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.
