COENZYMES DERIVED FROM B VITAMINS 133 



mols are liberated from coenzyme II. The results of degradation of the 

 coenzymes have excluded all but one possible structure for cozymase, 17 

 but have not given sufficient data to establish the exact formula for 

 coenzyme II. They are both inner salts of ribose dinucleotides in which 

 the organic bases are nicotinamide and adenine. The problems encoun- 

 tered in attempting to synthesize such dinucleotides have not yet been 

 solved, and it has been impossible to verify the proposed structures by 

 synthesis. 



It was originally postulated that the third phosphate group of coenzyme 

 II formed a linear pyrophosphate "chain" with the two other phosphate 

 residues. 18 However, it is now believed that the additional phosphate is 

 attached in some position as a "side chain," presumably by forming an 

 ester with one of the hydroxyl groups of the adenosine component. This 

 structure would account for the ease with which the triphospho- coenzyme 

 can be degraded to cozymase, since the reaction would then not entail a 

 cleavage and resynthesis of the dinucleotide bond during the conversion. 



A number of trivial synonyms have been coined for the two coenzymes; 

 for most of them there are obvious objections. The thiamine coenzyme 

 is also a cof actor essential for zymase activity; hence, it too is a "co- 

 zymase" and a "coferment." "Coreductase" and "codehydrogenase" can 

 logically be applied equally well to coenzymes which contain no nicotin- 

 amide. Both coenzymes of nicotinamide plus several degradation products 

 can serve as "Factor V," the growth factor required by Hemophilus 

 influenzae. Designation of compounds by numerals or by the names of 

 investigators can be very confusing even to scientists well acquainted 

 with the historical aspects of biochemistry. Names based upon chemical 

 structure are the desirable choice. For this reason, diphosphopyridine 

 nucleotide (DPN) will be used in preference to cozymase, coenzyme I, 

 codehydrogenase I, coferment of alcoholic fermentation, Harden's cofer- 

 ment, coreductase, or Factor V; triphosphoptjridine nucleotide (TPN) 

 will be used to designate the compound which was originally called coen- 

 zyme II (codehydrogenase II) or Warburg's coferment. 



The formula and names given above represent the oxidized states of 

 the coenzymes. The reducd forms are referred to as the dihydro com- 

 pounds. In the oxidized state, the nucleus of the nicotinamide exists as 

 a quaternary pyridinium ion which forms an inner salt with one of the 

 ionizable acid groups in the pyrophosphate bridge between the two 

 nucleosides. Upon reduction, the heterocyclic nitrogen atom is converted 

 to the weakly basic tertiary amine; hence the reduced disphosphopyridine 

 nucleotide behaves as a dibasic acid. The reduction of either coenzyme is 

 thus always accompanied by an increase in the number of titratable 

 hydrogen ions. Which one of the two ortho positions (2 or 6) is hydro- 



