Haematologia 18. (1985)
1985 / 2. szám - Vermeer, C. - de Boer-Van Den Berg, Marian: Vitamin K-Dependent Carboxylase
Haematologia 18 (2), pp. 71—97 (1985) Vitamin K-Dependent Carboxylase C. Vermehr, Marian A. G. De Boer-Van Den Berg Department of Biochemistry, University of Limburg, P. O. Box 616, 6200 MD Maastricht, The Netherlands (Received 29 March 1984; accepted 28 April 1984) Vitamin K-dependent carboxylase is found in the liver, where it is involved in the synthesis of four blood coagulation factors and protein C. The hepatic enzyme has partly been purified and several mechanisms have been postulated for the vitamin K-dependent carboxylation reaction. Recently the enzyme has also been detected in other tissues including the lung, kidney, spleen, testis, bone and arterial vessel wall. The proteins produced by these non-hepatic carboxylases are now being characterized, but in most cases their function is still unknown. This paper is meant to review our present knowledge in this field. Keywords: Blood coagulation, y-carboxyglutamic acid, carboxylase, coumarin, vitamin K, warfarin. Introduction Vitamin K is involved in a post-translational modification of proteins and recently several authors have reviewed its role in the formation of the blood clotting factors II (prothrombin), VII, IX and X [1 —4]. The vitamin K-dependent step in protein biosynthesis is the carboxylation of a number of discrete glutamic acid (Glu) residues into y-carboxyglutamic acid (Gla) [5, 6]. This reaction can be inhibited in vivo by the administration of vitamin K-antagonists such as warfarin, phenprocoumon and dicoumarol [7, 8], which leads to the production of non-carboxylated and hence inactive coagulation factors [9]. The three drugs mentioned above are therefore currently used as anticoagulants in rodenticides (rat poison) and in medicine for the control of thrombogenic episodes [10, 11]. Soon after the identification of Gla in blood coagulation factors, other proteins were reported to contain this abnormal amino acid [12—15], and every year a number of proteins is added to those which are called the “Gla-containing” or “vitamin K-dependent” proteins. In this paper we intend to summarize our present knowledge in this field and hope to make it clear that vitamin K- dependent carboxylation is a process which is not restricted to four blood coagulation factors, but that it is a normal modification undergone by numerous other proteins. Haematologia 18, 1985