COENZYMES DERIVED FROM B VITAMINS 139 



An interesting phenomenon observed in yeast is one in which the 

 presence of a substrate appears to protect a coenzyme from destruction. 

 The crude apozymase preparations rapidly inactivate diphosphopyridine 

 nucleotide when the latter is added alone, 48 but if hexose diphosphate is 

 added simultaneously the destruction does not take place. Likewise, if 

 the yeast fermentation is inhibited by the presence of the fluoride ion a 

 rapid decrease in coenzyme content results. Apparently, active fermenta- 

 tion is necessary to produce the conditions required either for decreasing 

 the rate of hydrolysis of the coenzyme or for increasing the rate of its 

 resynthesis from its hydrolytic products. A demonstration of coenzyme 

 synthesis by these apoenzyme preparations, however, has not as yet beei. 

 achieved. 



Reactions Catalyzed by Nicotinic Acid-containing Coenzymes. Al- 

 though the reduction of the nicotinic acid coenzymes is often pictured as 

 the simple addition of two hydrogen atoms to one of the — N=C< bonds 

 of the pyridine nucleus, the reduction of the coenzyme is probably not 

 so direct. There is evidence that the reduction is a stepwise procedure 

 in which the intermediate formation of a stabilized semiquinoid radical 

 (monohydronucleotides) allows the addition to the coenzyme of a single 

 hydrogen atom at a time, 49 and facilitates the establishment of an equilib- 

 rium between the oxidized and reduced states. 13 



A wide degree of variation has been noted in the specificity of various 

 nicotinic acid dehydrogenases in their requirements for the two coen- 

 zymes. 50 In most of the reactions that have been investigated there is a 

 distinct preference, if not an absolute requirement, for one or the other 

 of the two compounds. One enzyme (glutamic acid dehydrogenase from 

 animal tissues), however, can use either the di- or triphospho nucleotide 

 equally well. 



Approximately forty different enzyme reactions have been reported to 

 be catalyzed by one or the other of these coenzymes. Although many of 

 these reactions are probably of limited importance in the normal function- 

 ing of cells, a number of indispensable reactions taking place during basic 

 metabolic processes are found in the list. 



The redox potentials for most of the important systems with which 

 pyridine coenzymes are coupled fall in the same range as those of the 

 coenzymes themselves. Consequently, the direction in which these reac- 

 tions proceed can be reversed (1) when changes in metabolism alter the 

 concentration ratio of the metabolite-pair within the cell or (2) when the 

 coenzyme-reduced coenzyme ratio changes because of variations in the 

 intracellular redox potential brought about by other processes taking 

 place. For example, in many instances the direction in which the lactic 

 acid-pyruvic acid conversion proceeds is constantly alternating because 



