508 NIACIN 



are disrupted so that special precautions must be taken when making ho- 

 mogenates or extracts of tissue for DPN or TPN analysis. 



The extent to which these "destroying" mechanisms may have physio- 

 logical significance in the normal wear-and-tear breakdown of the pyridine 

 nucleotides is unknown. It is of considerable interest, however, that Zat- 

 man^''- has recently used isotopic nicotinamide to demonstrate that spleen 

 DPNase catalyzes an exchange between free nicotinamide and that bound 

 into DPN. This provides a mechanism whereby the nicotinamide can be 

 removed and replaced in DPN-TPN without destruction of the rest of the 

 molecule. 



L. INHIBITORS OF DPN AND TPN 



Inhibitors in intact animals are considered elsewhere (p. 548). 



Inhibitors such as cyanide and iodoacetate are known to inhibit some 

 codehydrogenase enzyme systems in vitro. Of potentially greater biological 

 significance is the fact that at least some DPN-TPN-hnked systems can 

 be inhibited by the components of the DPN molecule. The inhibitory effect 

 of nicotinamide on DPN breakdown has already been mentioned (p. 507). 

 Feigelson et al}"^^ have shown that high levels of nicotinamide inhibit the 

 respiration of rat liver homogenates, an effect reversible with DPN. From 

 an analysis of the Michaelis constants they believe this to be due to a com- 

 petition between nicotinamide and DPN for the apoenzyme. However, 

 Adler et al}"^^ believe that this phenomenon is more complicated than just 

 enzyme displacement. They found that pyridine-3 -sulfonic acid (a nicotinic 

 acid inhibitor in bacteria) would inhibit glucose and lactic dehydrogenase 

 systems, but so would salicylic acid, nicotinic acid, adenine, adenosine, 

 and adenine dinucleotide. Inhibition could be reversed with DPN but not 

 by adenine compounds. In addition, succinic dehydrase, which is not DPN- 

 linked, was also inhibited by the compounds listed above. Williams^^^ re- 

 cently reported that adenine, adenosine, and adenosinetriphosphate would 

 inhibit a malic dehydrogenase system in a manner competitive with DPN. 

 Sulfathiazole and sulfapyridine have been reported to inhibit nicotinamide- 

 stimulated respiration and growth in certain microorganisms. ^^^ However, 

 Anderson and associates'^^^ found no effect of these sulfa drugs on DPN- 



1" L. J. Zatman, Federation Proc. 11, 315 (1952). 



1" P. Feigelson, J. N. Williams, and C. A. Elvehjem, /. Biol. Chem. 189, 361 (1951). 



"^ E. Adler, H. von Euler, and B. Skarzynski, Arkiv Kemi, Mineral. Geol. 16A, No. 



9, 1, (1943); 17, No. 2, 1 (1943). 

 1" J. N. Williams, Jr., J. Biol. Chem. 195, 629 (1952). 

 i'6 R. West and A. F. Cobm-n, /. Exptl. Med. 72, 91 (1940). 

 "^ E, G. Anderson, F. J. Pilgrim, and C. A. Elvehjem, Proc. Soc. Exptl. Biol. Med. 



55, 39 (1944). 



