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A Simulation Study of Mammalian Phosphofructokinase

From the ¹ From the Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania 19104

A computer model of the mammalian muscle phosphofructokinase system (with associated chemical reactions) has been constructed in which 22 differential equations represent 22 chemical species involved in 42 chemical reactions. The enzyme is represented in inactive and active forms, interconversion being promoted by activators, such as fructose 1,6-diphosphate, fructose 6-phosphate (2 molecules being required), adenosine monophosphate (both 5' and cyclical, for each of which 3 molecules are required), and inorganic phosphate (5 molecules), and inactivators such as adenosine triphosphate (3 molecules) and citrate (1 molecule). The active form is assumed to have an enzymatic mechanism similar to other kinases, the approximate K_m values for ATP and fructose 6-phosphate being about 2 x 10^-4 and 4 x 10^-5, respectively. The large numbers of activator and inhibitor molecules enable the enzyme activity to be sharply turned on and off; under appropriate circumstances it can generate pulses of product, or act as a "flip-flop" (two stable states, active and inactive). The physiological significance of these properties is discussed.

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