50 BIOCHIMICA ET BIOPHYSICA ACTA VOL. 4 (1950) 



A CONSIDERATION OF EXPERIMENTAL FACTS PERTAINING TO THE 

 PRIMARY REACTION IN MUSCULAR ACTIVITY 



by 



W. F. H. M. MOMMAERTS* 

 Department of Biochemistry, Duke University School of Medicine Durham, N. C. (U.S.A.) 



One of the most significant results of the investigations of Meyerhof and his 

 associates was the demonstration that, of all known metabolic processes the splitting 

 of adenosine triphosphate (ATP) is most directly connected with the fundamental 

 mechanical event in contracting muscle (Lohmann^''; Meyerhof^O; see^'. Chapter II). 

 Notwithstanding its importance this result is subject to two limitations. For one thing, 

 the nature of the breakdown of ATP is still not yet satisfactorily settled; the assumption 

 now popular that it is due to a straightforward hydrolysis by the enzyme myosin- 

 ATPase leads, at the present state of knowledge, to difficulties. On the other hand, the 

 introductory statement as well as Lohmann's original conclusion contained the res- 

 triction "of all known metabolic processes". It is possible that ATP, before becoming 

 decomposed, engages in other more intimate reactions with the contractile structure, 

 as will be emphasized in this paper. These restrictions do not diminish, they rather 

 enhance the emphasis on ATP, and it is exactly here that the most direct link between 

 the study of muscular metabolism and the modern analysis of its function exists. 



An essential contribution to this latter category has been made by Szent-Gyorgyi^^ 

 by his discovery of the contractility of actomyosin, his biochemical analysis of the com- 

 ponents of this complex substance, and by the study of various aspects of its behaviour. 

 This work has repeatedly been summarized in greater or lesser detail (/.c.^^. 37, 38- 27)_ 

 There are.however, a few points which may be discussed as a suitable introduction to 

 the problem of this essay. 



If ATP is indeed the ultimate action substance of muscle, as Szent-Gyorgyi in 

 logical continuation of Meyerhof's worJ< assumes, it is to be expected that addition of 

 this compound to a muscle will evoke contractions. This has been achieved. Contractions 

 were obtained by Buchthal et al.^' ^' ^ by close arterial injection of ATP, and by its 

 application to isolated muscle fibers. The latter effect was also studied in a quantitative 

 manner by Rozsa^^, using a different method. Since Buchthal finds the effect to persist 

 after curarization, it may appear difficult to assume an indirect stimulation. Never- 

 theless, the possibility that ATP in such experiments activates the excitatory process of 

 the muscle, rather than the contractile structure directly, has to be kept in mind. 

 .Rozsa's results indeed suggest this to be the case. Since the excitatory process in its 

 turn activates or liberates the ATP present, this Buchthal-Rozsa effect may play an 

 essential role in the conduction of the contraction wave. 



A simpler and more convincing system is what the writer proposes to call the fibril 

 preparation, which has been introduced by Szent-Gyorgyi^^, i, page 24. Its great 



* Established investigator of the American Heart Association. 

 References p. 56I3J. 



