In contrast to the flux summation theorem, the concentration summation theorem sums to zero. The implications of this are that some enzymes will cause a given metabolite to increase while others, in order to satisfy the summation to zero, must cause the same metabolite to decrease. This is particularly noticeable in a linear chain of enzyme reactions where, given a metabolite located in the center of the pathway, an increase in expression of any enzyme upstream of the metabolite will cause the metabolite to increase in concentration. In contrast, an increase in expression of any enzyme downstream of the metabolite will cause the given metabolite to decrease in concentration.