When both K_m and V_max are altered, Is the enzyme inhibited or activated?

Enzyme activators lower K_m (the Michaelis constant) and/or raise V_max (the asymptotic reaction velocity at infinite substrate concentration); conversely, inhibitors raise K_m and/or lower V_max . But what if an effector moves both K_m and V_max in the same direction? Uncompetitive inhibitors, which decrease both K_m and V_max by the same factor, are the most common example of this. A less well-known example occurs often when crowding agents are added to the buffer in order to mimic the environment commonly encountered in vivo. Crowding agents tested on different enzymes have been shown to have every conceivable effect on K_m or V_max , causing them to rise, fall, or stay the same. In this article, a mathematical analysis is presented allowing biochemists to judge whether an effector that causes K_m and V_max to both move in the same direction serves as an inhibitor, an activator, or most surprising, as both. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):446-449, 2019.