678 THE SEAT OF FORMATION OF UREA 



kreatin, presumably because it contains the necessary methylated 

 N. It would be possible, therefore, to look upon kreatin as a 

 normal metabolite of muscle proteid which resisted further change 

 in the body excepting dehydration ; and if it could be shown that 

 kreatin possesses a physiological action, it might explain why such 

 comparatively small quantities of kreatin should leave the body. 

 Again, there is the further possibility that kreatin is a substance 

 developed de novo, like adrenalin, in muscle by synthesis of 

 guanidin in order that it may exert a physiological action. It has 

 been shown that it increases the irritability of the motor nerve 

 endings, and guanidin that of the muscle fibres. It seems possible 

 that when the nerve impulse reaches a muscle it may set up 

 chemical changes there with the production of substances which 

 increase the excitability of nerve and muscle. Such considerations 

 raise a doubt whether it is necessary to believe that endogenous 

 kreatin does leave muscle as something other than kreatin and is 

 a precursor of urea. 



THE SEAT OF FORMATION OF UREA 



That portion of urea which is produced direct from arginin 

 must have its seat of formation limited to the distribution of 

 arginase. This ferment has been found in the liver, kidneys, 

 thymus, lymphatic glands, and mucous membrane of the alimentary 

 canal ; it is absent from the spleen and suprarenals, and, most 

 significantly of all, the muscles. 



We have now to deal with the seat of production of urea 

 from ammonium compounds. It might have been expected that 

 organs which are the seat of urea formation would contain on 

 analysis more urea than those in which no such formation was 

 taking place. Many of the older analyses have shown that the 

 liver contained more urea than other organs. Schondorff was 

 unable to confirm this. In the case of a dog fed on meat, he 

 found that the blood and all the other organs, including the liver, 

 contained the same percentage of urea, namely, 0*12 per cent. 

 There were only two marked exceptions; the muscles with 0'08 

 per cent., which was less than the blood, and the kidneys with 0'67 

 per cent., which was much higher, and probably to be accounted 

 for their being the seat of excretion. Schroder was the first 

 observer who made a systematic "experimental investigation of the 



