The Pentose Phosphate Pathway
The pentose phosphate pathway (PPP) generates NADPH for use in reductive biosynthesis. NADPH is used in the synthesis of fatty acids, cholesterol, neurotransmitters, and nucleotides. In the oxidative phase of the PPP, which will be the only phase looked at on this site, NADPH is generated when glucose-6-phosphate is oxidized to ribose-5-phosphate.
The oxidative phase of the PPP begins with the dehydrogenation of glucose-6-phosphate, catalyzed by glucose-6-phosphate dehydrogenase, which is specific for NADP+. This step is followed by hydrolysis by lactonase, giving 6-phosphogluconate. 6-phosphogluconate is then oxidatively decarboxylated by 6-phosphogluconate dehydrogenase to yield ribulose-5-phosphate, NADP+ again is the electron acceptor. Finally, isomerization to ribose-5-phosphate.
Ribose-5-phosphate can be converted to glyceraldehyde-3-phosphate and fructose-6-phosphate by transketolase and transaldolase, forming a reversible link between the PPP and glycolysis. Essentially, two hexoses and one triose are formed.
Glucose-6-Phosphate Dehydrogenase
Reactive oxygen species generated in oxidative metabolism inflict damage on all classes of molecules. Reduced glutathione combats oxidative stress by reducing ROS to a harmless form. Now that glutathione is in its oxidated form, it must be reduced itself. This is done by the NADPH generated by glucose-6-phosphate dehydrogenase in the PPP.
Cells with reduced glucose-6-phosphate dehydrogenase levels are at increased sensitivity to oxidative stress because they produce less NADPH needed to restore the antioxidant glutathione to its reduced form. The reduction of oxidized glutathione is catalyzed by glutathione reductase. Electrons from NADPH are transferred from NADPH to a bound FAD on the reductase, and then to a disulfide bridge in the enzyme subunits, and finally to glutatione.
Berg, J., Tymoczko, J., Stryer, L. Biochemistry 6E. ©2007 W.H. Freeman and Company
