NICOTINAMIDE NUCLEOTIDE ENZYMES 129 



tinamide nucleoside might take place in a fermentation system, 

 similar to the formation of cocarboxylase from thiamine. Experi- 

 ments designed to carry out such a biosynthesis of cozymase by 

 incubation with yeast preparations in the presence of phosphate 

 and adenosine phosphoric acids have not yet been successful. Never- 

 theless it can be assumed that the nicotinamide nucleoside is an 

 intermediate in the course of biosynthesis of the codehydrogenases. 



Among the lower organisms of the plant kingdom— for example, 

 Bacterium aerogenes, Torula, and other yeasts— we have examples 

 of biosynthesis of cozymase from very simple nitrogen and carbon 

 sources. Hutchens, Jandorf, and Hastings have shown recently that 

 the protozoon Chilomonas paramecium is capable of synthesizing 

 cozymase in a synthetic medium containing ammonia as the only 

 source of nitrogen and acetate as the sole source of carbon (62). 

 Other microorganisms, such as Staphylococcus aureus (54), Proteus 

 vulgaris (55), and Shigella paradysenteriae (63), require nicotinamide 

 to complete the synthesis of cozymase, a fact which permits these 

 organisms to be used for the bio-assay of nicotinamide. It has been 

 suggested that these bacteria require nicotinamide for growth as a 

 result of their parasitic existence (55). Most striking in this connec- 

 tion is the finding of Lwoff and Lwoff that Hemophilus influenzae 

 and para-influenzae require codehydrogenase I and II (41). This 

 specificity surpasses even that of man and other mammals. 



Gingrich (42) has shown that the "V" requirement of hemophihc 

 bacteria can be satisfied not only by the oxidized codehydrogenases 

 but also by dihydrocozymase, acid-treated dihydrocozymase (com- 

 pletely inactive as codehydrogenase), and desamino cozymase, an 

 artificial derivative of cozymase (61) in which the adenylic acid is 

 replaced by inosinic acid. Furthermore, the fact that the nicotinam- 

 ide nucleoside has been found (42) to promote the growth of these 

 organisms is highly interesting in that it demonstrates that the only 

 special requirement is the preformed linkage of nicotinamide to the 

 pentose. It is obvious, then, that the nutrihtes required for the 

 biosynthesis of cozymase are related chiefly to the nicotinamide 

 moiety and its linkage to the rest of the molecule. The steps in 

 biosynthesis between simple nitrogen and carbon compounds and 

 the pyridine ring remain a promising field of investigation. 



REFERENCES 



1. a) Thunberg, T., Ergebnisse d. Enzymforschung ( Nord-Weidenhagen ) , 

 7, 163 (1938). 



