112 THE BIOCHEMISTRY OF B VITAMINS 



High levels of a vitamin might, however, exert an effect which is just 

 the opposite, i.e., the high concentration might increase the apparent 

 activity of a coenzyme by slowing down its destruction. Thus, nicotin- 

 amide has been observed to inhibit the enzymatic destruction of its 

 coenzyme in minced tissues. 9 The investigators making this observation 

 believed that the extent of inactivation of the coenzyme was decreased 

 by the increased concentration of one of the products (nicotinamide) of 

 the inactivating reaction. Thiamine has been shown to be a specific in- 

 hibitor for certain enzymes which catalyze the hydrolytic destruction of 

 its coenzyme (p. 156). 



Biosynthesis of the Coenzymes. In vivo, the coenzymes are formed by 

 enzymatic reactions in which the vitamins themselves serve as substrates. 

 The coenzymes vary in their chemical complexity, and presumably some 

 vitamin-to-coenzyme transformations require more than one reaction. 

 The simplest coenzymes are those in which the vitamin is converted to a 

 phosphoric acid ester. Thiamine, riboflavin, and pyridoxal fall in this 

 group. Riboflavin, nicotinic acid, pantothenic acid, and perhaps biotin 

 form more elaborate molecules which contain the nucleotide, adenylic 

 acid, as a component. The simpler coenzymes have all been synthesized 

 chemically by direct phosphorylation of the vitamin. Every attempt to 

 synthesize adenylic acid-containing coenzymes by chemical means has 

 been unsuccessful. 



It is interesting to consider the possible existence of unrecognized vita- 

 mins required for the reactions converting B vitamins to their coenzymes. 

 Thus, if some cofactor of a system essential for a reaction which produces 

 one of the recognized coenzymes could not be synthesized by an animal, 

 this cofactor could be an essential dietary factor or vitamin. However, 

 the amount of a catalyst needed to catalyze the formation of a catalyst 

 would be extremely small; hence the nutritional requirements for such 

 factors may be extremely minute, and demonstrating their existence would 

 be difficult. Such a coenzymatic role has been suggested for vitamin Bi 2 

 (in the biosynthesis of the coenzymes of p-aminobenzoic and folic acids, 

 p. 203). This would account for the clinical activity of vitamin B 12 in 

 one-thousandth the amounts required for other vitamins. 



It may often happen that appreciable amounts of a vitamin may be 

 supplied to an organism in a chemical form which cannot be directly 

 utilized as the substrate for the synthesis of the necessary coenzyme. 

 Other reactions must then precede the final transformation. If an or- 

 ganism is deficient or lacking in enzymes capable of catalyzing the needed 

 change, then that form of the vitamin will show less activity or be totally 

 inactive. It appears, for example, that pyridoxine must be oxidized to the 

 aldehyde before it can be converted into a coenzyme; hence the vitamin 



