Properties and functions of the thiamin diphosphate dependent enzyme transketolase

This review highlights recent research on the properties and functions of t he 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 flux of labelled substrates remains controversial. Yeast transketolase is one of several th iamin diphosphate dependent enzymes whose three-dimensional structures have been determined. Together with mutational analysis these structural data h ave led to detailed understanding of thiamin diphosphate catalysed reaction s. In the homodimer transketolase the two catalytic sites, where dihydroxye thyl groups are transferred from ketose donors to aldose accepters, are for med at the interface between the two subunits, where the thiazole and pyrim idine rings of thiamin diphosphate are bound. Transketolase is ubiquitous a nd more than 30 full-length sequences are known. The encoded protein sequen ces contain two motifs of high homology; one common to all thiamin diphosph ate-dependent enzymes and the other a unique transketolase motif. All chara cterised transketolases have similar kinetic and physical properties, but t he mammalian enzymes are more selective in substrate utilisation than the n onmammalian representatives. Since products of the transketolase-catalysed reaction serve as precursors for a number of synthetic compounds this enzym e 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 modification of transketolase is a marker for Alzheim er's disease, and transketolase activity in erythrocytes is a measure of th iamin nutrition. The cornea contains a particularly high transketolase conc entration, consistent with the proposal that pentose phosphate pathway acti vity has a role in the removal of light-generated radicals. (C) 1998 Elsevi er Science Ltd. All rights reserved.