502 NIACIN 



It is also clear that the pyridine nucleotides are indirectly important in 

 fatty oxidation, since the 2-carbon activated acetyl compounds which re- 

 sult from the /3-oxidation of fatty acids are further oxidized via the tricar- 

 boxylic acid cycle. These substances enter the cycle principally by condens- 

 ing with oxalacetic acid to form citric acid. Furthermore, these acetyl 

 compounds seem to provide the common link between fat and carbohy- 

 drate metabolism. Since they can be formed from either carbohydrate or 

 fat, they provide a means of synthesis of fat from carbohydrates or, vice 

 versa, the oxidation of fat to provide energy. 



Lehninger^^^ has shown that DPN is required for fatty acid oxidation in 

 crude rat liver homogenates. Green and associates^" also have demonstrated 

 fatty acid oxidation in enzyme systems which require DPN or TPN. The 

 exact reactions and mechanisms involved in these complex systems and 

 the specific role of the pyridine nucleotides (other than as a means of gen- 

 erating high-energy phosphate) is completely unknown. 



The DPN requirement for fatty acid synthesis is even less clear. How- 

 ever, it is thought that fatty acid synthesis and degradation proceed through 

 identical, albeit reverse, reaction pathways. On this basis, DPN-TPN 

 would undoubtedly be required. Eakin^^ believes that the pyridine nucleo- 

 tides are required for the numerous dehydrogenations which are probably 

 involved and has proposed a scheme based on known reactions, some of 

 which are DPN-linked, which could account for the synthesis of fatty acids. 



DPN is important in the metabolism of the ketone bodies, since the 

 interconversion of L-/3-hydroxybutyric and acetoacetic acids is hnked to 

 this coenzyme.^"' "* 



H 



OHO OHO 



I I II II I II 



H3C— C— C— C— OH + DPN ^ H3C— C— C— C— OH + DPNH2 



I I I 



H H H 



6. In Nitrogen Metabolism 



The pyridine nucleotides play a direct role in the metabolism of amino 

 acids in only one system. Either DPN or TPN is required for the reversible 

 oxidative deamination of L-glutamic acid. The a-amino group is converted 

 to an a-imino group which spontaneously hydrolyzes to yield NH3 and 

 a-ketoglutaric acid. Since this reaction is reversible, it provides a link for 

 the biological synthesis of an amino acid utilizing inorganic ammonia and 

 a compound which can be derived from carbohydrate. Conversely it pro- 



»6 A. L. Lehninger, J. Biol. Chem. 161, 437 (1945). 



1" D. E. Green and J. Brosteaux, Biochem. J. 30, 1489 (1936). 



138 D. E. Green, J. G. Dewan, and L. F. Leloir, Biochem. J. 31, 934 (1937). 



