Isomerases aldose-ketose interconversions

C. A. Collyer, K. Henrick, and D. M. Blow, Mechanism for aldose-ketose interconversion by D-xylose isomerase involving ring opening followed by a 1,2-hydride shift, J.Mol.Bid. 1990, 212, 211-235. 

Many of the mechanistic aspects of glucose isomerase catalysed aldose-ketose interconversion have been under discussion for some time and are still not fully understood. By comparison with triose phosphate isomerase (TIM, EC 5.3.1.1) and glucose 6-phosphate isomerase (EC 5.3.1.9), the base-catalysed formation of an 1,2-enediol was invoked as the key step of the epimerisation based on the work of Rose and co-workers with tritium-labelled substrates [26]. An unexplained featme of the epimerisation process was that in contrast to isomerisations with triose phosphate isomerase no proton exchange with the medium could be observed with D-xylose isomerase, a fact that was attributed to the phosphate group of the former as a mediator for the exchange process [26]. Subsequently, additional important differences between triose phosphate isomerase and xylose isomerase were recognised. For example, D-xylose isomerase is appar-endy a very slow enzyme catalysing about five molecules per second per active site with an absolute requirement for divalent cations, while TIM does not need co-factors and operates at nearly 1000-fold the speed of D-xylose isomerase at... 

Figure 6 Schematic reaction mechanism of the ring-opening step in the aldose-ketose interconversion catalyzed by D-xylose isomerase ...

L-Fucose isomerase catalyzes the interconversion of L-fucose to L-fuculose and o-arabinose to D-ribulose. It has neither sequence nor structural similarity with the other aldose-ketose isomerases. A crystal structure of the E. coli enzyme with an L-fucitol bound in the active site shows that the active site is located in a 20 A deep pocket, at the bottom of which is a single Mn ion. Mn is bound to Oi and O2 of L-fucitol the side chains of a monodentate Glu-337, a bidentate Asp-361 (with long bonds to both oxygens), His-528 and a water molecule. ... 

Ketose-aldose isomerases catalyze the interconversion of aldose and ketose in sugar metabolism. Owing to their value in the sngar industry for the preparation of high-fructose... 

Sugar isomerases catalyze the interconversion between aldose and ketose. Tautomerases catalyze a keto-enol tautomerization. A-Isomerases catalyze the shift of a double bond. The reactions catalyzed by these enzymes proceed through intramolecular oxidation and reduction. 

D-Xylose isomerase catalyzes the interconversion between D-xylose and D-xylulose (Fig. 17-21). Since this enzyme acts on D-glucose to produce D-fructose, it is often referred to as glucose isomerase (Fig. 17-21). The isomerization of glucose to fructose by this enzyme is a very important process for the industrial production of high fructose com syrup. This enzyme is also applicable to the synthesis of many aldoses and ketoses because of its wide substrate specificity. The enzyme gene has been cloned from various microorganisms, and the enzyme has been overexpressed, purified, and characterized. Their three dimensional structures have also been determined I203-206. ... 

A more general access to biologically important and structurally more diverse aldose isomers makes use of ketol isomerases for the enzymatic interconversion of ketoses to aldoses. For a full realization of the concept of enzymatic stereodivergent carbohydrate synthesis, the stereochemically complementary i-rhamnose (Rhal EC 5.3.1.14) and i-fucose isomerases (Fuel EC 5.3.1.3) from E. coli have been shown to display a relaxed substrate tolerance [16,99,113,131]. Both enzymes convert sugars and their derivatives that have a common (3 J )-OH configuration, but may deviate in... 

PMI from the fungus Candida albicans is a metalloenzyme of 48.7 kDa, which catalyzes the interconversion of phosphofructose and phosphomannose. The structure of this enzyme is different from that of rabbit PGI (with an a// -fold and not a metalloenzyme) and those of the few metallo-(phospho-)ketose/aldose isomerases discussed in... 

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