SYNTHESIS IX THE (iASTKOl.XTESTlXAL TUACT 759 



the prothrombin time is increased in man after the admmistration of 

 petroleum oil. It is believed that the mineral oil prevents the absorption 

 of the endogenous vitamin K which is synthesized in the intestine, and also 

 of that of exogenous origiii. Alnwiuist'** reviewed the subject of bile in rela- 

 tion to the absorption of vitamin K, m his excellent treatise on this vitamin. 



4. The Synthesis of Vitamin K in the Gastrointestinal Tract 



It has already been mentioned that most bacteria are capable of syn- 

 thesizing vitamin K w^hen grown on a \'itamin K-free medium. Many of 

 the bacteria which ]:»elong in this category are normal hihabitants of the 

 gastrointestinal tract. When these bacteria are prevented from function- 

 ing in their normal manner, and when vitamin K is also withheld from the 

 diet, symptoms of vitamin K deficiency develop very rapidly, in experimen- 

 tal animals as well as in man. 



The sulfa drugs exert a powerful action in the intestine, where they 

 prevent normal bacterial growth. Black et al}^"^^ were the first to demon- 

 strate that sulfaguanidine decreased the rate of growth in rats, and resulted 

 in hypoprothrombinemia. These effects could l)e prevented when vitamin 

 K was administered. Kornberg et al?^ later reported that sulfapyrazhie, 

 sulfadiazine, and sulfathiazole were more effective in producing a defi- 

 ciency of vitamin K than were sulfaguanidine, succinyl sulfathiazole, or sul- 

 fanilamide. The coliform organisms are known to produce vitamin K 

 when incubated in vitro?"^ These are the organisms which appear in reduced 

 amounts in the feces of rats after treatment with sulfaguanidine or succinyl 

 sulfathiazole.^^ Thus, the action of sulfaguanidine in producing vitamin K 

 deficiency is explained by its inhibiting effect upon the synthesis of vitamin 

 K by the intestinal flora.'^^ Support for this theory is given by the results 

 of Kornberg and co-workers,^^ who showed that the cecal contents and the 

 collected feces of rats treated with sulfonamides possessed only a slight 

 \'itami]i K activity. According to Day et al.,^'' cecectomy increases the 

 deficiency of vitamin K in rats fed succinyl sulfathiazole. 



In the case of newborn babies, a vitamin K deficiency sometimes occurs 



^5 S. Black, J. M. McKibbin, and C. A. Elvehjem, Proc. Soc. Expll. Biol. Med., 47, 

 308^310(1941). 



^« A. Kornberg, F. S. Daft, and W. H. Sebroll, Pub. Health Reports, U. S. Pub. Health 

 Serrice, .59, 832-844 ( 1<»44). 



" S. Orla-Jonsen, A. 1). Orla-Jensen, H. Dam, and J. Glaviiid, Zenlr. BacterioL, Abl. 

 2, 104, 202-204 (1941): Chem. Zentr., 113, 1155 (1942). 



■'s O. K. Gant, B. Ransone, E. McCoy, and C. A. Elvehjem, Proc. Soc. Exptl. Biol. 

 .Uer/., .5^, 276-279 (1943). 



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



