Regulation of Glycolysis and Gluconeogenesis

When focusing on the energetics of these pathways, it is appropriate to consider the pathway as a whole. But when considering problems of regulation, it is more useful to look at the small pseudocycles where the regulatory enzymes are 

We will focus our discussion on the well-understood regulatory enzymes that modulate the flux between glycogen and the hexose monophosphate pool (pseudocycle la), and between fructose-6-phosphate and fructose-1,6-bisphosphate (pseudocycle II). Some aspects of the regulation between the 3-carbon pool and pyruvate (pseudocycle III) are discussed in the next chapter. 

As an analogy, consider a river with a dam somewhere between its source and its terminus. If the flood gates of the dam are opened, the flow of water transiently increases everywhere in the river. At sites near the end of the river, the increase in the flow can be explained simply by the increased pressure of water coming from upstream at sites near the source, it can be attributed to a reduced pressure downstream. Only at the site of the dam is the situation reversed the flow of water increases here in spite of the fact that the pressure downstream has risen and the pressure upstream has fallen. 

Phosphofructokinase and the other enzymes that regulate pseudocycles I, IL and III of glycolysis are influenced by both intracellular and extracellular signals. We consider some of the intracellular signals first. 

The paired enzymes that regulate flux at pseudocycle I (la) are affected in a parallel way by the same small-molecule allosteric effectors. A summary of the results for the four regulatory enzymes associated with pseudocycles la and II is presented in table 12.2. 

---

Regulation of glycolysis and gluconeogenesis by ATP/ADP concentration ratio in the liver... 

We begin our examination of the coordinated regulation of glycolysis and gluconeogenesis by considering the regulatory patterns seen at the three main control... 

Fructose 2,6-Bisphosphate Is a Potent Regulator of Glycolysis and Gluconeogenesis... 

The hormonal regulation of glycolysis and gluconeogenesis is mediated by fructose 2,6-bisphosphate, an allosteric effector for the enzymes PFK-1 and FBPase-1 (Fig. 15-22) ... 

Summary of the Regulation of Glycolysis and Gluconeogenesis The Pentose Phosphate Pathway... 

F2,6BP is one of the most important compounds involved in allosteric regulation of glycolysis and gluconeogenesis. 

PFK2 catalyzes formation of the compound fimctose-2,6-bisphosphate (F2,6BP) by transferring a phosphate from ATP onto position 2 of fructose-6-phosphate (F6P) (Figure 16.7). F2,6BP is the most important allosteric regulator of glycolysis and gluconeogenesis and is formed as follows ... 

Allosteric activators of PFK include AMP and fructose-2,6-bisphosphate (F2,6BP). Inhibitors include ATP and citrate. The most potent of the allosteric regulator of glycolysis and gluconeogenesis is F2,6BP due to its ability to turn on PFK and turn off the corresponding gluconeogenesis enzyme, fructose-1,6-bisphosphatase, in very low concentrations. 

Other reciprocal regulators of glycolysis and gluconeogenesis are fructose-2,6-bisphosphate and acetyl-CoA. See Figure 16.7 for additional details about the reciprocal regulatory mechanisms of action of fructose-2,6-bisphophate. 

---