Differences in the allosteric properties of pure low and high phosphate forms of phosphofructokinase from rat liver (original) (raw)

The effect of natural and synthetic D-fructose 2,6-bis- phosphate on the kinetic properties of liver and muscle phosphofructokinases. J Biol Chem 256: 8394-8499

Journal of Biological Chemistry

The effect of natural "activation factor" and synthetic fructose-2,6-Pz on the allosteric kinetic properties of liver and muscle phosphofructokinases was investigated. Both synthetic and natural fructose-2,6-Pz show identical effects on the allosteric kinetic properties of both enzymes. Auctose-2,6-Pz counteracts inhibition by ATP and citrate and decreases the K,,, for fructose-6-P. This fructose ester also acts synergistically with AMP in releasing ATP inhibition. The K,,, values of liver and muscle phosphofructokinase for fructose-2,6-Pz in the presence of 1.26 IMI ATP are 12 milliunits/ml (or 24 l ũ r ) and 5 milliunits/ml (or 10 m), respectively. At near physiological concentrations of ATP (3 1 1 1 ) and fructose-6-P (0.2 m), however, the K,,, values for fructose-2,6-Pz are increased to 12 PM and 0.8 p t for liver and muscle enzymes, respectively. Thus, fructose-2,6-Pz is the most potent activator of the enzyme compared to other known activators such as fructose-1,6-Pz. The rates of the reaction catalyzed by the enzymes under the above conditions are nonlinear: the rates decelerate in the absence or in the presence of lower concentrations of fructose-2,6-Pz, but the rates become linear in the presence of higher concentrations of fructose-2,6-Pz. Fructose-2,6-Pz also protects phosphofructokinase against inactivation by heat. Fructose-2,6-Pz, therefore, may be the most important allosteric effector in regulation of phosphofructokinase in liver as well as in other tissues.

The effect of natural and synthetic d-fructose 2,6-bisphosphate on the regulatory kinetic properties on liver and muscle phosphofructokinases

The effect of natural "activation factor" and synthetic fructose-2,6-Pz on the allosteric kinetic properties of liver and muscle phosphofructokinases was investigated. Both synthetic and natural fructose-2,6-Pz show identical effects on the allosteric kinetic properties of both enzymes. Auctose-2,6-Pz counteracts inhibition by ATP and citrate and decreases the K,,, for fructose-6-P. This fructose ester also acts synergistically with AMP in releasing ATP inhibition. The K,,, values of liver and muscle phosphofructokinase for fructose-2,6-Pz in the presence of 1.26 IMI ATP are 12 milliunits/ml (or 24 l ũ r ) and 5 milliunits/ml (or 10 m), respectively. At near physiological concentrations of ATP (3 1 1 1 ) and fructose-6-P (0.2 m), however, the K,,, values for fructose-2,6-Pz are increased to 12 PM and 0.8 p t for liver and muscle enzymes, respectively. Thus, fructose-2,6-Pz is the most potent activator of the enzyme compared to other known activators such as fructose-1,6-Pz. The rates of the reaction catalyzed by the enzymes under the above conditions are nonlinear: the rates decelerate in the absence or in the presence of lower concentrations of fructose-2,6-Pz, but the rates become linear in the presence of higher concentrations of fructose-2,6-Pz. Fructose-2,6-Pz also protects phosphofructokinase against inactivation by heat. Fructose-2,6-Pz, therefore, may be the most important allosteric effector in regulation of phosphofructokinase in liver as well as in other tissues.

Chicken liver phosphofructokinase. III. Kinetics and allosteric properties

Journal of Biological Chemistry

Some kinetic and allosteric properties of crystalline chicken liver phosphofructokinase were investigated. Lineweaver-Burk plots with fructose 6.phosphate and ATP as substrates yield a series of apparently parallel lines. The liver enzyme also catalyzes the phosphorylation of fructose-l-P, and the double reciprocal plot with fructose-l-P as the substrate yields intersecting lines. Phosphorylation of both fructose-6-P and fructose-l-P are lost at 4" at equal rate. Of the many sugar phosphates examined, only glucose-6-P, 6-P.

An activation factor of liver phosphofructokinase

Proceedings of the National Academy of Sciences, 1980

Pure phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) from liver is strongly inhibited by ATP, whereas crude phosphofructokinase is only slightly inhibited by ATP. A factor that is removed from the enzyme during purification and can prevent the inhibition of phosphofructokinase by ATP has been isolated. The factor can be resolved into three components that differ in molecular weights, as shown by gel filtration on Sephadex G-25. These factors overcome the ATP inhibition but have no effect on the catalytic activity under the optimum assay conditions. Furthermore, AMP acts syngeristically with the activation factor in reversing ATP inhibition. It is proposed that the activation of phosphofructokinase by the activation factor and AMP is sufficient to account for the glycolytic flux in the liver.

Kinetic characterization of phosphofructokinase isolated from rat kidney cortex

Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1991

Phosphofructokinase from rat kidney cortex has been purified by affinity chromatography to a final specific activity of 15 units per mg of protein, measured at 25°C and pH 8. 2. This lower spec. act., compared with that of the enzyme from other sources, shows the enzyme in proximal tubules to be less active, which would account for the main gluconeogenic role of these nephron sections. 3. The binding of fructose-6-phosphate to the enzyme is cooperative. ATP increases the Hill coefficient and produces a marked allosteric inhibition on the activity. 4. Fructose-2,6-b/s-phosphate is a potent activator of the enzyme from this source. It reduces the Hill coefficient of the enzyme and the inhibition constant of ATP. A marked difference between this and the liver enzyme is that the activation is not cooperative .

Significance of phosphorylation of phosphofructokinase

Journal of Biological Chemistry

In order to understand the effect of phosphorylation on phosphofructokinase, the allosteric kinetic behavior, ligand binding at various pHs, and pH-dependent cold inactivation of phosphofructokinase phosphorylated to different extents were studied.

Activation of muscle phosphofructokinase by α-glucose 1,6-bisphosphate and fructose 2,6-bisphosphate is differently affected by other allosteric effectors and by pH

Biochemical and Biophysical Research Communications, 1988

Citrate, ATP and AMP affect similarly the activation of muscle phosphofructokinase by a-glucose 1,6-bisphosphate and fructose 1,6bisphosphate, but they affect differently its activation by fructose 2,6-bisphosphate. Activation by a-glucose 1,6-bisphosphate and fructose 2,6-bisphosphate is also differently affected by pH. This suggest that beth u-glucose 1,6-bisphosphate and fructose 1,6-bisphosphate induce thesame conformational change on muscle phosphofructokinase, distinct fromthat produced by fructose 2,6-bisphosphate.

Control of the fructose-6-phosphate/fructose 1,6-bisphosphate cycle in isolated hepatocytes by glucose and glucagon. Role of a low-molecular-weight stimulator of phosphofructokinase

The Biochemical journal, 1980

1. Recycling of metabolites between fructose 6-phosphate and triose phosphates has been investigated in isolated hepatocytes by the randomization of carbon between C((1)) and C((6)) of glucose formed from [1-(14)C]galactose. 2. Randomization of carbon atoms was regularly observed with hepatocytes isolated from fed rats and was then little influenced by the concentration of glucose in the incubation medium. It was decreased by about 50% in the presence of glucagon. 3. Randomization of carbon atoms by hepatocytes isolated from starved rats was barely detectable at physiological concentrations of glucose in the incubation medium, but was greatly increased with increasing glucose concentrations. It was nearly completely suppressed by glucagon. These large changes can be attributed to parallel variations in the activity of phosphofructokinase. 4. The main factors that appear to control the activity of phosphofructokinase under these experimental conditions are the concentration of fructo...