456 THE BIOCHEMISTRY OF B VITAMINS 



Biological Action of Analogues of B Vitamins. Although some vitamin 

 analogues are converted in vivo to the corresponding vitamin, such is not 

 always the case. An analogue may combine with the enzyme involved in 

 the conversion of the vitamin to its coenzyme. The enzyme-analogue 

 complex either may be nonfunctional, resulting in competitive inhibition, 

 or it may function in a manner identical with that of the vitamin. In the 

 latter case an analogue of the normal coenzyme will be formed. If the 

 modified coenzyme cannot be utilized by the proper apoenzyme, the result 

 is still a competitive inhibition of coenzyme formation. However, if 

 modified coenzymes resulting from the analogue can be utilized by the 

 apoenzymes, the analogue is capable of replacing the vitamin in the 

 biological system. Some modified coenzymes apparently can be utilized 

 by only some of the apoenzymes which normally combine with the natu- 

 ral coenzyme. In such cases, supplements of the products of the enzyme 

 systems which cannot utilize the modified form of the coenzyme are 

 essential for the vitamin-like activity of an analogue which can replace 

 all other coenzyme functions of the vitamin. Similar considerations apply 

 in case more than one coenzyme is derived from the vitamin. Only one 

 of the coenzymes might be replaced by a similar product derived biologi- 

 cally from the analogue. 



The analogue of a vitamin may prevent the utilization of a vitamin at 

 any stage in the biosynthesis and functioning of the coenzyme; however, 

 if two successive stages in the utilization of a vitamin are inhibited by 

 a single analogue, the vitamin would be capable of preventing the inhibi- 

 tion only over a small range of concentrations. 



Structural Modifications Producing Vitamin Analogues with Biological 

 Activity. In order for a compound to inhibit the functioning of or replace 

 a natural metabolite in a biological system, the substance must possess 

 the ability to combine with a particular enzyme utilizing the metabolite. 

 The ability to combine with a particular enzyme at the specific point at 

 which the metabolite associates with the enzyme is determined not only 

 by the presence of certain functional groups which are instrumental in 

 effecting such a combination, but also upon the shape, size and configura- 

 tion of the molecule. Consequently, most of the compounds which either 

 replace or inhibit a vitamin in its functioning in a biological system are 

 related structurally to the vitamin. 



The types of modifications which produce compounds with such biologi- 

 cal activities include replacement of groups occurring in the metabolite 

 as follows: -S- by -CH = CH- _CH 2 -CH 2 - or -S0 2 -; benzene 

 nucleus by aromatic heterocyclic nuclei such as thiophene, pyrimidine, 

 pyridine, etc. nuclei ; -COOH by -S0 2 -NH 2 , -S0 3 H, -S0 2 -R, -SO-R, 

 -P0 3 H 2 , -P0 2 H, -As0 3 H 2 , -CH 2 OH, -COR, etc.; -CH 3 by -CI, 



