Fructose 1,6-bisphosphatase , inhibition

Fructose 1,6-bisphosphatase Inhibited by F-2,6-P, AMP Induced during fasting... 

Because the enzyme extracts were made from acetone-dried powders, they were free of all nucleotides (40, 42). This strategy confined the dissimilation of labeled Rib 5-P to a hexose 6-P end point. Glc 6-P could not recycle, and the labeled prediction pattern was not scrambled. Mg + was also omitted from the reaction mixture to inhibit the activity of Fructose bisphosphatase (EC 3.1.3.11) and production of a contaminating Fru 6-P from Fru 1,6-P2 formed by aldolase and the triose-P products of the TK reactions. It is curious that Fru 1,6-P2, which is an Aid product, was formed (Fig. 3) by the hver and pea tissue reaction mixtures but was omitted from the final construction of the scheme for Fig. 2. 

The hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate (Eigure 23.7), like all phosphate ester hydrolyses, is a thermodynamically favorable (exergonic) reaction under standard-state conditions (AG° = —16.7 kj/mol). Under physiological conditions in the liver, the reaction is also exergonic (AG = —8.6 kJ/mol). Fructose-1,6-bisphosphatase is an allosterically regulated enzyme. Citrate stimulates bisphosphatase activity, hut fructose-2,6-bisphosphate is a potent allosteric inhibitor. / MP also inhibits the bisphosphatase the inhibition by / MP is enhanced by fructose-2,6-bisphosphate. 

FIGURE 23.12 Inhibition of fructose-1,6-bisphosphatase by fructose-2,6-bisphosphate in the (a) absence and (b) presence of 25 /xM AMP. In (a) and (b), enzyme activity is plotted against substrate (fructose-1,6-bisphosphate) concentration. Concentrations of fructose-2,6-bisphosphate (in fiM) are indicated above each curve, (c) The effect of AMP (0, 10, and 25 fiM) on the inhibition of fructose-1,6-bisphosphatase by fructose-2,6-bisphos-phate. Activity was measured in the presence of 10 /xM fructose-1,6-bisphosphate. 

The most potent positive allosteric effector of phospho-ffuctokinase-1 and inhibitor of fructose-1,6-bisphos-phatase in liver is fructose 2,6-bisphosphate. It relieves inhibition of phosphofructokinase-1 by ATP and increases affinity for fructose 6-phosphate. It inhibits fructose-1,6-bisphosphatase by increasing the for fructose 1,6-bisphosphate. Its concentration is under both substrate (allosteric) and hormonal control (covalent modification) (Figure 19-3). 

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. 

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,... 

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.]... 

Fructose 1,6-bisphosphate is converted to fructose 1-phosphate by fructose 1,6-bisphosphatase. This enzyme is inhibited by elevated levels of AMP and activated by elevated levels of ATP. The enzyme is also inhibited by fructose 2,6-bisphosphate, the... 

Answer Ribulose 5-phosphate kinase, fructose 1,6-bisphosphatase, sedoheptulose 1,7-bisphosphatase, and glyceraldehyde 3-phosphate dehydrogenase would be inhibited. All have mechanisms requiring activation by reduction of a critical disulfide bond to a pair of —SH groups. Iodoacetate reacts irreversibly with free —SH groups. 

Fructose 1,6-bisphosphatase is inhibited by AMP but activated by citrate and 3-phosphoglycerate. Thus, in a high-bond-energy state, an increase of citrate and a decrease of AMP combine to activate fructose-1,6-bisphosphatase and to inhibit phosphofructokinase (Fig. 11-10). This promotes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate. 

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