The Hexose MonoPhosphate Shunt is also known as “Pentose phosphate Pathway” (PPP). This is alternative Glucose oxidation pathway. The hexose monophosphate pathway is used for production of NADPH from NADP. The NADPH is required for biosynthetic reactions such as fatty acid synthesis, cholesterol synthesis, drug reduction, and as a cofactor for some non-synthetic enzymatic reactions. In addition, it is used for the production of ribose for nucleotide and nucleic acid synthesis. The hexose monophosphate pathway also allows the entry of some carbohydrates into the glycolytic pathway (especially ribose, but also some others), and therefore acts as a connection route between different pathways. Steroidogenic tissues, red blood cells, and the liver are the major sites of hexose monophosphate pathway. Muscle has small amounts of some of the hexose monophosphate pathway enzymes, because it has little need for synthetic reactions, and therefore, little need for NADPH. The muscle, however, like all tissues, needs to be able to synthesize ribose in order to make nucleotides and nucleic acids.
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. 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).