BIOTIN 



4. E. J.-H. Chu and R. J. Williams, /. Amer. Chem. Soc, 1944, 66, 



1678. 



5. D. Burk and R. J. Winzler, Science, 1943, 97, 57. 



6. M. N. Coryell, M. E. Harris, S. Miller, H. H. Williams and I. G. 



Macy, Amer. J. Dis. Child., 1945, 70, 150. 



12. INTESTINAL SYNTHESIS OF BIOTIN 



The synthesis of biotin by the intestinal flora of experimental 

 animals was first demonstrated by the administration of sulphon- 

 amides, which inhibited the growth of the bacteria that produced 

 biotin. Daft et al.^ for example, showed that rats given snlphaguani- 

 dine and sulphasuxidine developed dermatitis, necrosis of the heart 

 muscle, haemorrhage into various organs and the subcutaneous tissues, 

 and liver damage. The symptoms were prevented by administration 

 of crystalline biotin. Similar observations were made by G. J. 

 Martin,2 by E. Nielsen and C. A. Elvehjem,^ by Neumann et al.,^ by 

 G. A. Emerson and E. Wurtz,^ and by A. D. Welch and L. D. Wright. « 

 The symptoms of biotin deficiency in rats maintained on a diet con- 

 taining 1 % of succinyl sulphathiazole were not prevented by the 

 addition of _/)-aminobenzoic acid to the diet.* Only a small amount 

 of biotin was synthesised by rats on a riboflavine-deficient diet '^ and 

 by mice on a synthetic diet.^ The amount of biotin and folic acid 

 stored in the liver was less in rats maintained on a purified diet 

 adequate in the vitamin B complex than in rats fed the stock diet,^ 

 and was further decreased when succinylsulphathiazole was added to 

 the diet. The inference to be drawn from this observation, namely 

 that biotin and folic acid are synthesised by the intestinal flora and 

 then somehow utilised by the animals is supported by the results 

 obtained by Barki et al.,^^ who found that rats maintained on a 

 purified diet under conditions that prevented coprophagy grew better 

 when biotin and folic acid were added to the diet, whereas these 

 supplements made little difference to the growth of rats kept in 

 ordinary screen-bottom cages. The biotin and folic acid contents of 

 the liver were also reduced, and the results suggest, therefore, that 

 rats may obtain part of their biotin and folic acid requirements by 

 ingesting their faeces. Direct absorption from the gut must take 

 place to some extent, however, as the amounts of biotin and folic acid 

 in the liver were still further depressed when succinylsulphathiazole 

 was added to the diet. As already mentioned (page 428), pantothenic 

 acid-deficiency due to the addition of succinyl sulphathiazole to the 

 diet was corrected by administration of biotin and folic acid concen- 

 trates,io the utilisation of pantothenic acid obviously being dependent 



434 



