(2) 3-Phosphoglycerate

(2) 2-Phosphoglycerate

pyruvate kinase

(2) Pyruvate

(2) Phosphoenolpyruvate

(2) Pyruvate f

^^ PEP carboxykinase

(2) Oxaloacetate (2) ADP

pyruvate carboxylase

Gluconeogenesis and glycolysis are not identical pathways running in opposite directions, although they do share several steps (Fig. 14-16); seven of the ten enzymatic reactions of gluconeogenesis are the reverse of glycolytic reactions. However, three reactions of glycol-ysis are essentially irreversible in vivo and cannot be used in gluconeogenesis: the conversion of glucose to glucose 6-phosphate by hexokinase, the phosphoryla-tion of fructose 6-phosphate to fructose 1,6-bisphos-phate by phosphofructokinase-1, and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase (Fig. 14-16). In cells, these three reactions are charac

FIGURE 14-16 Opposing pathways of glycolysis and gluconeogenesis in rat liver. The reactions of glycolysis are shown on the left side in blue; the opposing pathway of gluconeogenesis is shown on the right in red. The major sites of regulation of gluconeogenesis shown here are discussed later in this chapter, and in detail in Chapter 15. Figure 14-19 illustrates an alternative route for oxaloacetate produced in mitochondria.

terized by a large negative free-energy change, AG, whereas other glycolytic reactions have a AG near 0 (Table 14-2). In gluconeogenesis, the three irreversible steps are bypassed by a separate set of enzymes, catalyzing reactions that are sufficiently exergonic to be effectively irreversible in the direction of glucose synthesis. Thus, both glycolysis and gluconeogenesis are irreversible processes in cells. In animals, both pathways occur largely in the cytosol, necessitating their reciprocal and coordinated regulation. Separate regulation of the two pathways is brought about through controls exerted on the enzymatic steps unique to each.

We begin by considering the three bypass reactions of gluconeogenesis. (Keep in mind that "bypass" refers throughout to the bypass of irreversible glycolytic reactions.)

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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