A comparison between vitamin K-dependent carboxylase from normal and warfarin-treated cows

Detergent-solubilized microsomal preparations that catalyse the vitamin K-dependent γ-carboxylation of glutamic acid residues in peptide and protein substrates, have been obtained from the livers of normal and warfarin-treated cows. The preparations from warfarin-treated animals contained more endogenous substrate than those from normal cows, but otherwise the two preparations were indistinguishable. The enzymes vitamin K reductase and γ-glutamyl carboxylase, may function independently of each other in this system. They are, nevertheless, intimately linked in some way, so that the reduced vitamin K that is produced by the former enzyme can be used immediately by the latter.     

Warfarin-induced accumulation of vitamin K-dependent proteins comparison between hepatic and non-hepatic tissues

At high concentrations (7.5 mg/kg body weight), coumarin derivatives inhibit the vitamin K-dependent carboxylation reaction in hepatic as well as in non-hepatic tissues. Therapeutically this anti-vitamin K drug is frequently used in 100-fold lower dosages. Under these conditons the production of the vitamin K-dependent clotting factors in the liver is only partially inhibited. Using the rat as an experimental animal, we could demonstrate, that during a dayly intake of these low amounts of warfarin, endogenous substrates for vitamin K-dependent carboxylase accumulate in the lung, spleen and testis in a similar way as they do in liver. Therefore it seems that in vivo the carboxylating enzyme systems in all these tissues are inhibited. It seems plausible, that this effect of warfarin is not restricted to rats, but that it will also occur in patients under anticoagulant therapy.     

The importance of plankton to Cassin's auklets during breeding

The breeding chronology, food habits, growth and reproductivesuccess of Cassin's Auklets, Ptychoramphus aleuticus, were investigatedon Triangle Island, British Columbia. The breeding of Cassin'sAuklets coincides with the plankton bloom in the eastern NorthPacific. Cassin's Auklets in British Columbia feed their youngmostly large copepods, Calanus cristatus, and euphausiids, chieflyThysanoessa spinifera, but fish was an important food item inone summer. Chicks which hatched early, grew and survived betterthan late-hatched chicks and this may relate to food availability.Adults and chicks on Triangle Island were heavier than thoseon South Farallon Island, California. The heavier weight andgreater numbers of Cassin's Auklets in British Columbia as comparedwith regions to the south may relate to Calanus cristatus availabilityand abundance in northern areas.     

Extraction of osteocalcin from fossil bones and teeth

Osteocalcin (also called 'bone Gla-protein') was detected in fossil bovid bones ranging from 12,000 years to 13 million years old and in rodent teeth 30 million years old. Both the antigenic activity and the protein-bound Gla-residues have remained intact. The protein is indistinguishable from recent bovine osteocalcin when analyzed by HPLC using ion exchange and size exclusion columns. If sufficient amounts can be extracted and an adequate purification procedure is established, this would be the first time that amino acid sequences in a protein from fossil bones may be determined. Such sequence data could offer a new approach to the phylogenetic study of extinct taxa.     

The binding of Gla-containing proteins to phospholipids

It is demonstrated here that osteocalcin, the Gla-containing protein from bone, is unable to interfere with the binding of the blood coagulation factors to phospholipid vesicles. Therefore, it seems that besides the Gla residues other structural features of the coagulation factors are required for their effective binding to phospholipid surfaces.