title: Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats.
abstract: 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 gamma-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 gamma-glutamylcarboxylase the apparent KM 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.
authors.affiliation: Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: Soute
authors.forename: M M
authors.initials: MM
authors.lastname: Ulrich
authors.forename: A D
authors.initials: AD
authors.lastname: Watson
authors.forename: J E
authors.initials: JE
authors.lastname: Maddison
authors.forename: R H
authors.initials: RH
authors.lastname: Ebberink
authors.forename: C
authors.initials: C
authors.lastname: Vermeer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D019735:Carbon-Carbon Ligases; D002371:Cat Diseases / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D002415:Cats; D005170:Factor X / Q000378:metabolism; D007700:Kinetics; D008025:Ligases / Q000172:deficiency*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011516:Prothrombin / Q000378:metabolism; D013379:Substrate Specificity; D014812:Vitamin K / Q000627:therapeutic use
chemical_list: D010455:Peptides; D014812:Vitamin K; D011516:Prothrombin; D005170:Factor X; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase