Modular control analysis of slipping enzymes

A theory is developed that deals with the metabolic control exerted by enzymes that catalyze two or more, incompletely coupled reactions. The starting point is modular (top-down) metabolic control theory. Slipping enzymes are considered as modules with more than one independent flux. Control by the coupled reaction is distinguished quantitatively from control by the extent of slippage. This is achieved by appropriate linear transformation of fluxes or logarithms thereof. Different transformations are proposed and discussed. Our examples include free-energy transducing proton pumps and the Na+, K+-ATPase. It is shown that control coefficients can be calculated on the basis of a description of slipping enzymes in terms of linear non-equilibrium thermodynamics. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.