IV. BIOCHEMICAL SYSTEMS 517 



feeding thyroglobulin, but methionine or choline tended to bring the urinary 

 levels back to normal. Vitamin B12 may also be involved in the methylation 

 of nicotinamide, probably through its influence on the synthesis and trans- 

 fer of labile methyl groups.^'^ 



V. Specificity of Action 



J. M. HUNDLEY 



A. MODIFICATIONS OF THE NICOTINIC ACID MOLECULE 



Many substances related chemically to nicotinic acid have been tested 

 for their ability to replace this vitamin in mammalian nutrition. Table XI 

 represents a partial compilation of such compounds. The following con- 

 clusions may be drawn concerning the range within which the molecule 

 may be modified and still retain biological activity. 



1 . The pyridine molecule must have a substituent group in the 3 position. 



O 



2. This substituent group must be a derivative of — C — R. Molecules 

 with other groups on the 3 position such as CHs, NHo or CN have no, or 

 much less, biological effectiveness, presumably because they must be con- 



O 



verted to the — C — grouping. 



3. The R group attached to the 3-carboxyl may be any one of a great 

 number of compounds and types such as esters and N-substituted amides 

 and still retain biological effectiveness. 



O 



II 



4. Substitution of an acetyl (C — CH3) for the 3-carboxyl group leads to a 



compound (3-acetylpyridine) which is a nicotinic acid antagonist under 

 certain conditions^'* but can be converted to nicotinic acid under other con- 

 ditions.-^ 



211 I. E. Liener and M. O. Schultze, /. Nutrition 46, 223 (1952). 



1 P. J. Fouts, O. M. Helmer, S. Lepkovsky, and T. H. Jukes, Proc. Soc. Exptl. Biol. 

 Med. 37, 405 (1937). 



2 P. Ellinger, G. Fraenkel, and M. M. Abdel Kader, Biochem. J. 41, 559 (1947). 



3 V. A. Najjar and L. E. Holt, Jr., Proc. Soc. Exptl. Biol. Med. 48, 413 (1941). 

 ■* P. Ellinger and R. A. Coulson, Biochem. J. 38, 265 (1944). 



5 W. A. Krehl, P. S. Sarma, L. J. Teply, and C. A. Elvchjem, ./. Nutrition 31, 85 

 (1946). 



6 D. W. Woolley, F. M. Strong, R. J. Madden, and C. A. Elvehjem, J. Biol. Chem. 

 124, 715 (1938). 



