DIGESTION, ETC. OF FAT-SOLUBLE VITAMINS 33 L 



Black and co-workers 547,548 were the first to demonstrate that sulfa- 

 guanidine reduces the growth rate of young rats, and that this effect is 

 accompanied by a hypoprothrombinemia 548 ; this effect could be counter- 

 acted by the administration of vitamin K. Succinyl sulfathiazole (sulfa- 

 suxidine) has also been found to reduce the growth rate in the rat and to 

 lower the prothrombin level. The effects of this sulfonamide were like- 

 wise found to be counteracted by vitamin K, as well as by a liver extract. 548 

 Kornberg, Daft, and Sebrell 549 reported shortly thereafter that sulfa- 

 pyrazine, sulfadiazine, and sulfathiazole were more effective in producing 

 vitamin K deficiency than was sulfaguanidine, succinyl sulfathiazole, or 

 sulfanilamide. These workers also proved that neither absorption, 

 utilization, nor alteration in vitamin K requirement could be considered 

 significant elements in the production of vitamin K deficiency by the 

 sulfonamides. 



It is known that coliform organisms produce vitamin K in vitro bbu 

 and that sulfaguanidine and succinyl sulfathiazole reduce the coliform 

 count in the feces of rats. 551 On the other hand, p-aminobenzoic acid, 

 which Black et a/. 548 showed was effective in counteracting vitamin K 

 deficiency produced by feeding sulfaguanidine is known to antagonize 

 sulfonamide bacteriostasis. 



The action of sulfaguanidine in producing vitamin K deficiency is ex- 

 plained by Black and associates 548 as due in part to the effect of this drug 

 in inhibiting the synthesis of vitamin K by the intestinal flora. This 

 theory is substantiated by Kornberg, Draft, and Sebrell, 552 who demon- 

 strated that the cecal contents and the collected feces of rats with vitamin 

 K deficiency produced by sulfonamides contained only slight vitamin K 

 activity or none at all. On the other hand, these products from control 

 rats had a much greater vitamin K activity. The work of Day et al., bbS 

 who found that cecectomy increased the incidence of vitamin K deficiency 

 in rats fed succinyl sulfathiazole, also supports the above hypothesis. 



547 S. Black. J. M. McKibbin, and U. A. Elvehjem, Proc. Soc. Exptl Biol. Med., 47, 

 308-310 (1941). 



548 S. Black, R. S. Overman, C. A. Elvehjem, and K. P. Link, J. Biol. Chem., 145, 137- 

 143(1942). 



549 A. Kornberg, F. S. Daft, and W. H. Sebrell, Pub. Health Reports, U. S. Pub. Health 

 Service, 59, 832-844 (1944). 



560 S. Orla-Jensen, A. D. Orla-Jensen, H. Dam, and J. Glavind, Zentr. Bakteriol., Abt. 2, 

 104, 202-204 (1941); Chem. Zentr., 113, 1155 (1942). 



561 O. K. Gant, B. Ransone, E. McCov, and C. A. Elvehjem, Proc. Soc. Exptl. Biol. 

 Med., 52, 276-279(1943). 



552 A. Kornberg, F. S. Daft, and W. H. Sebrell, J. Biol. Chem., 155, 193-200 (1944). 



553 H. G. Dav, K. G. Wakim, M. M. Krider, and E. E. O'Banion, J. Nutrition, 26, 

 585-(i00(1943). 



