Mechanism of ATP hydrolysis

Abstract

In searching for the molecular basis of contraction we need to relate chemical events with mechanical events. These must be quantitatively coupled in their extent (thermodynamics) and time course (kinetics). Unfortunately, chemical kinetic analysis of muscle itself presents practical and theoretical difficulties. In a muscle fibre the interaction sites are not freely diffusable and therefore do not combine by a simple bimolecular process. Also, once bound, the rates of subsequent steps depend on the tension borne by the filaments. Isolated proteins, on the other hand, form homogeneous solutions of defined concentration and their reactions may be initiated and terminated rapidly. Solution studies provide a basis for elucidating the catalytic mechanism of ATP hydrolysis and actin activation. Measurement under steady-state conditions reveal a correlation between the velocity of shortening of different muscle types and the ATPase rate of the actomyosin extracted from them (e.g. fast-twitch muscles have a high ATPase activity). However, our understanding of this correlation has been advanced through the application of transient kinetic techniques.