チアミンピロリン酸

Thiamine pyrophosphate/ja

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
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 Y Key: NBSUTVXQOGUTJX-UHFFFAOYSA-M Y 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
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

チアミンピロリン酸（TPPまたはThPP）、またはチアミン二リン酸（ThDP）、またはコカルボキシラーゼは、酵素によって生成されるチアミン（ビタミンB₁）の誘導体である。[チアミンジホスホキナーゼ]]によって生成される。チアミン・ピロリン酸は補因子であり、すべての生体系に存在し、いくつかの生化学反応を触媒する。

チアミンピロリン酸は細胞質で合成され、細胞質ではトランスケトラーゼの活性に、ミトコンドリアではピルビン酸、オキソグルタル酸、分岐鎖ケト酸デヒドロゲナーゼの活性に必要である。現在までに、ThPPとThMPのミトコンドリア輸送を担うものとして、酵母ThPPキャリアー（Tpc1p）、ヒトTpc、ショウジョウバエが同定されている。ThPPは、食事療法におけるチアミンの欠乏に起因する末梢神経系の病気脚気との関連性から、ヒトの必須栄養素（ビタミン）として初めて発見された。

TPPは多くの酵素反応において補酵素として働く：

• ピルビン酸デヒドロゲナーゼ複合体
• エタノール発酵におけるピルビン酸脱炭酸酵素
• α-ケトグルタル酸デヒドロゲナーゼ複合体
• 分岐鎖アミノ酸デヒドロゲナーゼ複合体
• 2-ヒドロキシフィタノイル-CoAリアーゼ
• トランスケトラーゼ

化学

TPPの「イリド型」

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 much more favorable. 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".

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:

1. 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.)
2. 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.
3. 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.)
4. 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.

See also

• TPP riboswitch

External links

• UIC.edu