IV. BIOCHEMICAL SYSTEMS 513 



N. TISSUE DISTRIBUTION AND FATE 



The tissue distribution and intermediary metabolism of administered 

 nicotinic acid has been poorly understood. Some studies have been done 

 measuring changes in tissue concentration and urinary ex(a-etion following 

 administration of the vitamin. Although such studies are valuable, they 

 are limited by their inability to distinguish the distribution and fate of 

 administered \itamins in relation to pre-existing tissue stores. 



1. Excretion 



Roth and associates'^"^ have applied radioactive tracer techniques to this 

 problem with very interesting results. They administered C'^-carboxyl- 

 labeled nicotinic acid and nicotinamide intraperitoneally to mice and de- 

 termined radioactivity in exhaled air, urine, feces, and tissues as a function 

 of time. 



A single dose of nicotinic acid, 0.7 mg., which is considerably in excess 

 of the normal daily requirement, resulted in a large excretion of radioac- 

 tivity in urine (about 60 % of administered dose) and in pulmonary carbon 

 dioxide (about 3 % of administered dose) within the first 24 hours. The latter 

 finding is of especial interest, since it proved, for the first time, that animal 

 tissues are capable of decarboxylating nicotinic acid. The rather large 

 urinary excretion would be expected, since the animals were, presumably, 

 alreadj^ well nourished with respect to nicotinic acid. Excretion was much 

 less after 24 hours, and minimal after 48 hours. Nicotinic acid remaining 

 in the animal at this point was assumed to be a part of the normal tissue 

 enzyme stores. By comparing the amount of radioactivity excreted in 

 urine and in pulmonary carbon dioxide after 48 hours, these investigators 

 estimated that the mouse normally disposes of 15 to 20 % of the nicotinic 

 acid liberated from the tissues as carbon dioxide. Since only the carboxyl 

 group of the administered nicotinic acid was labeled, this does not neces- 

 sarily mean that the pyridine ring was also oxidized to carbon dioxide. 

 In later studies' ^^ these investigators showed that this phenomenon of 

 pulmonary carbon dioxide excretion from labeled nicotinic acid and nico- 

 tinamide also existed in hamsters, rats, and dogs. Hamsters and rats ex- 

 creted somewhat more in this fashion, and dogs much less than the mouse. 

 Very little, if any, of the radioactivity appeared in the feces, a fact of 

 significance in the problem of intestinal synthesis of nicotinic acid (p. 530). 



»«* L. J. Roth, E. Leifer, J. R. Hogness, and W. H. Langham, /. Biol. Chem. 176, 249 



(1948). 

 •" E. Leifer, L. J. Roth, D. S. Hogness, and M. 11. Corson, /. Biol. Chem. 190, 595 



(1951). 



