V. SPECIFICITY OF ACTION 45 



identified dimethylseleiiide and measured its excretion following the ad- 

 ministration in rats of sodium selenate containing radioselenium.'-''^ 



V. specificity of Action 



WENDELL H. GRIFFITH nnd JOSEPH F. NYC 



The following discussion deals with specificity of action of choline in the 

 animal organism. Certain aspects of this problem in microorganisms are 

 included in the section on biogenesis (Section VI). 



Inasmuch as choline can be synthesized in vivo, the recognition of a 

 choline-] ike action in another compound depends in large part on whether 

 or not the compound in c^uestion is used with greater facility than choline 

 can be synthesized. The characteristic effects of choline are its role as a 

 potential source of labile methyl and its complex function as a constituent 

 of phospholipids. These properties are measured, respectively, by the rate 

 of growth of rats on diets containing homocystine but devoid of methionine 

 and by the prevention of increases of hepatic lipids in rats deprived of 

 choline. Presumably this latter property may be ascribed to phospholipids 

 such as lecithin which may also be responsible for the prevention of renal 

 lesions in young rats and of perosis in chicks and turkey poults and for 

 stimulation of growth in the young fowl. Although the specificity of choline 

 as a source of labile methyl or of phospholipid is high, it shares these proper- 

 ties to a limited extent. Pertinent data are shown in Tables III to VI which 

 are expanded from the material reported by Moyer and du Vigneaud.^ 



As indicated earlier (Section IV, p. 19), the lability of a methyl is related to 

 its attachment to a nitrogen or sulfur atom which has acquired an addi- 

 tional covalent bond and positive charge. In addition to compounds con- 

 taining preformed choline that may be liberated by hydrolysis (Ta))le III) 

 and to compounds with sulfur methyls and "onium" sulfur (Table IV), the 

 only substances known to be in this category are lietaine and dimethyl- 

 ethyl-|S-hydroxyethylammonium hydroxide or monoethylcholine (Tables 

 \ and VI). This represents a high degree of specificity, indeed, and it 

 appears that conversion to glycine betaine or to a very similar structure is 

 a prerequisite for choline activity in substances of this tj^pe. It is clearly 

 evident, however, that the presence of a methylated quaternary nitrogen 

 in betaine is not the sole factor governing specificity because l)etaincs of 



'" K. P. McConiiell and O. W. Portman. J. Biol. Chem. 195, 277 (1952). 

 ' A. W. Moyer and V. du Vigneaud, J. Biol. Chem. 143, 373 (1942). 



