SUMMARY

• 26.1 The Pentose Phosphate Pathway Yields NADPH and Five-Carbon Sugars

  The pentose phosphate pathway, present in all organisms, generates NADPH and ribose 5-phosphate in the cytoplasm. NADPH is used in reductive biosyntheses, whereas ribose 5-phosphate is used in the synthesis of RNA, DNA, and nucleotide coenzymes. The pentose phosphate pathway starts with the dehydrogenation of glucose 6-phosphate to form a lactone, which is hydrolyzed to give 6-phosphogluconate and then oxidatively decarboxylated to yield ribulose 5-phosphate. NADP⁺ is the electron acceptor in both of these oxidations. Ribulose 5-phosphate (a ketose) is subsequently isomerized to ribose 5-phosphate (an aldose). A different mode of the pathway is active when cells need much more NADPH than ribose 5-phosphate. Under these conditions, ribose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate by transketolase and transaldolase. These two enzymes create a reversible link between the pentose phosphate pathway and gluconeogenesis. Xylulose 5-phosphate, sedoheptulose 7-phosphate, and erythrose 4-phosphate are intermediates in these interconversions. In this way, 12 molecules of NADPH can be generated for each molecule of glucose 6-phosphate that is completely oxidized to CO₂.

• 26.2 Metabolism in Context: Glycolysis and the Pentose Phosphate Pathway Are Coordinately Controlled

  Only the nonoxidative branch of the pathway is significantly active when much more ribose 5-phosphate than NADPH needs to be synthesized. Under these conditions, fructose 6-phosphate and glyceraldehyde 3-phosphate (formed by the glycolytic pathway) are converted into ribose 5-phosphate without the formation of NADPH. Alternatively, ribose 5-phosphate formed by the oxidative branch can be converted into pyruvate through fructose 6-phosphate and glyceraldehyde 3-phosphate. In this mode, ATP and NADPH are generated, and five of the six carbon atoms of glucose 6-phosphate emerge in pyruvate. The interplay of the glycolytic and pentose phosphate pathways enables the concentrations of NADPH, ATP, and building blocks such as ribose 5-phosphate and pyruvate to be continually adjusted to meet cellular needs.

  484

• 26.3 Glucose 6-phosphate Dehydrogenase Lessens Oxidative Stress

  NADPH generated by glucose 6-phosphate dehydrogenase maintains the appropriate concentration of reduced glutathione required to combat oxidative stress and maintain the proper reducing environment in the cell. Cells with diminished glucose 6-phosphate dehydrogenase activity are especially sensitive to oxidative stress.