Fructose 1,6-bisphosphatase gluconeogenesis

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

Aldolase and Fructose Bisphosphatase Key Enzymes in the Control of Gluconeogenesis and Glycolysis B. L. Horecker, John S. MacGregor,... 

For all of these reactions, the equilibrium is in the direction of glycolysis, because of the utilization of ATP in the reaction and the high ratio of ATP to ADP in the cell. The reactions of phosphofructokinase and hexokinase are reversed in gluconeogenesis by simple hydrolysis of fructose bisphosphate to fructose 6-phosphate plus phosphate (catalysed by fructose bisphosphatase) and of glucose 6-phosphate to glucose plus phosphate (catalysed by glucose 6-phosphatase). 

The other reactions of glycolysis are readily reversible, and the overall direction of metabolism, either glycolysis or gluconeogenesis, depends mainly on the relative activities of phosphofructokinase and fructose bisphosphatase, as discussed in section 10.2.2. 

Fructose-2,6-bisphosphatase, a regulatory enzyme of gluconeogenesis (Chapter 19), catalyzes the hydrolytic release of the phosphate on carbon 2 of fructose 2,6-bisphosphate. Figure 7-8 illustrates the roles of seven active site residues. Catalysis involves a catalytic triad of one Glu and two His residues and a covalent phos-phohistidyl intermediate. 

Fructose-1,6-bisphosphatase is an important rate-limiting step in gluconeogenesis. This gluconeogenic step antagonizes the opposite reaction that forms fructose-1, 6-bisphosphate from fmctose-6-phosphate and ATP... 

Fructose 2,6-bisphosphate is not a metabolic intermediate but an allosteric regulator. It has two important roles it increases the activity of PFK-1 but decreases the activity of fructose 1,6-bisphosphatase (FBPase). Consequently an increase in the concentration of fructose 2,6-bisphosphate favours glycolysis but restricts gluconeogenesis. 

The reaction catalyzed by fructose 1,6-bisphosphatase is an important regulation point in gluconeogenesis (see p. 158). 

Fructose 2,6-bisphosphate (Fru-2,6-bP) plays an important part in carbohydrate metabolism. This metabolite is formed in small quantities from fructose 6-phosphate and has purely regulatory functions. It stimulates glycolysis by allosteric activation of phosphofructokinase and inhibits gluconeogenesis by inhibition of fructose 1,6-bisphosphatase. 

Phosphofructokinase-2/fructose 2,6-bisphosphatase LQRRRGSSIPQ Glycolysis/gluconeogenesis... 

The second glycolytic reaction that cannot participate in gluconeogenesis is the phosphorylation of fructose 6-phosphateby PFK-1 (Table 14-2, step ). Because this reaction is highly exergonic and therefore irreversible in intact cells, the generation of fructose 6-phosphate from fructose 1,6-bisphosphate (Fig. 14-16) is catalyzed by a different enzyme, Mg2+-dependent fructose 1,6-bisphosphatase (FBPase-1), which promotes the essentially irreversible hydrolysis of the C-l phosphate (not phosphoiyl group transfer to ADP) ... 

Fructose 1,6-bisphosphatase is inhibited by AMP—a compound that activates phosphofructokinase Elevated AMP thus stimulates path ways that oxidize nutrients to provide energy for the cell. [Note ATP and NADH, produced in large quantities during fasts by catalytic path ways, such as fatty acid oxidation, are required for gluconeogenesis.]... 

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