The control equations can also be derived in a more rigorous fashion using the systems equation:
where  is the stoichiometry matrix,  is a vector of chemical species, and  is a vector of parameters (or inputs) that can influence the system. In metabolic control analysis the key parameters are the enzyme concentrations. This approach was popularized by Heinrich, Rapoport, and Rapoport and Reder and Mazat. A detailed discussion of this approach can be found in Heinrich & Schuster and Hofmeyr.