Free energy triose phosphate isomerase

Triose phosphate isomerase catalyzes the conversion of dihy-droxyacetone-P to glyceraldehyde-3-P. The standard free energy change, AG°, for this reaction is +7.6 kj/mol. However, the observed free energy change (AG) for this reaction in erythrocytes is +2.4 kj/mol. 

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.

Triose phosphate isomerase was the subject of a series of elegant and comprehensive isotope exchange experiments, which led to the establishment of the complete free energy profile for the catalysed reaction. In the following discussion, glyceraldehyde 3-phosphate will be abbreviated to G3P, dihydroxyacetone phosphate to DHAP and the enediolate to INT. The enzyme complexes and transition states will be denoted as in Figure 6.7. Reference to one of... 

Free energy profile for the action of rabbit muscle triose phosphate isomerase. The profile is drawn approximately to scale the exchanged hydron is shown in bold and the barrier to hydron exchange as a dotted line. Other dotted lines are upper or lower limits. 

As first espoused by Knowles and Albery, the limiting selective pressure on enzymatic function is the diffusion-controlled limit by which substrates bind and products dissociate [7]. In the case of triose phosphate isomerase [8], ketosteroid iso-merase [9], mandelate racemase [10], and proline racemase [11], the energies of various transition states on the reactions coordinates have been quantitated, with the result that the free energies of the transition states for the proton transfer reactions to and from carbon are competitive with those for substrate association/ product dissociation. However, as discussed in later sections, the energies of the... 

W. Albery and J. Knowles, Biochemistry, 25, 5627 (1976). Free-Energy Profile for the Reaction Catalysed by Triose Phosphate Isomerase. 

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