9 The hexose monophosphate shunt
9.1 Reactions in the hexose monophosphate shunt
9.2 Why do we need both NADH and NADPH?
9.3 Alternative sources of NADPH
9.4 Uses of NADPH
9.5 Glucose-6-phosphate dehydrogenase deficiency
We are (finally) nearly done with glucose-6-phosphate. Figure 9-1 summarizes the various pathways that it is part of, and I hope that by now you recognize most of them. The final one of these pathways to be covered in this class is the hexose monophosphate shunt. Since both pentoses and hexoses (as well as trioses, tetraoses, and heptoses) occur in it, this pathway is sometimes also referred to as the 'pentose phosphate pathway'.
A single passage of glucose-6-phosphate through the hexose monophosphate shunt oxidizes it to the C5-sugar ribulose-5-phosphate, releasing one molecule of CO2. In the process, two molecules of hydrogen are transferred to NADP+, yielding NADPH.
The ribulose-5-phosphate can be turned into ribose-5-phosphate and then used for the biosynthesis of nucleotides. Alternatively, it can be fully oxidized to yield more CO2 and NADPH (Figure 9-2). The hexose monophosphate shunt therefore provides a second means for complete degradation of glucose to CO2, apart from the the glycolysis / TCA pathway we have seen before. The purpose of this second oxidative pathway consists not in the regeneration of ATP but in the formation of NADPH. This coenzyme is required in many biosynthetic reactions, some of which we will consider below. Glycolysis and TCA don't fill this need, because all hydrogen they abstract accumulates as NADH or FADH2.
Dehydrogenation of pyruvate and the TCA occur in the mitochondria, which is useful because the NADH generated is then fed into the respiratory chain. In contrast, the hexose monophosphate shunt occurs entirely in the cytoplasm. This is in keeping with the fact that most of the biosynthetic reactions involving NADPH also occur in the cytoplasm (or in the ER, which is still outside the mitochondrion).