590 



SCIENCE 



[N. S. Vol. XXIX. No. 745 



growth or atrophic changes. In view of the 

 growing mass of data on the fate of ingested 

 creatin and creatinin there is an unfortunate 

 paucity of information regarding the changes 

 which they experience after parenteral intro- 

 duction into the body, where the uncertainties 

 of change or loss in the alimentary tract are 

 obviated and exact dosage becomes a possi- 

 bility. The tendency to relegate important 

 metabolic functions to the liver points to the 

 desirability of studies on the fate of the ni- 

 trogenous katabolites in animals in which the 

 hepatic functions have been excluded. In the 

 only reference which I have found on this 

 point, creatin was reported in noteworthy 

 amounts in the urine of a dog after the Eck 

 fistula operation and further extirpation of 

 the liver (Salaskin and Zaleski). 



The questions raised by the discussions re- 

 garding the intervention of enzymatic proc- 

 esses are timely and preeminently significant. 

 Here, however, the limitations of the present 

 colorimetric method are most likely to impede 

 satisfactory progress and they invite the con- 

 sideration of the analyst. The nature of the 

 relation between inanition and excretion of 

 creatin must be analyzed into its possibilities. 

 Are we dealing with a general depression of 

 katabolic organs in inanition? Or is the 

 absence of metabolizable energy-yielding prod- 

 ucts in the tissues the sole factor? These 

 questions are being investigated at present in 

 our own laboratory. The behavior of the cre- 

 atin bodies in the presence of microorganisms 

 of the alimentary tract likewise deserves study, 

 especially in view of the constant finding of 

 methylguanidin among the products of bac- 

 terial action on creatin (Nawiasky), and of 

 methylguanidin and dimethylguanidin in the 

 urine (Achelis). 



One can not conclude this topic without 

 reference to the possible nitrogenous precurs- 

 ors of creatin and creatinin in the body. 

 Speculation has been rife and claims have 

 been numerous. That protein feeding does 

 not per se increase the output in the urine has 

 been conclusively demonstrated. Experiments 

 with nucleic acid compounds (with thymus 

 glands) which yield purin and pyrimidin 

 derivatives structurally similar to creatinin, 



have had a negative outcome (Burian; Jaffe; 

 Dorner; Lefmann). 



HN- 



-CO 



(CH3)N CHj 



creatinin 



HN CO 



0=0 C 



HN- 



H 



1!h 



The exi)erience with methylguanidin and 

 with glycocyamin (guanidin acetic acid) is 

 negative or uncertain at best (Jaffe; Corner; 

 Achelis). W. Koch's hypothesis relating cre- 

 atinin to the metabolic change of methyl 

 groups in the body and connecting it with the 

 metabolism of the phosphatide (lecithin and 

 kephalin) remains an interesting but unveri- 

 fied assumption. The guanidin derivate 

 arginin stands structurally in close relation 

 to creatin; while histidin, with its imidazole 

 structure presents little more than analogy. 



NH2 



HN: 



(CHa)N— CHj.COOH 

 creatin 



NHj 



I 

 HN=C 



HN— CH, . CH, . CH, . CH ( NH. ) COOH 

 arginin 



HN CH 



N C— CH,.CH(NH,) .COOH 



histidin 



With neither of these compounds have experi- 

 mental relations to creatin and creatinin been 

 established. The nature of their synthesis 

 still remains within the realms of surmise, 

 inviting the organic chemist, as has so often 

 been the case in biology, to supplement the 

 efforts of the physiologist. 



Lafayette B. Mendel 

 Yale University 



