Thiamin diphosphate:  a mechanistic update on enzymic and nonenzymic catalysis of decarboxylation

Kluger, Ronald

doi:10.1021/cr00081a001

Cited by 254 publications

(162 citation statements)

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“…A reaction mechanism for the decarboxylation has been proposed for PDC (Kluger, 1987) and BFD (Weiss et al, 1988;Reynolds et al, 1988;Iding et al, 2000). According to these investigations, the reaction is catalyzed directly at the cofactor ThDP with an enaminecarbanion as intermediate.…”

Section: Comparison Of Computer Programsmentioning

confidence: 99%

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Zavrel

Schmidt

Michalik

et al. 2007

Journal of Biotechnology

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Section: Comparison Of Computer Programsmentioning

confidence: 99%

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Zavrel

Schmidt

Michalik

et al. 2007

Journal of Biotechnology

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“…Several reviews have discussed the catalytic function of ThDP [38,80,136,142,169]. In all ThDP-dependent enzymes the abstraction of the proton from the C2 atom is the ®rst step in catalysis, which is followed by a nucleophilic attack of this carbanion on the substrate.…”

Section: Transketolase: a Thiamin Diphosphate Dependent Enzymementioning

confidence: 99%

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

223

164

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This review highlights recent research on the properties and functions of the enzyme transketolase, which requires thiamin diphosphate and a divalent metal ion for its activity. The transketolase-catalysed reaction is part of the pentose phosphate pathway, where transketolase appears to control the non-oxidative branch of this pathway, although the overall¯ux of labelled substrates remains controversial. Yeast transketolase is one of several thiamin diphosphate dependent enzymes whose three-dimensional structures have been determined. Together with mutational analysis these structural data have led to detailed understanding of thiamin diphosphate catalysed reactions. In the homodimer transketolase the two catalytic sites, where dihydroxyethyl groups are transferred from ketose donors to aldose acceptors, are formed at the interface between the two subunits, where the thiazole and pyrimidine rings of thiamin diphosphate are bound. Transketolase is ubiquitous and more than 30 full-length sequences are known. The encoded protein sequences contain two motifs of high homology; one common to all thiamin diphosphate-dependent enzymes and the other a unique transketolase motif. All characterised transketolases have similar kinetic and physical properties, but the mammalian enzymes are more selective in substrate utilisation than the nonmammalian representatives. Since products of the transketolase-catalysed reaction serve as precursors for a number of synthetic compounds this enzyme has been exploited for industrial applications. Putative mutant forms of transketolase, once believed to predispose to disease, have not stood up to scrutiny. However, a modi®cation of transketolase is a marker for Alzheimer's disease, and transketolase activity in erythrocytes is a measure of thiamin nutrition. The cornea contains a particularly high transketolase concentration, consistent with the proposal that pentose phosphate pathway activity has a role in the removal of light-generated radicals. #

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“…Enzymatic thiamin catalysis proceeds through two carbanion intermediates, the ylide of ThDP, formed after abstraction of the C2 proton of the thiazolium ring, and the 2-␣ carbanion, formed after nucleophilic attack of the C2 carbon on the substrate (1)(2)(3)(4). It is thought that the ␣-carbanion intermediate is stabilized via the thiazolium ring of ThDP, which acts as an electron sink.…”

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confidence: 99%

“…The ␣-carbanion͞enamine intermediate is of central importance in thiamin catalysis because, depending on the nature of its substituent at the ␣-carbon atom, a variety of enzymatic functions can be derived. Accordingly, the fate of this intermediate differs in the various ThDP-dependent enzymes; for instance, in pyruvate decarboxylase, the ␣-carbanion will be protonated at the ␣-carbon position, leading to the expulsion of the product, acetaldehyde (2,4). In the transketolase (TK) reaction, the carbanion reacts with an acceptor substrate, and the product, a ketose with the carbon chain extended by two carbon atoms, will be released (3,5).…”

mentioning

confidence: 99%

Snapshot of a key intermediate in enzymatic thiamin catalysis: Crystal structure of the α-carbanion of (α,β-dihydroxyethyl)-thiamin diphosphate in the active site of transketolase from Saccharomyces cerevisiae

Fiedler

Thorell

Sandalova

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

125

141

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Thiamin diphosphate: a mechanistic update on enzymic and nonenzymic catalysis of decarboxylation

Cited by 254 publications

References 34 publications

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Snapshot of a key intermediate in enzymatic thiamin catalysis: Crystal structure of the α-carbanion of (α,β-dihydroxyethyl)-thiamin diphosphate in the active site of transketolase from Saccharomyces cerevisiae

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