480 NIACIN 



IV. Biochemical Systems 



J. M. HUNDLEY 



A. INTRODUCTION 



Like most other B vitamins, nicotinic acid (or a derivative) is recjuired 

 by all living cells. It is an essential part of certain coenzymes which cata- 

 lyze chemical reactions essential to cellular life. So far as is known, nico- 

 tinic acid has no metabolic function other than that exerted through the 

 coenzymes of which it is a part. 



Actually, specific biochemical functions for nicotinic acid were discovered 

 before it was known that this substance was a vitamin. In 1934 Warburg 

 and Christian^ • - found that nicotinamide Avas part of the coenzyme II 

 molecule. The following year nicotinamide was isolated from cozymase 

 (coenzyme I) by von Euler and associates^ and later by Warburg and 

 Christian.'* It was not until 1937, when Elvehjem et al.^ discovered that 

 nicotinic acid would cure blacktongue in dogs and the subsequent finding 

 that it would cure pellagra in man, (see p. 453) that the full biological 

 significance of this simple organic molecule was realized. Since these pioneer 

 discoveries more than forty biochemical reactions have been identified 

 which are dependent on these two coenzymes. More reactions will likely be 

 discovered. Most of these reactions have been studied in great detail. Much 

 exact information is available on the mechanism and kinetics of the reac- 

 tions, on the effect of environmental influences, and on the interdependence 

 of these with other biochemical reactions. 



However, it is important to remember that most of the detailed informa- 

 tion on coenzyme I and II catalyzed reactions has been obtained from 

 in vitro studies using simplified enzyme systems. It is well known that 

 these reactions are only steps in the very complex series of reactions which 

 occur in the intact cell. There are undoubtedly many influences in the 

 intact cell which modify the reactions observed in simplified systems. The 

 in vivo consequences of blocking or impeding specific biochemical steps, the 

 ability or inability to activate alternate reaction pathways, and effects due 

 to the accumulation of substrate or abnormal metabolites are only examples 

 of the complexities involved in evaluating the biochemical function of nico- 

 tinic acid in intact organisms. This field has hardly been explored. 



' O. Warburg and W. Christian, Biochem. Z. 274, 112 (1934). 



2 O. Warburg and W. Christian, Biochem. Z. 275, 112, 464 (1935). 



3 H. von Euler, H. Albers, and F. Schlenk, Hoppe-Seyler's Z. physiol. Chem. 237, 

 180 I (1935); 240, 113 (19.36). 



^ O. Warburg and W. Christian, Biochem. Z. 287, 291 (1936). 



5 C. A. Elvehjem, R. J. Madden, F. M. Strong, and D. W. Woolley, /. Am. Chem. 

 Soc. 59, 1767 (1937); /. Biol. Chem. 123, 137 (1938). 



