Metabolic control analysis of moiety-conserved cycles.

Moiety-conserved cycles are metabolic structures that interconvert different forms of a chemical moiety (such as ATP-ADP-AMP, the different forms of adenylate), while the sum of these forms remains constant. Their metabolic behaviour is treated within the framework of control analysis [Kacser, H. & Burns, J.A. (1973) Symp. Soc. Exp. Biol 27, 65-104]. To explain the importance of the conserved sum of cycle metabolites as a parameter of the system, the cycle is first regarded as a 'black box'. The interactions of the cycle with the rest of the system are expressed in terms of 'cycle elasticities' and 'cycle control coefficients' by the usual connectivity properties. The conserved sum is seen to be an 'external' parameter in the sense that its effect is described by a combined response expression. All cycle coefficients can be written in terms of elasticities and concentrations of cycle metabolites. The treatment shows how connectivity expressions should be modified when moiety-conserved cycles are present and establishes new summation and connectivity properties. The analysis is applied to a two-member moiety-conserved cycle and its general application is discussed.