The Mechanochemistry of Muscular Contraction

The dependence of PC a and ATP 1 dephosphorylation on the number of isometric twitches in the iodoacetate-nitrogen-poisoned muscle has been examined. There is no net dephosphorylation of adenosinetriphosphate. PC dephosphorylation varies linearly with the number of twitches and produces equivalent amounts of C a and p~.l Iodoacetate concentrations which block the enzyme, creatine phosphokinase, render the muscle non-contractile. A value of 0.286/zmole/gm. for the amount of PC split per twitch is obtained which gives a value of --9.62 kcal . /mole for the "physiological" heat of hydrolysis of PC in agreement with expectations based on thermochemical data. In a single maximal isometric twitch it is estimated that 2 to 3 PC molecules are dephosphorylated per myosin molecule, or 1 per actin molecule. The results support the view that under the conditions of these experiments PC dephosphorylation is the net energy yielding reaction. The in vivo stoichiometry of the mechanochemistry of contraction revealed by these studies on the one hand, and the known stoichiometry of actin polymerization and its coupling to the creatine phosphokinase system on the other are strikingly similar and strongly suggest that the reversible polymerization of actin is involved in a major way in the contraction-relaxation-recovery cycle of muscle. T h e work of L u n d s g a a r d (1930a, b), L o h m a n (1934), E n g e l h a r d t and L jub i m o v a (1939) laid the f o u n d a t i o n for the n o w classical v iew tha t adenos ine t r i phospha t e a n d p h o s p h o c r e a t i n e a re the p r i m a r y and seconda ry ene rgy sources, respect ively, for m u s c u l a r con t rac t ion . Studies on ac tomyos in th reads and g lyce r ina ted models b y A. S z e n t G y o r g y i (1949) and his col leagues, a n d The research reported here was supported by funds provided under United States Public Health Service Grant RB-3723. Received for publication, February 29, 1960. 1 The following abbreviations will be used here: ATP for adenosinetriphosphate, ADP for adenosinediphosphate, PC for N-phosphoryl creatine, C for creatine, CPT for creatine phosphoryltranferase, Pi for orthophosphate, IAA for iodoacetic acid.