Triose-P isomerase

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.

Phosphofructokinase, the enzyme that phosphory-lates fructose-1-phosphate to yield the diphosphate, the precursor of the triose phosphates, has a fate similar to that of hexokinase, except that its prenatal activity is only three times greater than that of adult liver, and the prenatal activity drops to adult values within 9 days after birth. Fructose-1,6-diphosphate, triose-P-isomerase, and glyceraldehyde phosphate dehydrogenase all have high fetal activities that slightly increase at the adult levels in the newborn. Thus, in the fetal liver the activity of these enzymes seems to favor the formation rather than the use of lactic acid. 

Anderson, L.E. and Carol, A.A. (2005) Enzyme co-localization in the pea leaf cytosol 3-P-glycerate kinase, glyceraldehyde-3-P dehydrogenase, triose-P isomerase and aldolase. Plant Sci 169, 620-628... 

Figure 2.20 Motifs that are adjacent in the amino acid sequence are also usually adjacent in the three-dimensional structure. Triose-phosphate isomerase is built up from four P-a-p-a motifs that are consecutive both in the amino acid sequence (a) and in the three-dimensional structure (b).

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 5-6. Examples of tertiary structure of proteins. Top The enzyme triose phosphate isomerase. Note the elegant and symmetrical arrangement of alternating p sheets and a helices. (Courtesy of J Richardson.) Bottom Two-domain structure of the subunit of a homodimeric enzyme, a bacterial class II HMG-CoA reductase. As indicated by the numbered residues, the single polypeptide begins in the large domain, enters the small domain, and ends in the large domain. (Courtesy ofC Lawrence, V Rod well, and C Stauffacher, Purdue University.)...

Figure 4.9 (a) Triose phosphate isomerase (TIM), has a (3-a-(3 structure made up of eight P-a motifs terminating in a final a-helix, which form a barrel-like structure, (b) An open twisted P-sheet with helices on both sides, such as the coenzyme-binding domain of many dehydrogenases. (From Branden and Tooze, 1991. Reproduced by permission of Garland Publishing, Inc.)... 

In each of the three divisions of life, the most common fold is the P-loop NTPase. Four common folds, namely P-loop NTPases, Triose Phosphate Isomerase (TIM) barrels, ferredoxin-like domains, and Rossmann-fold domains, are see in the top-10 lists for all three divisions (Table IV). 

The natural substrate for the dehydrogenase, glyceraldehyde-3-phosphate (G-3-P), had been synthesized earlier by Hermann Fischer, Emil Fischer s son, and Baer in 1932. In 1934 Meyerhof and Lohmann synthesized hexose diphosphate, establishing it to be fructose 1,6 bisphosphate (F-l, 6 bis P). With F-1,6 bisP as substrate and hydrazine to trap the aldehydic and ketonic products of the reaction, G-3-P was identified in the mixture of G-3-P and dihydroxyacetone phosphate which resulted. Triose phosphate isomerase was then isolated and the importance of phosphorylated 3C derivatives established. 

Figure 3. Model of (p a)s TIM barrel from triose phosphate isomerase. Numbered arrow and twisted ribbon structures are beta sheets and alpha helicies, respectively. (Adapted and reproduced from Ref. 66 with permission. Cop3night 1984 American Association for the Advancement of Science.)...

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.

Petsko, G. A., Phillips, D. C., Williams, R. J. P. and Wilson, I. A. (1978). On the protein crystal chemistry of chloroplatinite ions general principles and interactions with triose phosphate isomerase. /. Mol. Biol. 120, 345-359. 

The eight-stranded P cylinder of plastocyanin (Fig. 2-16A) is somewhat flattened and can also be regarded as a P sandwich.116118 However, the P barrel of triose phosphate isomerase (see Fig. 2-28) is surrounded by eight a helices which provide additional stability and a high symmetry. Bacterial outer membranes contain pores created by very large P cylinders within proteins called porins.119120 Tire one shown in Fig. 8-20 has 16 strands. 

Fructose bisphosphate is cleaved by action of an aldolase (reaction 4) to give glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. These two triose phosphates are then equilibrated by triose phosphate isomerase (reaction 5 see also Chapter 13). As a result, both halves of the hexose can be metabolized further via glyceraldehyde 3-P to pyruvate. The oxidation of glyceraldehyde 3-P to the corresponding carboxylic acid, 3-phosphoglyceric acid (Fig. 17-7, reactions 6 and 7), is coupled to synthesis of a molecule of ATP from ADP and P . This means that two molecules of ATP are formed per hexose cleaved, and that two molecules of NAD+ are converted to NADH in the process. 

Figure 16.5. Structure of Triose Phosphate Isomerase. This enzyme consists of a central core of eight parallel P...

Figure 6.2(a) Illustration of the so-called a/p barrel structure for triose phosphate isomerase after [1]. The parallel P-sheet chains are drawn in red and they form a catenoid. Outside the catenoid there are eight a-helices (green). (Adapted from [1].)... 

P barrel The folding of a polypeptide chain to form a barrel-shaped structure with eight p strands as the lining. Eight a helices lie outside this p sheet. Both the a helices and the P strands follow a right-handed spiral around the axis of the barrel. The amino acid sequence in such a protein is such that p sheet and a helix alternate to give Pa)s- This motif was first seen in triose phosphate isomerase, and has since been observed in many other protein structures. 

Figure 2-28 The eight-fold a/p barrel structure of triose phosphate isomerase. From Richardson. (A) Stereoscopic view. (B) Ribbon drawing. Courtesy of Jane Richardson." ...

Figure 13-6 Stereoscopic view into the active site of triose phosphate isomerase showing side chains of some charged residues PGH, a molecule of bormd phosphoglycolohydroxamate, an analog of the substrate enolate. The peptide backbone, as an alpha-carbon plot, is shown in light lines. The (a / P)g-barrel structure is often called a TIM barrel because of its discovery in this enzyme. Courtesy of M. Karplus.

A one-pot procedure has been proposed to convert dihydroxyacetone and phosphorenol pyruvate (PEP) into D-tagatose 1,6-diphosphate 6 (O Scheme 9). The reaction mixture contains glycerolkinase, p)TUvate kinase, triose phosphate isomerase, and a D-tagatose 1,6-diphosphate aldolase [81],... 

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