A model for glycolytic oscillations based on skeletal muscle phosphofructokinase kinetics.
Existing models for glycolytic oscillations are not based on detailed experimental kinetics of the glycolytic enzymes. Here, a model is constructed to fit the kinetics of skeletal muscle phosphofructokinase with respect to variations in AMP, ATP, fructose-6-P, and fructose 1,6-P2 levels. A Monod-Wyman-Changeux model for a tetrameric enzyme is considered. However, it is found that the kinetic data fit considerably better with an assumption of identical, independent subunits. With parameters that fit these data and with a previous model for the rest of glycolysis, product activation of phosphofructokinase leads to oscillations of glycolytic intermediates and [ATP] resembling those observed experimentally in muscle extracts. The period is several minutes. The model can also produce oscillations at neutral pH and with [ATP] representative of an intact cell. Under both conditions the mean concentrations and oscillations vary with the rate of glucose phosphorylation in a plausible manner only if some amount of glucose-6-phosphatase or glucose-6-P dehydrogenase activity is assumed or if hexokinase is inhibited by glucose-6-P. Also, the model can be reduced to two variables for ease of analysis and the oscillation mechanism thereby illustrated.
Smolen
P
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Mathematical Research Branch, NIDDK, NIH, Bethesda, MD 20892, USA.
D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D006019:Glycolysis; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000378:metabolism*
D005636:Fructosephosphates; D000249:Adenosine Monophosphate; C027618:fructose-6-phosphate; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D006597:Fructose-Bisphosphatase