Congenital Deficiency of All Vitamin K-Dependent Blood Coagulation Factors Due to a Defective Vitamin K-Dependent Carboxylase in Devon Rex Cats

Summary

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K₁ resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective γ-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to γ-glutamylcarboxylase the apparent K _M for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.

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