Control of the metabolic flux in the system with high enzyme concentrations and moiety-conserved cycles: the sum of the flux control coefficients can drop significantly below unity

Kholodenko B.N., __Lyubarev A.E.__, Kurganov B.I.

*Eur. J. Biochem.*, 1992, v. 210, p. 147-153

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In a number of metabolic pathways enzyme concentrations are comparable to those of substrates. Recently it has been shown that many statements of the 'classical' metabolic control theory are violated if such a system contains a moiety-conserved cycle. For arbitrary pathways we have found: (a) the equation connecting coefficients C_{Ei}^{J} (obtained by varying the E_{i} concentration) and C_{vi}^{J} (obtained by varying the kicat), and (b) modified summation equations. The sum of the enzyme control coefficients (equal to unity under the 'classical' theory) appears always to be below unity in the systems considered. The relationships revealed were illustrated by a numerical example where the sum of coefficients C_{Ei}^{J} reached negative values. A method for experimental measurements of the above coefficients is proposed.