Falling Enzyme Activity as Temperature Rises: Negative Activation Energy or Denaturation?

Recently in this Journal, Aledo and coworkers used the Michaelis-Menten and Arrhenius equations to show that, under the biologically common condition of low substrate concentration, reaction rates can actually decline with increasing temperature. They presented two data sets showing a decline in lactate dehydrogenase activity above 20-30 degrees C as an example of this behavior. Although denaturation provides a fairly good statistical fit to the lactate dehydrogenase data sets, it is exceedingly unlikely that the activity decline above 20-30 degrees C is caused by denaturation. Instead, it is possible that a dramatic conformational change of the enzyme occurs in this temperature range, causing the apparent activation energy to shift from positive to negative and the frequency factor to fall by over 4 orders of magnitude. This conformational change is intriguing and worthy of further study.