Isomerases hydride shift mechanism

Fig. 2.2.S.3 Structure of rhamnose isomerase, and proposed hydride-shift mechanism for the ketol isomerization.

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. 

This hydride shift reaction mechanism is quite different from the base-catalyzed enolization mechanism proposed for phospho sugar isomerases such as triosephos-phate isomerase which generally do not require a metal ion for activity12261. 

Figure 17-22. Reaction mechanism for xylose-xylulose conversion by D-xylose isomerase through ring opening (A) and hydride shift (B). Reprinted from Fuxreiter et al.[225. ...

The enzyme D-xylose isomerase catalyzes the interconversion of D-xylose to E>-xylulose and D-glucose to D-fhictose by transferring a hydrogen atom between Cl and C2. Various mechanisms have been suggested including base-catalyzed transfer of a proton with a cis-ene diol as an intermediate, a hydride transfer, and a metal-assisted hydride shift [86-89]. The last of these three suggestions is the preferred mechanism at this time, but more studies of the mechanism are needed. 

Another interesting example of the isoracemisation mechanism is in the triose phosphate isomerase pathway. Rieder and Rose [47] indicated that exchange of the proton in the triose phosphate occurred in the presence of the isomerase not consistent with the hydride shift. Later work by Herhhy et al. [48] indicated that some 3-6% of the hydrogen at C, of the product dihydroxyacetone phosphate was transferred to Cj (Eqn. 66). 

Figure 39 The reaction catalyzed by the enzyme D-xylose isomerase (a) formulae of reactants and products and (b) postulated mechanisms of action via a hydride shift or an ene diol intermediate. The former does not require an active site group but the latter requires an active site base to abstract a hydrogen ion and transfer it to the adjacent carbon atom...

An enzymic counterpart of these complex base-catalysed rearrangements of sugars may be the reaction catalysed by 4-phospho-3,4-dihydroxy-2-butanone synthetase. The enzyme catalyses the formation of the eponymous intermediate in secondary metabolism from ribulose 5-phosphate. Labelling studies indicated that C1-C3 of the substrate became C1-C3 of the product, that H3 of the substrate derived from solvent and that C4 was lost as formate. X-ray crystal structures of the native enzyme and a partly active mutant in complex with the substrate are available. The active site of the enzyme from Met ha-nococcus jannaschii contains two metals, which can be any divalent cations of the approximate radius of Mg " or Mn ", the two usually observed. Their disposition is very reminiscent of those in the hydride transfer aldose-ketose isomerases, but also to ribulose-5-phosphate carboxylase, which works by an enolisation mechanism, so the enolisation route suggested by Steinbacher et al. is repeated in Figure 6.14, as is the Bilik-type alkyl group shift, for which an equivalent reverse aldol-aldol mechanism cannot be written. 

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