Warfarin and the biochemistry of the vitamin K dependent proteins.
We have reviewed the biochemistry of the normal and warfarinized vitamin K-dependent coagulation proteins, both individually and as members of their respective macromolecular enzyme complexes. Much has been learned in the past 10-15 years about the molecular mechanisms of coagulation. However, we have only scratched the surface and are beset by a number of interesting challenges. Clearly, we must begin to dissect the other vitamin K-dependent macromolecular enzyme complexes as has been done for prothrombinase. Prothrombin differs in fundamental ways from the other vitamin K-dependent proteins and we can anticipate significant differences as well as similarities in the other complexes. The presence of potentially functional domains in the non-catalytic portions of the vitamin K-dependent proteins and their similarities within this family of proteins should prove a fruitful area of future research. Finally, the evaluation of warfarinized vitamin K-dependent proteins, both in fundamental studies with purified systems and using uniquely engineered immunoassays, should shed light on basic molecular mechanisms and modes of monitoring warfarin therapy.
Bovill
E G
EG
University of Vermont, Department of Biochemistry, Burlington 05405.
Mann
K G
KG
D015055:1-Carboxyglutamic Acid / Q000502:physiology*; D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000502:physiology*; D006801:Humans; D005810:Multigene Family; D011506:Proteins / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology; D014812:Vitamin K / Q000502:physiology*; D014859:Warfarin / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D011506:Proteins; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; D014859:Warfarin; D012697:Serine Endopeptidases