7.7 Additional roles of gluconeogenetic enzymes

Two enzymes that occur in gluconeogenesis have important roles in other metabolic pathways. One of them is glucose-6-phosphatase. Glucose-6-phosphate can be generated not only by gluconeogenesis but also during degradation of glycogen, the polymeric storage form of glucose (see subsequent chapter). It likewise must undergo dephosphorylation to glucose by glucose-6-phosphatase before release into the bloodstream.

The other enzyme that deserves mention is pyruvate carboxylase. If you look at Figure 1.3-1, you will see that pyruvate can enter the TCA via two routes: As a substrate (after conversion to acetyl-CoA) and as an intermediate (as oxaloacetate). If a shortage of TCA intermediates occurs, acetyl-CoA will back up. Acetyl-CoA will allosterically activate of pyruvate carboxylase, which will help to restore the level of TCA intermediates back to normal.

Pyruvate carboxylase can also help to provide NADPH, which otherwise is provided prominently by the hexose monophosphate shunt. Oxaloacetate is reduced to malate by malate dehydrogenase (which reaction is part of the TCA but also occurs in the cytosol), and malate is cleaved by malic enzyme, which yields pyruvate and NADPH. This reaction is discussed in more detail in section 12.1.