6-phosphofructokinase-1 PFK

C. The key regulatory enzyme phosphofructokinase-1 (PFK-1) catalyzes the synthesis of fructose 1,6-hisphosphate. 

Phosphorylation of Fructose 6-Phosphate to Fructose 1,6-Bisphosphate In the second of the two priming reactions of glycolysis, phosphofructokinase-1 (PFK-1) catalyzes the transfer of a phosphoryl group from ATP to fructose 6-phosphate to yield fructose 1,6-bisphos-phate ... 

Other reactions are far from equilibrium in the cell. For example, for the phosphofructokinase-1 (PFK-1) reaction in glycolysis is about 1,000, but Q ([fructose 1,6-bisphosphate] [ADP] / [fructose 6-phosphate] [ATP]) in a typical cell in the steady state is about 0.1 (Table 15-2). It is because the reaction is so far from equilibrium that the process is exergonic under cellular con-... 

FIGURE 15-21 Regulation of fructose 1,6-bisphosphatase-1 (FBPase-1) and phosphofructokinase-1 (PFK-1). The important role of fructose 2,6-bisphosphate in the regulation of this substrate cycle is detailed in subsequent figures. 

Three glycolytic enzymes are subject to allosteric regulation hexoldnase IV, phosphofructokinase-1 (PFK-1), and pyruvate kinase. 

The phosphorylation of fructose-6-phosphate. Phosphofructokinase-1 (PFK-1) irreversibly catalyzes the phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate ... 

For lipogenesis, glucose 6-phosphate is converted through glycolysis to pyruvate. Key enzymes that regulate this pathway in the liver are phosphofructokinase-1 (PFK-1) and pyruvate kinase. PFK-1 is aliosterically activated in the fed state by fructose 2,6-bisphosphate and adenosine monophosphate (AMP) (see Fig. 36.1). Phosphofructokinase-2, the enzyme that produces the activator fructose 2,6-bisphosphate, is dephosphorylated and active after a meal (see Chapter 22). Pyruvate kinase is also activated by dephosphorylation, which is stimulated by the increase of the insulin/glucagon ratio in the fed state (see Fig. 36.1). 

Figure 19-3. Control of glycolysis and gluconeoge-nesis in the liver by fructose 2,6-bisphosphate and the bifunctional enzyme PFK-2/F-2,6-Pase (6-phospho-fructo-2-kinase/fructose-2,6-bisphosphatase). (PFK-1, phosphofructokinase-1 [6-phosphofructo-1 -kinase] ...

Phosphofructokinase-1 is a regulatory enzyme (Chapter 6), one of the most complex known. It is the major point of regulation in glycolysis. The activity of PFK-1 is increased whenever the cell s ATP supply is depleted or when the ATP breakdown products, ADP and AMP (particularly the latter), are in excess. The enzyme is inhibited whenever the cell has ample ATP and is well supplied by other fuels such as fatty acids. In some organisms, fructose 2,6-bisphosphate (not to be confused with the PFK-1 reaction product, fructose 1,6-bisphosphate) is a potent allosteric activator of PFK-1. The regulation of this step in glycolysis is discussed in greater detail in Chapter 15. 

The flow of triose phosphates into sucrose is regulated by the activity of fructose 1,6-bisphosphatase (FBPase-1) and the enzyme that effectively reverses its action, PPrdependent phosphofructokinase (PP-PFK-1 p. 527). These enzymes are therefore critical points for determining the fate of triose phosphates produced by photosynthesis. Both enzymes are regulated by fructose 2,6-bisphosphate (F2,6BP), which inhibits FBPase-1 and stimulates PP-PFK-1. In vascular plants, the concentration of F2,6BP varies inversely with the rate of photosynthesis (Fig. 20-26). Phosphofructokinase-2,... 

Fig. 31.17. Regulation of gluconeogenesis in the liver. GK = glucokinase G-6-Pase = glucose 6-phosphatase PK = pyruvate kinase OAA = oxaloacetate PEPCK = phosphoenolpyruvate carboxykinase F-1,6-Pase = fructose 1,6-bisphosphatase F-2,6-P = fructose 2,6-bisphosphate PFK-1 = phosphofructokinase-1.

In addition to stimulating the synthesis and release of LPL, insulin stimulates glucose metabolism in adipose cells. Insulin leads to the activation of the glycolytic enzyme phosphofructokinase-1 by an activation of PFK-2, which increases fructose 2,6-bisphosphate levels. Insulin also stimulates the dephosphorylation of pyruvate dehydrogenase, so that the pyruvate produced by glycolysis can be oxidized in the TCA cycle. Furthermore, insulin stimulates the conversion of glucose to fatty acids in adipose cells, although the liver is the major site of fatty acid synthesis in humans. 

PPi-PFK <1, 30, 35, 37-39, 41, 44> [31-33, 35, 36, 38-40, 44, 47] PPi-dependent phosphofructokinase <1, 35, 37, 39, 40> [33, 35, 39-41] diphosphate-D-fructose-6-phosphate 1 -phosphotransferase fructose 1,6-bisphosphatase <42> [45] inorganic pyrophosphate-dependent phosphofructokinase inorganic pyrophosphate-phosphofructokinase phosphotransferase, pyrophosphate-D-fructose 6-phosphate 1-pyrophosphate D-fructose-6-phosphate 1-phosphotransferase pyrophosphate-D-fructose 6-phosphate 1-phosphotransferase pyrophosphate-D-fructose 6-phosphate 1-phosphotransferase pyrophosphate-D-fructose 6-phosphate phosphotransferase pyrophosphate-dependent phosphofructo-1 -kinase pyrophosphate-dependent phosphofructokinase... 

Ate, adenylate energy charge CF, chloroplast coupling factor 1 PFK, phosphofructokinase PK, pyruvate kinase GK, glycerokinase PMS, phenazi nemethosulfate. 

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