XI. PHARMACOLOGY 127 



appears rapidly from the blood stream-'^ but does not increase appreciably 

 the amount in the urine.-''"-^ 



When Luecke and Pearson'-" fed large doses of choline chloride (10, 20 

 and 40 g. to sheep and 5 g. to dogs), no significant increase resulted in the 

 free or total choline in plasma, liver, or kidney and only a very small 

 fraction (0.5 to 2.5%) was recovered in the urine (24-hour collection). 

 Before treatment normal sheep excreted in the urine about 2 mg. of choline 

 per 24 hours; after 40 g. daily for a period of 6 days the output increased 

 significantly to between 300 and 500 mg. daily in one animal and to be- 

 tween GOO and 1050 mg. in the other (0.7 to 2.5 % of the intake). Johnson 

 et alr'^ found that equally small proportions (0.7 to 1.5%) of the choline 

 intake were excreted as such in the urine by human subjects. 



Choline is not destroyed by blood in vitro. ^^ The destruction probably 

 occurs largely in the li^'er. In some species (rat and hamster, but not guinea 

 pig) a specific enzyme, choline oxidase, is found in the liver and kidney-^ • ^° 

 which oxidizes the alcohol group to give betaine aldehyde. A second enzyme 

 continues the oxidation to betaine. Only negligible amounts of choline, 

 trimethjdamine, or its oxide could be found in the urine of a large dog 

 given 20 g. of choline chloride during a 6-day period. ^^ Possibly the methyl 

 groups are oxidized in some species by another enzyme via formic acid to 

 CO 2 and water. 



The methyl groups of choline appeared to be labile in certain physiologi- 

 cal environments, but recent studies suggest that they become labile only 

 after conversion to compounds such as betaine aldehyde or betaine.-'*-"^'* 



Popper^^' -^^ has reported that in normal human beings about two-thirds 

 of orally administered doses of choline chloride appear in the urine as 

 trimethylamine (mainly in the form of its oxide). Since the proportion so 

 excreted is greatly reduced after treatment of the patient with antibiotics 

 and is even smaller when the choline chloride is administered intravenously, 



2^ R. Hunt, ./. Pharmacol. Exptl. Therap. 7, .301-337 (1915). 



25 M. Guggenheim and W. Loffler, Biochem. Z. 74, 208-218 (1916). 



26 R. W. Luecke and P. B. Pearson, /. Biol. Chem. 158, 561-566 (1945). 



" B. C. Johnson, T. S. Hamilton, and H. H. Mitchell, J. Biol. Chem. 159, 5-8 (1945). 



28 F. Wrede, E. Strack, and PJ. Bornliofen, Hoppe-Seylcr's Z. physiol. Chem. 183, 

 123-132 (1929). 



29 F. Bernheim and M. L. C. liernheim. Am. .J . Physiol. 104, 438-440 (1933). 



30 F. Bernheim and M. L. C. Bernheim, Am. J. Physiol. 121, 55-60 (1938). 

 " H. Fuchs, Z. Biol. 98, 473-478 (1938). 



32 J. W. Dulinoff, Federation Proc. 8, 195 (1949) 



33 J. W. Duhnofr, Arch. Biochem. 24, 251-262 (1949). 



34 J. A. Muntz, ./. Biol. Chem. 182, 48!) 499 (19.50). 



35 H. Popper, in Discussion, Trans. 10th Conf. Liver Injury, New York (1951). 



36 J. de la Huerga and II. Popper, J. Clin. Invest. 30, 463-470 (1951). 



