THE RATE OF THE GLUCOKINASE REACTION IS CONTROLLED BY ITS ELEMENTAL STEPS

The limitation of an enzymic reaction by its elemental steps is charac terized quantitatively by the so-called ''control coefficients'' of th e steady-state rate of this reaction. The old paradigm of the limiting step is shown to be inapplicable to the description of the control of the rate of the glucokinase reaction. The control of the flux is dist ributed between several elemental steps (ATP binding, ADP release, etc .). This distribution changes significantly on varying the conditions, particularly the glucose and ATP concentrations. At similar to 1 mM A TP and 2-5 mM glucose, the contribution of the step of ATP binding to the control of the total flux is positive, exceeding 50% when ATP is b ound after glucose. Conversely, if the binding of ATP precedes that of glucose, the control coefficient for ATP binding is negative. At high concentrations of the substrates, the contribution of the steps of pr oduct dissociation to the flux control becomes significant. It is also shown that the distribution of the control between the elemental step s cannot be predicted from their corresponding values of the maximum c hange of the Gibbs energy or the minimum rate constant.