NUCLEOTIDES AND COENZYMES 



Nucleotides are then formed by specific ATP-kinases, e.g., 



adenosine + ATP > AMP + ADP (10) 



or, directly from the base by the reaction (28) : 



adenine + l-pyrophosphoryI-ribose-5-phosphate > AMP + PP 



(11) 



Dinucleotides are formed from the corresponding mononucleo- 

 tides by the representative reaction : 



FMN + ATP > FAD + PP (12) 



where the ATP donates its nucleoside portion {cf. also the syn- 

 thesis of active methionine) instead of a phosphate as in equation 

 (4), and additional phosphates are supplied to the dinucleotide 

 (as in TPN and CoA) by another ATP-kinase reaction : 



DPN + ATP > TPN + ADP (13) 



The entire biosynthetic route to CoA has been established 

 by Lipmann and Novelli (33) and by Snell and colleagues (8), 

 and is reproduced in the scheme below, since it illustrates many 

 of the above principles. 



ATP ADP 

 Pontothenote + Cysteine ►N-Pontothenyl cysteine 



ATP 



AT^__ADP .C02 ^^^ 



Pantetheine »4-PhosphopQntotheine"« — 4-Phosphopantothenyl cysteine 



ATPx 



PP ' 



I ATP ADP 



Dephospho CoA ►CoA 



No discussion of coenzymes would be complete without 

 reference to the chemical synthesis of these substances. Early 

 workers, notably Levene, Kuhn, Karrer, and Folkers, had ac- 

 complished the total synthesis of several coenzymes of the 

 mononucleotide class. But no member of the dinucleotide 

 group had been prepared, owing to the formidable obstacles in 

 the synthesis of unsymmetrically substituted pyrophosphates. 

 About 10 years ago A. R. Todd (40) and his associates at Cam- 



505 



