONTEXT: Ethambutol-induced retinal oxidative damage in patients with tuberculosis is still not being adequately treated. The protective effect of thiamine pyrophosphate against oxidative damage in some tissues has been reported, but no information on the protective effects of thiamine pyrophosphate
PMID 26339826

Identification of the Final Two Genes Functioning in Methanofuran Biosynthesis in Methanocaldococcus jannaschii.

Wang Y1, Xu H1, Jones MK1, White RH2.
Journal of bacteriology.J Bacteriol.2015 Sep 1;197(17):2850-8. doi: 10.1128/JB.00401-15. Epub 2015 Jun 22.
All methanofuran structural variants contain a basic core structure of 4-[N-(γ-l-glutamyl)-p-(β-aminoethyl)phenoxymethyl]-(aminomethyl)furan (APMF-Glu) but have different side chains depending on the source organism. Recently, we identified four genes (MfnA, MfnB, MfnC, and MfnD) that are responsi
PMID 26100040

Japanese Journal

Whole blood concentration of thiamine diphosphate requires correction for red blood cell count in the nutritional assessment of thiamine status

生物試料分析 = Journal of analytical bio-science 34(3), 218-222, 2011
NAID 40019884141

Characterization of Acetohydroxyacid Synthase I from Escherichia coli K-12 and Identification of Its Inhibitors

Bioscience, biotechnology, and biochemistry 74(11), 2281-2286, 2010-11-23
NAID 10027561651

不斉 Stetter 反応の最近の進歩

有機合成化学協会誌 : JOURNAL OF Synthetic Organic Chemistry JAPAN 65(9), 905-906, 2007-09-01
NAID 10019753245

「コカルボキシラーゼ」

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 Registry Number	154-87-0
ChemSpider	10670483
	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 ; Key: NBSUTVXQOGUTJX-UHFFFAOYSA-M ; InChI=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-1; Key: NBSUTVXQOGUTJX-REWHXWOFAB ;
Jmol-3D images	Image
MeSH	Thiamine+pyrophosphate
PubChem	1132
	SMILES [Cl-].OP(=O)(O)OP(O)(O)=O.Cc2nc(N)c(C[n+]1csc(CCO)c1C)cn2 ;
UNII	Q57971654Y
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).
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	Infobox references