RIBOFLAVIN 671 



6-phosphate was oxidized to phosphogluconic acid by yeast hexosemono- 

 phosphate dehydrogenase. The coenzyme II required for the oxidation 

 was supplied from horse blood, and the yellow enzyme necessary to com- 

 plete the system was provided as the apoenzyme. The activities of the 

 analogues in replacing riboflavin as a coenzyme for the yellow enzyme 

 are shown in Table 38. 



Another coenzyme containing riboflavin was discovered in 1936 by 

 Das 34 as a dialyzable coenzyme of an amino acid oxidase, and was later 

 isolated by Straub 35 and by Warburg and Christian. 30 ' 37 The latter 

 investigators demonstrated that the coenzyme contained a flavin and 

 adenine in the form of a dinucleotide. This coenzyme, which is considered 

 a combination of adenylic acid and riboflavin-5'-phosphate by a pyro- 

 phosphate bond, is more versatile in its action than riboflavin-5'-phos- 

 phate, which cannot replace the dinucleotide for many apoenzymes. 38 

 The dinucleotide can replace riboflavin phosphate in the yellow enzyme, 

 and Lactobacillus casei utilizes either of these coenzymes as efficiently as 

 riboflavin. 



Of the eight stereoisomers corresponding to the structure of riboflavin, 

 seven of these have been synthesized. These include the stereoisomers 

 containing in place of the 9-D,l'-ribityl group of riboflavin the following 

 groups: L,l'-ribityl, 17 D,l'-arabityl, 12 - 17 " 22 L,l'-arabityl, 6 - 18 > 23 " 26 d,1'- 

 lyxityl, 17 D,l'-xylityl, 5 - «• 23 - 27 or 9-L,l'-lyxityl. The 9-L,l'-lyxityl 

 stereoisomer (L-lyxoflavin) has recently been isolated from human heart 

 muscle and synthesized, 39 but no biological tests were reported. Of the 

 other stereoisomers, only the D,l'-xylityl and L,l'-arabityl derivatives 

 are reported to have activity in replacing the vitamin in the nutrition of 

 rats. These two compounds are effective sometimes for only a few weeks 

 with an average growth of the animals of about 30 g. 18 - 27 The standard 

 weight gain for rats of 40 g in 30 days with 8 y per day of riboflavin was 

 never obtained, even with as large amounts as 150 y per day of either 

 of the two stereoisomers. 27 



Only slight alterations of the riboflavin structure can be made if the 

 biological activity is retained. The analogues most effective in replacing 

 the vitamin are those containing modifications of the benzene ring of 

 riboflavin (Table 38). The analogue with an ethyl group in place of the 

 6-methyl group appears to be almost as active as riboflavin for rats, 

 Lactobacillus casei and Bacillus lactis acidi. Modifications involving the 

 elimination of either the 6- or 7-methyl group possess appreciable 

 biological activity of the vitamin; however, at least one of the methyl 

 groups is essential for this activity, since, in contrast to these compounds 

 and the corresponding 6,7-dimethyl derivatives, 9-(D,l-ribityl)isoalloxa- 

 zine 40 and 9-(d or L,l'-arabityl)isoalloxazine 6 - 26> 41 are inactive in 



