The pentose phosphate pathway meets the need of all organisms for a source of NADPH to use in reductive biosynthesis. This pathway consists of two phases: the oxidative generation of NADPH and the nonoxidative interconversion of sugars (Figure 20.19). In the oxidative phase, NADPH is generated when glucose 6-phosphate is oxidized to ribose 5-phosphate. This five-carbon sugar and its derivatives are components of RNA and DNA, as well as ATP, NADH, FAD, and coenzyme A.

In the nonoxidative phase, the pathway catalyzes the interconversion of three-, four-, five-, six-, and seven-carbon sugars in a series of nonoxidative reactions that can result in the synthesis of five-carbon sugars for nucleotide biosynthesis or the conversion of excess five-carbon sugars into intermediates of the glycolytic pathway. All these reactions take place in the cytosol. These interconversions rely on the same reactions that lead to the regeneration of ribulose 1,5-bisphosphate in the Calvin cycle.

The oxidative phase of the pentose phosphate pathway starts with the dehydrogenation of glucose 6-phosphate at carbon 1, a reaction catalyzed by glucose 6-phosphate dehydrogenase (Figure 20.20). This enzyme is highly specific for NADP⁺; the K_M for NAD⁺ is about a thousand times as great as that for NADP⁺. The product is 6-phosphoglucono-δ-lactone, which is an intramolecular ester between the C-1 carboxyl group and the C-5 hydroxyl group. The next step is the hydrolysis of 6-phosphoglucono-δ-lactone by a specific lactonase to give 6-phosphogluconate. This six-carbon sugar is then oxidatively decarboxylated by 6-phosphogluconate dehydrogenase to yield ribulose 5-phosphate. NADP⁺ is again the electron acceptor. The final step in the synthesis of ribose 5-phosphate is the isomerization of ribulose 5-phosphate by phosphopentose isomerase (see Figure 20.11)

The preceding reactions yield two molecules of NADPH and one molecule of ribose 5-phosphate for each molecule of glucose 6-phosphate oxidized. However, many cells need NADPH for reductive biosyntheses much more than they need ribose 5-phosphate for incorporation into nucleotides and nucleic acids. In these cases, ribose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate by transketolase and transaldolase. These enzymes create a reversible link between the pentose phosphate pathway and glycolysis by catalyzing these three successive reactions.

The net result of these reactions is the formation of two hexoses and one triose from three pentoses:

The first of the three reactions linking the pentose phosphate pathway and glycolysis is the formation of glyceraldehyde 3-phosphate and sedohep-tulose 7-phosphate from two pentoses.

The donor of the two-carbon unit in this reaction is xylulose 5-phosphate, an epimer of ribulose 5-phosphate. A ketose is a substrate of transketolase only if its hydroxyl group at C-3 has the configuration of xylulose rather than ribulose. Ribulose 5-phosphate is converted into the appropriate epimer for the transketolase reaction by phosphopentose epimerase (see Figure 20.11) in the reverse reaction of that which occurs in the Calvin cycle.

Glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate generated by the transketolase then react to form fructose 6-phosphate and erythrose 4-phosphate.

This synthesis of a four-carbon sugar and a six-carbon sugar is catalyzed by transaldolase.

In the third reaction, transketolase catalyzes the synthesis of fructose 6-phosphate and glyceraldehyde 3-phosphate from erythrose 4-phosphate and xylulose 5-phosphate.

The sum of these reactions is

Xylulose 5-phosphate can be formed from ribose 5-phosphate by the sequential action of phosphopentose isomerase and phosphopentose epimerase, and so the net reaction starting from ribose 5-phosphate is

Thus, excess ribose 5-phosphate formed by the pentose phosphate pathway can be completely converted into glycolytic intermediates. Moreover, any ribose ingested in the diet can be processed into glycolytic intermediates by this pathway. It is evident that the carbon skeletons of sugars can be extensively rearranged to meet physiologic needs (Table 20.3).