Energetics of Myosin ATP Hydrolysis by Calorimetry
For over ten years from the mid-1970s, ATP hydrolysis into ADP and inorganic phosphate (P i ) by myosin were investigated by reaction calorimetry using own-designed instruments. The purpose was to estimate enthalpy changes for intermediate steps of the hydrolysis cycle. The results indicated that the steps are accompanied by large enthalpy changes alternating between negative and positive values. By combining this enthalpic profile with Gibbs energy changes for the corresponding steps estimated by kinetics and equilibrium analysis, the overall energetic profile of the ATP hydrolysis cycle has been revealed. The most characteristic feature is that all the intermediates are near the same Gibbs energy levels (isoenergetic); this occurs because large enthalpy and entropy changes compensate each other in the bound ATP-hydrolyzing and subsequent P i -releasing steps. Possible sources of the large entropy changes were investigated in the late 1990s using dielectric spectroscopy to measure changes in hydration level of myosin during the ATP hydrolysis cycle. The result indicated dehydration during the hydrolysis step and rehydration during the P i -releasing step. The extent of these hydration changes on the myosin molecular surface was just sufficient to account for their observed entropy changes. Taken together, once myosin traps ATP, the system is brought into a low-entropy state that is maintained until hydrolysis products, P i and ADP are released from myosin. Thus, ATP plays the role of mediator to bring negative entropy into the function of the myosin.
KeywordsMuscle Gibbs energy Enthalpy Entropy Hydration and dehydration
I am grateful to Nancy A. Curtin, Professor Emeritus of Imperial College London, for critical reading of the manuscript and for many useful suggestions. I would also like to express my sincere gratitude to Makoto Suzuki, Professor Emeritus of Tohoku University, for his collaboration with me over the past two decades. Finally, this chapter is dedicated to the memory of Roger C. Woledge.
- Curtin N, Rosenberg M (2006) An interview with Roger Woledge. http://www.physoc.org/sites/default/files/page/Roger_Woledge_0.pdf
- Gutfreund H (1995) Thermodynamic information from kinetics. In: Kinetics for the life sciences: receptors, transmitters and catalysts. Chapter 4 kinetic analysis of complex reactions. Cambridge University Press, Cambridge, UK/New York, pp 110. ISBN: 978-0521485869Google Scholar
- Kodama T, Kometani K (1986) A stopped-flow calorimetric study of ATP hydrolysis by myosin subfragment 1. Proc Japan Acad 62B:105–108Google Scholar
- Ricchiuti NV, Mommaerts WFHM (1965) Technique for myothermic measurements. Physiologist 8:259Google Scholar
- Schrödinger E (1944) It feeds on ‘negative entropy’. In: What is life—the physical aspect of the living cell. Chapter 6 order, disorder and entropy. Cambridge University Press, Cambridge, UK, pp 68–75. http://dlab.clemson.edu/11._Erwin_Schrodinger_-_What_is_Life__1944_.pdf
- Woledge RC (1972) Heat, work and phosphocreatine splitting during muscular contraction. Cold Spring Harb Symp 37:613–618Google Scholar
- Woledge RC (1976) Calorimetric studies of muscle and muscle proteins. In: Lamprecht I, Saarschmidt R (eds) Application of calorimetry in life sciences. Proceedings of the international conference in Berlin, August 2–3, 1976. de Gruyter, Berlin, pp 183–197. ISBN: 3110069199Google Scholar