Vitamin K and biosynthesis of protein and prothrombin.

The role of vitamin K in the synthesis of prothrombin has been examined with the following results. 1. Vitamin K deficiency has no effect on general protein synthesis as studied by amino acid incorporation into protein in vivo and in vitro and by tryptophan pyrrolase production following tryptophan feeding. 2. Prothrombin activity was found in normal rat liver microsomes with increased release following ultrasonic treatment, but could not be found in microsomes from the livers of vitamin K-deficient rats or dicumarol-treated rats. Administration of suboptimal levels of vitamin K to vitamin K-deficient rats resulted in detectable microsomal prothrombin in 2 hours and essentially normal values within 3 hours. 3. Adequate vitamin KI, given by injection, completely restored the blood prothrombin levels of vitamin K-deficient rats in 1 hour, and of dicumarolor warfarin-treated rats in 5 to 7 hours depending on the amounts of warfarin and vitamin K1 given. 4. Following administration of actinomycin D or ethionine to vitamin K-deficient rats, treatment with vitamin K1 markedly stimulated prothrombin production, indicating that the site of action of vitamin K is beyond the level of transcription of DNA to prothrombin messenger RNA. 5. Treatment with vitamin K1, following administration to vitamin K-deficient rats of cycloheximide at a level just sufficient to block synthesis of prothrombin for 6 to 8 hours,