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Biomedical subjects

C Vermeer

Publications and source records attributed to C Vermeer.

At least 127 records · Page 7Linked to original sources
PubMed1983

Stimulation of the vitamin K-dependent carboxylase from bovine liver.

Vitamin K-dependent carboxylase from bovine liver is stimulated not only by reducing agents and bivalent metal ions (especially Mn2+), but also by several organic solvents (dimethyl sulphoxide, ketones and acetonitrile). The organic solvents stimulated both the carboxylation of glutamic acid residues and the formation of vitamin K epoxide. This stimulation by organic solvents was independent of the physical state of the phospholipid; it was highest at low temperatures and could only be demonstrated with vitamin K1 and not with 3-DTT-MK-O (the thioether adduct of menadione and dithiothreitol) or t-butyl hydroperoxide, which normally can substitute for vitamin K. We suggest that organic solvents exert their effect by changing the mobility of the isoprenoid side chain of vitamin K1 within the carboxylase complex.

Animals↗
PubMed1982

Vitamin K-dependent carboxylases from non-hepatic tissues.

The presence of vitamin K-dependent carboxylase was investigated in the microsomal fraction of 20 different types of bovine tissue. Except for muscle, veins, lymphocytes and bone membrane, carboxylase was found in all these preparations, albeit in varying amounts. No differences could be detected between these carboxylating systems with respect to their affinity for vitamin K and warfarin. Most of the endogenous substrates had some affinity towards antiprothrombin or antifactor X.

Animals↗
PubMed1982

Vitamin K-dependent carboxylase in horse liver, spleen and kidney.

The presence of vitamin K-dependent carboxylase is demonstrated in the microsomal fraction of horse liver, spleen and kidney. The carboxylating enzyme systems in the spleen and in the kidney are susceptible to warfarin in a similar way as is carboxylase from the liver. It is concluded, that during the administration of vitamin K-antagonists (anticoagulation therapy) carboxylase in all these tissues is inhibited. Since most probably the majority of the reaction products of spleen and kidney carboxylase are no clotting factors, the inhibition of their production is a side-effect of the anticoagulation therapy. Whether this side-effect is harmful, neutral or even advantageous for the organism in vivo can only be judged, when the function of the various extrahepatic vitamin K-dependent proteins is known.

Animals↗
PubMed1982

Characteristics of vitamin K-dependent carboxylating systems from human liver and placenta.

Bovine liver vitamin K-dependent carboxylase was compared with that obtained from human liver and placenta. Human liver microsomal preparations contained more endogenous substrate than did bovine preparations, but no differences were found between the two types of hepatic enzyme. This observation demonstrates that the bovine liver carboxylating enzyme system is a good model system which will help us to understand vitamin K action in man. Placental carboxylase differed from the liver systems because only vitamin K hydroquinone and not vitamin K quinone could be used as a coenzyme for the carboxylation reaction. Obviously, vitamin K reductase was absent in these preparations.

Animals↗
PubMed1982

Studies on the mechanism of the vitamin K-dependent carboxylation reaction. Carboxylation without the concurrent formation of vitamin K 2,3-epoxide.

In addition to the three known forms of vitamin K (vitamin K quinone, vitamin K hydroquinone, and vitamin K epoxide), a fourth metabolite, hydroxyvitamin K, was found in reaction mixtures containing a vitamin K-dependent carboxylating enzyme system. When sulfite was added to such reaction mixtures, the formation of hydroxyvitamin K was substantially enhanced, whereas no epoxide was formed anymore. The vitamin K-dependent carboxylation was stimulated at these sulfite concentrations. Vitamin K hydroquinone could be replaced by t-butylhydroperoxide and also under these conditions the carboxylation was enhanced by sulfite. In the presence of peroxidase, the carboxylation reaction was blocked, whereas hydroxyvitamin K could still be detected in the reaction mixtures, even in the absence of sulfite. These observations lead us to the hypothesis that the carboxylation of glutamic acid residues is coupled to the heterolytic cleavage of a peroxide bond with the concurrent formation of vitamin epoxide.

Animals↗
PubMed1982

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

Detergent-solubilized microsomal preparations that catalyse the vitamin K-dependent gamma-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 gamma-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.

Animals↗
PubMed1981

Identification of phospholipid as an essential part of bovine vitamin K-dependent carboxylase.

Vitamin K-dependent carboxylase from bovine liver contains phospholipid (primarily phosphatidylcholine), which is essential for its in vitro activity. Sepharose-bound carboxylase can be depleted of phospholipids, either by washing the enzyme with detergents or by phospholipase treatment. The enzyme can be reconstituted by adding mixed micelles of phosphatidylcholine and cholate to the Sepharose-bound proteins.

Animals↗
PubMed1979

Control of anticoagulant therapy with a chromogenic substrate.

Prothrombin is determined with the aid of a recently developed assay, based on the amidolysis of a chromogenic substrate. The assay proved to be reliable when it was compared with more conventional coagulation assays in the control of oral anticoagulant therapy, both in the therapeutic range and in a case of overdosage. As is the case in coagulation tests, heparin therapy remains a disturbing circumstance. The prothrombin concentration was measured (a) in the plasma of 50 long-term anticoagulated patients, and the results were compared with those obtained with a one-stage coagulation assay and with those obtained with Thrombotest determinations, and (b) during vitamin K administration in the plasma of a patient with a severe intoxication of a vitamin K antagonist.

Anilides↗
PubMed1978

In vitro prothrombin synthesis from a purified precursor protein. II. Partial purification of bovine carboxylase.

In this paper, we describe the isolation and partial purification of an enzyme system that converts bovine decarboxyfactor II (PIVKA-II) into prothrombin (factor II). It is shown that the increase in factor II activity occurs in parallel with 14CO2 incorporation into BaSO4 adsorbable proteins. The system is not strictly vitamin K-dependent because it is obtained from the livers of normal healthy cows. By preincubating the enzyme(s) with an excess of warfarin, an absolute vitamin K1-dependence can be obtained. The reaction is inhibited by its own product, factor II.

Animals↗
PubMed1978

The role of blood clotting factor V in the conversion of prothrombin and a decarboxy prothrombin into thrombin.

Purified PIVKA-II exhibits some factor II (prothrombin) activity in the one-stage coagulation assay and this factor II activity does not come from residual amounts of factor II but originates from PIVKA-II itself. It is shown that PIVKA-II is converted by a normal prothrombinase complex (factor Va and factor Xa adsorbed onto a phospholipid interface) more readily than by phospholipids and factor Xa alone. This suggests that binding between PIVKA-II and factor Va is an essential feature in the formation of the enzyme . substrate complex and from this we infer that a direct interaction between factor Va and prothrombin plays a rôle in the prothrombinase . prothrombin complex.

Animals↗