A kinetic model of phosphofructokinase from Plasmodium berghei. Influence of ATP and fructose-6-phosphate.
Phosphofructokinase (PFK) from the malarial parasite Plasmodium berghei shows the following kinetic features: the more the pH is decreased, the more the enzyme is inhibited by ATP; in contrast to PFK from erythrocytes, this inhibition is less potent by two orders of magnitude; as in the red cell, fructose-6-phosphate (F6P) is a positive effector. Kinetic modelling of PFK from P. berghei has been performed by taking the pH-dependence of activity into regard, implicitly by the estimation of pH-dependent kinetic parameters for the inhibition by ATP and the activation by F6P and explicitly by the assumption of protonation-steps involved in allosteric regulation. By means of a novel procedure of model discrimination [D. Buckwitz and H.-G. Holzhütter: A new method to discriminate between enzyme-kinetic models. In: Application of Computational Methods in Medicine (Györi, I., ed.), Akademai, Budapest, in press] we have selected among several kinetic models the best rate equation which provides an adequate quantitative description of the kinetic behaviour of the enzyme in the relevant ranges of substrate concentrations and pH (5.8-7.6). It thus becomes clear how the highly increased glycolytic flux in malaria-infected cells could be affected through PFK.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005636:Fructosephosphates / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010962:Plasmodium berghei / Q000201:enzymology*
D005636:Fructosephosphates; C027618:fructose-6-phosphate; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1