Triose enediol intermediate

Figure 2. Free energy profile for converting di hydroxy acetone phosphate, the substrate (abbreviated S) and glyceraldehyde 3-phosphate, the product (abbreviated P), with intermediate formation of the enedi-olate (abbreviated Z). Catalysis occurs either by a free carboxyl group (levels connected by dotted lines) or by triose-phosphate isomerase (levels connected by dashed lines). The vertical arrows show the limits of those states that are less well defined as a result of uncertainty in the experimental data. The transition state marked "e" refers to the exchange of protons between the solvent and the enzyme-bound enediol intermediate (EZ). Reproduced with permission of the authors and the American Chemical Society.

Fig. 3 Mechanism of triose-P isomerase.4 Note the isoenergetic shift of the histidine between the two OH groups of the enediolate intermediate a low-barrier hydrogen bond is present in both structures.

Much is known about the catalytic mechanism of triose phosphate isomerase. TIM catalyzes the transfer of a hydrogen atom from carbon 1 to carbon 2 in converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, an intramolecular oxidation-reduction. This isomerization of a ketose into an aldose proceeds through an enediol intermediate (Figure 16.6). 

Figure 16.5 Catalytic mechanism of triose phosphate isomerase. (1) Glutamate 165 acts as a general base by abstracting a proton (H ) from carbon 1. Histidine 95, acting as a general acid, donates a proton to the oxyger atom bonded to carbon 2, forming the enediol intermediate,...

Monosaccharides can exist as aldehydes or ketones and are called aldoses or ketoses, respectively. For example, (Figure 9.3) shows the structures of glyceraldehyde, an aldo-triose, and dihydroxyacetone, a keto-triose. Glyceraldehyde and dihydroxyacetone have the same atomic composition, but differ only in the position of the hydrogens and double bonds. Moreover, they can interconvert via an enediol intermediate (Figure 9.4). When the structures of molecules are related in these ways, the molecules are called tautomers. 

The reaction is similar to the hexose phosphate isomerase and triose phosphate isomerase reactions of glycolysis and probably proceeds through an enediol intermediate ... 

This interconversion of triose phosphates occurs by the same type of keto-enol tautomer-ism (Section 12.8A) and enediol intermediate we have already seen in the isomerization of D-glucose 6-phosphate to D-fructose 6-phosphate. Note that D-glyceraldehyde 3-phosphate is chiral and that two enantiomers are possible for it. The enzyme catalyzing this reaction has a high stereospecificity, and only the D enantiomer is formed. 

Because dihydroxyacetone phosphate and glyceraldehyde 3-phosphate enolize to give a common intermediate, they exist in equilibrium. The enzyme triose phosphate isomerase efficiently catalyzes the isomerization. Although the enediol intermediate is chiral, the enzyme forms only the i enantiomer of glyceraldehyde 3 phosphate. In aqueous solution, an acid-catalyzed reaction would yield a racemic mixture of aldehyde 3-phosphate. 

The oxidation of aldoses and sugar phosphates by Cr(VI) has been reviewed (23 refs.). The kinetic behaviour and the relative reactivities of several trioses, tetioses, pentoses and hexoses, amino sugars, and methylated sugars towards potassium permanganate in perchloric acid solution have been examined. Mechanisms have been proposed for the oxidation of arabinose and xylose by iodine in alkaline solution and by alkaline NBS under Ru(Vni)-catalysis. For the oxidation of monosaccharides by sodium iV-bromobenzenesulfonamide in alkaline media, reaction via 1,2-enediol intermediates has been postulated. 1 1 Stoichiometry has been observed in the oxidation of D-fructose with PCC. ... 

Triose phosphate isomerase is one of the enzymes of glycolysis (see Section 15.2) and is responsible for converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate by a two-stage enolization process. An intermediate enediol is involved - this common enol can revert to a keto form in two ways, thus providing the means of isomerization. 

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