116 THE BIOCHEMISTRY OF B VITAMINS 



vitamin component of the coenzyme.* In vitro, pyridoxal can participate 

 in transamination reactions with amino acids without being phos- 

 phorylated; although the mechanism by which thiamine performs its 

 catalytic function is not understood, there is no reason to expect that the 

 phosphate part of the coenzyme molecule is altered during decarboxyla- 

 tions. It seems in most instances that the chemical changes catalyzed by 

 a vitamin-containing enzyme are directly mediated by the vitamin com- 

 ponent of the coenzyme, but the vitamin itself does not readily associate 

 itself with the apoenzyme; hence, the function of the nonvitamin portion 

 must in some way be concerned with the mechanism by which the co- 

 enzyme associates itself with the apoenzyme. Until some better explana- 

 tion can be offered, it can be postulated that an important reason for the 

 conversion of a vitamin to its coenzyme is to enable the molecule to con- 

 tain the chemical groups which are essential for the formation of the 

 coenzyme-protein bond. 



Formation of Holoenzymes. One of the most intriguing properties 

 exhibited by many proteins is their remarkable ability for combining with 

 specific compounds of smaller molecular weight. It is impossible to give 

 any adequate explanation of this phenomenon in terms of the classical 

 concepts of chemical bonds. The inadequacy of our knowledge is fre- 

 quently hidden behind the veil of such ambiguous terms as "protein com- 

 plexes" and "enzyme-substrate union." 



The binding of an apoenzyme with its coenzyme should be considered 

 as a special case of the general phenomenon of combination between 

 enzymes and substrates. In fact, in a number of reactions the participat- 

 ing coenzyme can more properly be termed a substrate than a catalyst. 

 These are the reactions in which coenzymes are chemically altered during 

 the course of the reaction and must be reconverted to their original form 

 by a second reaction entirely separate from the first (p. 137). In such 

 cases the coenzyme is in a strict sense the catalyst for a process, but 

 not for the individual reactions. 



Any attempt to develop a general explanation for the association 

 between coenzymes and proteins is further complicated by the extreme 

 variation in the stability of the union. Some systems exist in which the 

 dissociated apoenzyme and coenzyme are present in greater concentrations 

 than the holoenzyme; at the other extreme are the enzymes whose pros- 

 thetic groups are so firmly bound that hydrolysis of the protein is neces- 

 sary to release the vitamin component. Also, a particular coenzyme does 



* In the case of nicotinic acid, the conversion of the tertiary amine (the vitamin) 

 to the quaternary ammonium base (the coenzyme) is probably essential for estab- 

 lishing the redox potential appropriate for the reactions catalyzed by the nicotinic 

 acid-enzyme systems. 



