In cells, many enzyme-catalyzed reactions are coupled as a series of biochemical steps and thus, the reaction rate is dependent on the kinetics of intermediate reaction steps. In this work, we study the case of two coupled enzymatic reactions, where the product of the first reaction serves as the substrate of the second reaction. Specifically, we examine how the maximal rate of product generation in a series of sequential reactions is dependent on the enzyme distribution and the electrostatic composition of its participant enzymes and substrates. We further quantify the extent to which the electrostatic potential increases the efficiency of transferring substrate between enzymes, which supports the existence of electrostatic channeling observed in nature. We demonstrate the interplay of these concepts in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) systems, whereby methylenetetrahydrofolate is converted via dihydrofolate to tetrahydrofolate. These findings shed light on the interplay of long-range interactions and enzyme distributions in coupled enzyme-catalyzed reactions, and their influence on signaling in biological systems. Also, the modeling from this study can be extended and applied to the multi-enzyme reaction cascade systems, which are recently developed using DNA nanotechnologies, for the rational design of efficient cascade reactions.