Thiamine pyrophosphate

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Thiamine pyrophosphate
2D structure for Thiamine pyrophosphate
Chemical Name	2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate
Chemical Formula	C₁₂H₁₉N₄O₇P₂S
CAS Number	154-87-0
Chemical Information	HMDB01372
Biochemical Taxonomy	Misc
Functional Taxonomy	Not Available
Nutritional Taxonomy	Not Available
Metabolic Pathways	Butanoate Metabolism Glycolysis Lysine Degradation Pyruvate Metabolism Valine, Leucine and Isoleucine Biosynthesis Valine, Leucine and Isoleucine Degradation
Biofluid Location	Blood Cerebrospinal Fluid (CSF)
Tissue Location	Erythrocyte Fibroblasts Brain
Normal Biofluid Concentrations	Blood: 0.095 - 0.155 uM Cerebrospinal Fluid (CSF): 0.0032 +/- 0.0022 uM
Normal Tissue Concentrations	Not Available
Diseases / Conditions Related to Nutrition	Alzheimer's disease In patients diagnosed with clinical obvious cerebrocortical necrosis
Other (Monogenic Disorders)	Not Available
Abnormal Biofluid Concentrations	Blood (In patients diagnosed with clinical obvious cerebrocortical necrosis): 0.034 (0 - 0.066) uM Cerebrospinal Fluid (CSF) (Alzheimer's disease): 0.0025 +/- 0.0017 uM
Abnormal Tissue Concentrations	Not Available
Physiological Processes	Not Available

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Introduction

guidelines
Thiamine pyrophosphate is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. The enzymes are important in the biosynthesis of a number of cell constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses and in biosyntheses and for synthesis of pentoses used as nucleic acid precursors. The chemical structure of TPP is that of an aromatic methylaminopyrimidine ring, linked via a methylene bridge to a methylthiazolium ring with a pyrophosphate group attached to a hydroxyethyl side chain. In non-enzymatic model studies it has been demonstrated that the thiazolium ring can catalyse reactions which are similar to those of TPP-dependent enzymes but several orders of magnitude slower. Using infrared and NMR spectrophotometry it has been shown that the dissociation of the proton from C2 of the thiazolium ring is necessary for catalysis; the abstraction of the proton leads to the formation of a carbanion (ylid) with the potential for a nucleophilic attack on the carbonyl group of the substrate. In all TPP-dependent enzymes the abstraction of the proton from the C2 atom is the first step in catalysis, which is followed by a nucleophilic attack of this carbanion on the substrate. Subsequent cleavage of a C-C bond releases the first product with formation of a second carbanion (2-greek small letter alpha-carbanion or enamine). The formation of this 2-greek small letter alpha-carbanion is the second feature of TPP catalysis common to all TPP-dependent enzymes. Depending on the enzyme and the substrate(s), the reaction intermediates and products differ. Methyl-branched fatty acids, as phytanic acid, undergo peroxisomal beta-oxidation in which they are shortened by 1 carbon atom. This process includes four steps: activation, 2-hydroxylation, thiamine pyrophosphate dependent cleavage and aldehyde dehydrogenation. In the third step, 2-hydroxy-3-methylacyl-CoA is cleaved in the peroxisomal matrix by 2-hydroxyphytanoyl-CoA lyase (2-HPCL), which uses thiamine pyrophosphate (TPP) as cofactor. The thiamine pyrophosphate dependence of the third step is unique in peroxisomal mammalian enzymology. Human pathology due to a deficient alpha-oxidation is mostly linked to mutations in the gene coding for the second enzyme of the sequence, phytanoyl-CoA hydroxylase (EC 1.14.11.18). (PMID: 12694175, 11899071, 9924800)