340 THE BIOCHEMISTRY OF B VITAMINS 



an amino acid {e.g., glutamic acid) may not be as readily released as 

 vitamins not normally so linked in the functional form. 



A brief consideration of the structures of the B vitamins shows that a 

 diversity of active groups is present which may participate in binding to 

 proteins. Carboxylic acid groups are present in five of the B vitamins, 

 hydroxyl groups in six, aliphatic or aromatic primary amino groups in 

 four, and phenolic groups in three, with a scattering of other active struc- 

 tural groupings. Generally phenolic groups and aromatic amino groups 

 remain intact in metabolism so as to function in redox reactions; and 

 hydroxyl groups are frequently phosphorylated in functional forms. It 

 would, therefore, seem most likely that the B vitamins are generally 

 bound via their acid or aliphatic amino groups or via the acid groups of 

 their phosphates to suitable active groups in proteins, and that the 

 amido and salt linkages so formed should be quite readily hydrolyzed 

 by pH extremes or certain phosphatases and digestive enzymes. Thus 

 thiamine, riboflavin, choline, and inositol are the B vitamins which have 

 well known and widely occurring phosphates, but few other good groups 

 for protein binding, and so may logically be bound via phosphate mole- 

 cules to protein ; whereas nicotinic acid, pantothenic acid, p-aminobenzoic 

 acid, biotin, and folic acid do not have widely distributed (or well 

 known) phosphates, but do have carboxylic acid groups capable of combin- 

 ing with free protein amino groupings. Nicotinamide may possibly be 

 bound through its amide grouping ; indeed either it or nicotinic acid might 

 be produced upon liberation, depending upon the course of the action. 

 The B 6 vitamins most logically would be bound via their 5-hydroxy- 

 methyl group (phosphorylated?) since other active groupings are 

 involved in the vitamin function and must necessarily remain intact. 

 Such reasoning supposes that each vitamin contains separate groupings 

 for performing its primary function and for attaching it to its protein 

 enzyme — an hypothesis which fits well the existing information on this 

 subject. In vitro studies with pure enzyme preparations should do much 

 to elucidate the nature of the binding involved in each case, and the 

 enzymes capable of vitamin liberation. The fact that the avidin-biotin 

 complex is not broken by the intestinal processing indicates that the 

 nature of the binding may not be deduced with complete accuracy on 

 the basis of structural considerations alone, although the — CO — NH — 

 grouping common to both biotin and protein linkages may be suggestive 

 of secondary binding effects. 



Individual differences in digestive ability, whether within physiological 

 or pathological limits, are doubtless among the important factors which 

 influence the broad individual differences in B vitamin requirements. 

 This fact is extremely evident in the case of the folic acid conjugases, 



