Pentose Phosphate Pathway of Glucose Oxidation:- The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate
In tissues that require primarily NADPH, the pentose phosphates produced in the oxidative phase of the path way are recycled into glucose 6-phosphate. In this non oxidative phase, ribulose 5-phosphate is first epimerized to xylulose 5-phosphate:
Then, in a series of rearrangements of the carbon skeletons (Fig. 14–22), six five-carbon sugar phosphates are converted to five six-carbon sugar phosphates, completing the cycle and allowing continued oxidation of glucose 6-phosphate with production of NADPH. Continued recycling leads ultimately to the conversion of glucose 6-phosphate to six CO2. Two enzymes unique to the pentose phosphate pathway act in these interconversions of sugars: transketolase and transaldolase. Transketolase catalyzes the transfer of a two-carbon fragment from a ketose donor to an aldose acceptor (Fig. 14–23a). In its first appearance in the pentose phosphate pathway, transketolase transfers C-1 and C-2 of xylulose 5-phosphate to ribose 5-phosphate, forming the seven-carbon product sedoheptulose 7-phosphate (Fig. 14–23b). The remaining three-carbon fragment from xylulose is glyceraldehyde 3-phosphate. Next, transaldolase catalyzes a reaction similar to the aldolase reaction of glycolysis: a three-carbon frag ment is removed from sedoheptulose 7-phosphate and condensed with glyceraldehyde 3-phosphate, forming fructose 6-phosphate and the tetrose erythrose 4-phosphate (Fig. 14–24). Now transketolase acts again, forming fructose 6-phosphate and glyceraldehyde 3-phosphate from erythrose 4-phosphate and xylulose 5-phosphate (Fig. 14–25). Two molecules of glyceraldehyde 3-phosphate formed by two iterations of these reactions can be converted to a molecule of fructose 1,6-bisphosphate as in gluconeogenesis (Fig. 14–16), and finally FBPase-1 and phosphohexose isomerase convert fructose 1,6-bisphosphate to glucose 6-phosphate. The cycle is complete: six pentose phosphates have been converted to five hexose phosphates (Fig. 14–22b).
FIGURE 14–22 Nonoxidative reactions of the pentose phosphate pathway. (a) These reactions convert pentose phosphates to hexose phosphates, allowing the oxidative reactions (see Fig. 14–21) to continue. The enzymes transketolase and transaldolase are specific to this pathway; the other enzymes also serve in the glycolytic or gluconeogenic pathways. (b) A schematic diagram showing the pathway from six pentoses (5C) to five hexoses (6C). Note that this involves two sets of the interconversions shown in (a). Every reaction shown here is reversible; unidirectional arrows are used only to make clear the direction of the reactions during continuous oxidation of glucose 6 phosphate. In the light-independent reactions of photosynthesis, the direction of these reactions is reversed (see Fig. 20–10).
FIGURE 14–23 The first reaction catalyzed by transketolase. (a)The general reaction catalyzed by trans ketolase is the transfer of a twocarbon group, carried temporarily on enzyme-bound TPP, from a ketose donor to an aldose acceptor. (b)Conversion of two pentose phosphates to a triose phosphate and a seven-carbon sugar phosphate, sedoheptulose 7-phosphate.
FIGURE 14–24 The reaction catalyzed by transaldolase.
FIGURE 14–25 The second reaction catalyzed by transketolase.
FIGURE 14–26 Carbanion intermediates stabilized by covalent in teractions with transketolase and transaldolase. (a) The ring of TPP stabilizes the two-carbon carbanion carried by transketolase; see Fig. 14–13 for the chemistry of TPP action. (b) In the transaldolase reaction, the protonated Schiff base formed between the -amino group of a Lys side chain and the substrate stabilizes a three-carbon carbanion.
Transketolase requires the cofactor thiamine py rophosphate (TPP), which stabilizes a two-carbon carbanion in this reaction (Fig. 14–26a), just as it does in the pyruvate decarboxylase reaction (Fig. 14–13). Transaldolase uses a Lys side chain to form a Schiff base with the carbonyl group of its substrate, a ketose, thereby stabilizing a carbanion (Fig. 14–26b) that is central to the reaction mechanism. The process described in Figure 14–21 is known as the oxidative pentose phosphate pathway. The first two steps are oxidations with large, negative standard free-energy changes and are essentially irreversible in the cell. The reactions of the nonoxidative part of the pentose phosphate pathway (Fig. 14–22) are readily reversible and thus also provide a means of converting hexose phosphates to pentose phosphates. As we shall see in Chapter 20, a process that converts hexose phosphates to pentose phosphates is crucial to the photo synthetic assimilation of CO2 by plants. That pathway, the reductive pentose phosphate pathway, is essentially the reversal of the reactions shown in Figure 14–22 and employs many of the same enzymes. All the enzymes in the pentose phosphate pathway are located in the cytosol, like those of glycolysis and most of those of gluconeogenesis. In fact, these three pathways are connected through several shared inter mediates and enzymes. The glyceraldehyde 3-phosphate formed by the action of transketolase is readily converted to dihydroxyacetone phosphate by the glycolytic enzyme triose phosphate isomerase, and these two trioses can be joined by the aldolase as in gluconeogenesis, forming fructose 1,6-bisphosphate. Alternatively, the triose phosphates can be oxidized to pyruvate by the glycolytic reactions. The fate of the trioses is determined by the cell’s relative needs for pentose phosphates, NADPH, and ATP.
