672 THE BIOCHEMISTRY OF B VITAMINS 



replacing riboflavin for rats and as a coenzyme in the yellow enzyme. 32 

 Other known modifications of riboflavin involving the benzene ring have 

 only slight stimulatory effects, or are inactive in replacing the vitamin. 

 The 6,7-dimethyl groups of the L-arabityl stereoisomer of riboflavin can 

 be replaced by either a 6,7-trimethylene or 6,7-tetramethylene group 

 without complete loss of the biological activity for rats and the yellow 

 enzyme (Table 38). 7-Ethyl-9(D,r-ribityl)isoalloxazine has a growth- 

 promoting effect for rats, but the response is not constant. 13 Essentially 

 inactive alone, 5,6-benzo-9-(D,r-ribityl)isoalloxazine 13, 30 and 6-ethyl- 

 7-methyl-9-(L,l'-arabityl)isoalloxazine 13, 30 enhance the response of 

 Lactobacillus casei and Bacillus lactis acidi to riboflavin. 30 No growth- 

 promoting activity for rats has been reported for either 5,6-dimethyl-9- 

 (L,l'-arabityl)- or 6,8-dimethyl-9-(D,r-ribityl)isoalloxazine. 42 6,8, Di- 

 methyl-9-(D or L,l'-arabityl(isoalloxazine 43 and 5,7-dimethyl-9-(D or 

 L,r-arabityl)isoalloxazine 43 are inactive for rats and as a coenzyme for 

 the yellow enzyme. 5,6-Benzo-9-(L,r-arabityl)isoalloxazine is inactive 

 for rats. 13 



Replacement of the D-ribityl-group in riboflavin by glycosido-group- 

 ings results in total loss of biological activity. Thus, 6,7-dimethyl-9-(D- 

 or L,l'-arabinosido) and 6,7-dimethyl-9-(D-ribosido)isoalloxazine are 

 inactive in replacing riboflavin in the nutrition of the rat 44 or in function- 

 ing as a coenzyme for the yellow enzyme. 32 



With exception of the D-xylityl and L-arabityl stereoisomers of ribo- 

 flavin, substitution of similar groups for the 9-D,l'-ribityl group in ribo- 

 flavin produces inactive substances. These are exemplified by compounds 

 containing the following substituents in the 9-position: D-l'-desoxy- 

 ribityl, 34 L,l'-rhamnityl, 6 or n-amyl. 24, 27, 45 Similarly, a complete loss 

 of activity is obtained with analogues of 7-methyl-9-(D,r-ribityl)- 

 isoalloxazine in which the ribityl group is replaced by the L,l'-ara- 

 bityl, - 26 D,r-xylityl,'''- 2e D,l'-sorbityl, 6 - 26 D-l'-dulcityl, 5 - c or D,l'-man- 

 nityl 5 - 6 group. 



Substitution of a methyl group in the 3 position of riboflavin results 

 in complete loss of vitamin activity for the rat. 8 The 3,6,7-trimethyl- 

 9-(D,l / -ribityl)isoalloxazine is also inactive in the yellow enzyme test. 

 Since this analogue does not combine with the protein, and since neither 

 it nor the yellow enzyme shows the fluorescence characteristic of ribo- 

 flavin and the free coenzyme, it has been proposed that the 3-position 

 is one point of attachment of coenzyme to the apoenzyme. 46 Because the 

 riboflavin-5'-phosphate combines more readily than the free vitamin 

 with the protein, the phosphate group has been considered as another 

 point of combination with the apoenzyme. 46 



When riboflavin is esterified, the resulting derivatives vary consider- 

 ably in their ability to replace riboflavin for biological systems. Activity 



