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B A Soute

Publications and source records attributed to B A Soute.

At least 55 records · Page 3Linked to original sources
PubMed1983

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 conditions 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 daily 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.

Animals↗
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

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↗
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↗