Triose phosphate isomerase, function

N6. Neubauer, B. A., Pekrun, A., Eber, S. W Lakomek, M and Schroter, W., Relation between genetic defect, altered protein structure, and enzyme function in triose-phosphate isomerase (TPI) deficiency. Eur. J. Pediatr. 151,232a (1992). 

A quantitative expression developed by Albery and Knowles to describe the effectiveness of a catalyst in accelerating a chemical reaction. The function, which depends on magnitude of the rate constants describing individual steps in the reaction, reaches a limiting value of unity when the reaction rate is controlled by diffusion. For the interconversion of dihydroxacetone phosphate and glyceraldehyde 3-phosphate, the efficiency function equals 2.5 x 10 for a simple carboxylate catalyst in a nonenzymic process and 0.6 for the enzyme-catalyzed process. Albery and Knowles suggest that evolution has produced a nearly perfect catalyst in the form of triose-phosphate isomerase. See Reaction Coordinate Diagram... 

There are numerous cases of proteins for which structures have been determined in more than one state of ligation. In some cases, the structures undergo little change, except perhaps for specific and localized changes associated with particular functional residues—for example, triose phosphate isomerase. Other cases, such as... 

Enzyme Mechanisms.— Triose phosphate isomerase has been a popular enzyme recently, having been the chief example quoted in two reviews on perfection and efficiency in enzyme catalysis - and the subject of seven successive papers in one issue of Biochemistry including one on the evolution of enzyme function and the development of catalytic efficiency. During glycolysis in muscle, fructose 1,6-bisphos-... 

However, (26) should bind strongly to class II aldolases on account of its chelating ability and this has been found to be the case with rabbit muscle fructose diphosphate aldolase where (26) functions as a competitive inhibitor. Triose phosphate isomerase is also strongly inhibited by (26) this may be due to its similarity to the cw-eriediolate (28), which is an intermediate in the reaction pathway of this enzyme. Acyldihydroxyacetone phosphates are important intermediates in the biosynthesis of glycerolipids and the acyl... 

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... 

D. Pompliano, A. Peyman, and J. Knowles, Biochemistry, 29,3186 (1990). Stabilization of a Reaction Intermediate as a Catalytic Device Definition of the Functional Role of the Flexible Loop in Triose Phosphate Isomerase. 

Figure 8.49 Mechanisms of three enzymes that utilise general acid-base catalysis as part of their mechanistic paths to successful bio-catalysis, (a) triose phosphate isomerase (TIM), (b) lysozyme, (c) RNAse A. In all cases substrates are shown in red. Lone pair donor amino acid residues are general bases, lone pair acceptor amino acid residues are general acids. Note that pK (a commonly used term) is the equivalent of p/f/ or pK (as written in this text book) as appropriate for an acidic or basic functional group.

Isomerization of functional groups. In many biochemical reactions, the position of a functional group is changed within a molecule, but the molecule itself contains the same number and kind of atoms that it did in the begiiming. In other words, the substrate and product of the reaction are isomers. The iso-merases (for example, triose phosphate isomerase, shown following), carry out these rearrangements. 

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

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