Transketolase sedoheptulose phosphate metabolism

Pentose Phosphate Metabolism. The interconversion of ribose-5-phosphate and ribulose-5-phosphate is catalyzed by phosphoribo-isomerase which Axelrod et al. (20) have shown to occur in pea and spinach leaves. Axelrod and Jang (22) have purified this enzyme 380-fold from alfalfa leaves. The further transformation of ribulose 5-phosphate to xylulose-5-phosphate is catalyzed by phosphoketo-pentose epimerase, which occurs in green leaves (J. Hurwitz and B. L. Horecker, unpublished observation). Transketolase, which reversibly transforms ribose-5-phosphate and xylulose-5-phosphate to sedoheptulose-7-phosphate and glyceraldehyde-3-phosphate, and... 

The sugar metabolism is a source of many enzymes, the transketolase (TK) being one of them. TK transfers an a-hydroxy carbonyl fragment from D-xylu-lose-5-phosphate onto D-ribose-5-phosphate, forming D-sedoheptulose-7-phos-phate and D-glyceraldehyde-3-phosphate (Scheme 5.14). Since this reaction is an equilibrium reaction and starting materials and products are of similar stability, it is not very versatile for organic synthesis. Fortunately TK also accepts pyruvate instead of xylulose. Under these modified circumstances carbon dioxide... 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

The metabolism of fructose-6-P by the nonoxidative branch could in theory be initiated by transketolase, with triose phosphate as an acceptor, or by transaldolase, with erythrose-4-P as an acceptor. Dische (6) and Bonsignore et al. (7) found, however, that fructose-6-P was rapidly converted to sedoheptulose-7-P in cell extracts in the absence of added acceptor, and this observation was confirmed with a mixture of purified transaldolase and transketolase the presence of both enzymes was required 8). It appeared that each enzyme had reacted with fructose-6-P to form the acceptor for the other enz3rme, as shown in Fig. 6-2. 

Transketolase (TK) is involved in anaerobic carbohydrate metabolisms such as the nonoxidative phase of the pentose phosphate pathway. In plants and photosynthetic bacteria, TK is involved in the Calvin-Benson cycle. TK catalyses the transfer of a 2-carbon dihydroxyethyl group from a ketose phosphate (donor substrate such as D-xylulose 5-phosphate) to the Cl position of an aldose phosphate (acceptor substrate such as o-ribose 5-phosphate) (Figure 4.3) (Schneider and Lindqvist 1998). The first product is an aldose phosphate released from the donor (such as glyceraldehyde 3-phosphate) and the second is a ketose phosphate (such as sedoheptulose 7-phosphate), in which the 2-carbon fragment is attached to the acceptor. Examples of the substrates and the products mentioned above are for the first reaction of the pentose phosphate pathway. In the second reaction of the same pathway, the acceptor is D-ery-throse 4-phosphate and the second product is o-fructose 6-phosphate. A snapshot X-ray crystallographic study revealed that an ot-carbanion/enamine a,p-dihydroxyethyl ThDP is formed as a key intermediate (Fiedler et al. 2002). Then, a nucleophilic attack of the a-carbanion intermediate on the acceptor substrate occurs. 

Transaldolase. When ribose-5-phosphate is the acceptor in the transketolase reaction, the product is the 7-carbon sugar, sedoheptulose-7-phosphate. The further metabolism of this compound was found to involve another type of transfer reaction, in which a dihydroxyacetone group is shifted to a phosphoglyceraldehyde molecule. The products of this transfer are fructose-6-phosphate and a 4-carbon sugar, erythrose-4-phosphate (VI). The transfer of a dihydroxyacetone group resembles the... 

Evidence from a number of sources indicated that pentose phosphates were metabolized in a series of reactions that resulted in the formation of hexose monophosphates and hexose diphosphates. Several enzyme steps are involved in these transformations. The reaction between D-ribulose 5-phosphate and D-ribose 5-phosphate to form D-sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate is catalyzed by an enzyme known as transketolase (91). This enzyme is found in plant, animal, and bacterial cells. Thiamine pyrophosphate (TPP) and Mg ions are required as cofactors. The mechanism of the reaction was suggested (92) as shown in reaction (28). 

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