Macromolecular Rate Theory (MMRT): The temperature dependence of biological rates from enzymes to ecosystems

Synopsis

We have coined the phrase “macromolecular rate theory (MMRT)” to describe the temperature dependence of enzyme-catalyzed rates. Central to MMRT is the observation that enzyme-catalyzed reactions occur with significant values of ∆Cp‡ that are in general negative. That is, the heat capacity (Cp) for the enzyme-substrate complex is generally larger than Cp for the enzyme-transition state complex. This is consistent with a classical description of enzyme catalysis whereby a negative value for ∆Cp‡ is the result of the enzyme binding relatively weakly to the substrate and very tightly to the transition state. This observation has many consequences. Firstly, Cp reports on the vibrational modes at the transition state and so we can say something about the highly controversial notion that enzyme vibrational modes contribute to catalysis. Secondly, MMRT can provide a theoretical justification for the large size of enzymes and the basis for their optimum temperatures. Under MMRT we can also rationalize the behavior of psychrophilic enzymes and describe a “psychrophilic trap” which places limits on the evolution of enzymes in low temperature environments. One of the defining characteristics of biology is catalysis of chemical reactions by enzymes and enzymes drive much of metabolism. Therefore we also expect to see characteristics of MMRT at the level of cells, whole organisms and even ecosystems.