C. L. HOAGLAND 



bility that a deprivation of methyl groups may occur in certain diseases 

 characterized by excessive creatinuria. It has been shown that growth 

 in rats is inhibited by feeding of excess glycocyamine, and that growth 

 is resumed following the administration of choline or methionine (18). 

 Although alternative hypotheses must be entertained, the results of 

 these experiments indicate that, in the presence of an excess of sub- 

 stances which act as methyl acceptors, a loss of methyl groups may 

 occur, and that this deficiency may be prevented by an adequate intake 

 of methylating agents such as methionine and choline. Studies on 

 the total methyl output in patients with progressive muscular dystrophy 

 revealed that the loss in methyl groups, occurring as a result of exces- 

 sive creatine output, and greater than that seen in normal children, 

 was fully compensated for by a diminution in output of creatinine (7). 

 A surprising agreement was also found between the total quantity of 

 "methyl" excreted by the group of normal subjects and that excreted 

 by patients with progressive muscular dystrophy. These data suggest 

 that there is no absolute increase in the output of total creatine com- 

 pounds in progressive muscular dystrophy, and that the diseased 

 patient differs from the normal, with respect to creatine output, in the 

 differential partition of creatine and creatinine compounds in the 

 urine. In view of the fact that creatinine has been shown by isotope 

 studies to be derived from creatine, it would appear from a considera- 

 tion of these results that, in progressive muscular dystrophy, crea- 

 tinuria does not arise as a result of an increase in the synthesis of crea- 

 tine, but rather as a result of the incomplete metabolism of this material 

 in the muscle, with a consequent decrease in the amount converted to 

 creatinine. 



In view of the intimate association existing between the exo- 

 thermic decomposition of adenosine triphosphate and the integrity of 

 the contractile processes of normal muscle, no consideration of muscle 

 disease would be complete without some discussion of the metabolism 

 of this compound. Moreover, since the discovery by Lyubimova and 

 Engelhardt of the adenosinetriphosphatase activity of myosin (12), 

 speculation on the nature of myosin in muscle disease would also 

 appear to be in order. The concentration of adenosine triphosphate 

 in the muscles in progressive muscular dystrophy was found to be 

 considerably lower than in specimens of muscle taken under similar 

 conditions and from corresponding areas in normal subjects; and only 



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