Kacser and Burns introduced an additional coefficient that described how a biochemical pathway would respond the external environment. They termed this coefficient the response coefficient and designated it using the symbol R. The response coefficient is an important metric because it can be used to assess how much a nutrient or perhaps more important, how a drug can influence a pathway. This coefficient is therefore highly relevant to the pharmaceutical industry.
The response coefficient is related to the core of metabolic control analysis via the response coefficient theorem, which is stated as follows:
where  is a chosen observable such as a flux or metabolite concentration,  is the step that the external factor targets,  is the control coefficient of the target steps, and  is the elasticity of the target step with respect to the external factor .
The key observation of this theorem is that an external factor such as a therapeutic drug, acts on the organism's phenotype via two influences: 1) How well the drug can affect the target itself through effective binding of the drug to the target protein and its effect on the protein activity. This effectiveness is described by the elasticity  and 2) How well do modifications of the target influence the phenotype by transmission of the perturbation to the rest of the network. This is indicated by the control coefficient .
A drug action, or any external factor, is most effective when both these factors are strong. For example, a drug might be very effective at changing the activity of its target protein, however if that perturbation in protein activity is unable to be transmitted to the final phenotype then the effectiveness of the drug is greatly diminished.
If a drug or external factor, , targets multiple sites of action, for example  sites, then the overall response in a phenotypic factor , is the sum of the individual responses: