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Biomedical subjects

C Vermeer

Publications and source records attributed to C Vermeer.

At least 109 records · Page 6Linked to original sources
PubMed1986

The vitamin K-antagonism of salicylate and warfarin.

When administered in high dosages, salicylate acts as a vitamin K-antagonist: it induces a decrease of the plasma concentration of the Gla-containing coagulation factors and an accumulation of microsomal substrates for vitamin K-dependent carboxylase in the liver and in the lung. In vitro the drugs inhibit the DTT-dependent reductases which mediate the reduction of vitamin K epoxide and vitamin K quinone. NADH-dependent reductase and vitamin K-dependent carboxylase are not inhibited.

Animals↗
PubMed1986

The effect of microgravity on plasma-osteocalcin.

The rapid loss of bone mass is one of the serious problems which have to be solved before long-lasting manned spaceflights may be considered. In this paper we describe investigations in which we have checked whether the bone loss in astronauts as well as in osteoporotic patients may be related to abnormalities in a recently discovered calcium-binding protein, named osteocalcin. It was observed that in all subjects of a limited number of osteoporotic patients, the amount of calcium-binding groups (Gla-residues) in the circulating osteocalcin was substantially reduced. The Gla-content could be normalized, however, by the oral administration of vitamin K (1 mg/day). We also analyzed the Gla-content of plasma-osteocalcin from 4 astronauts before and after the D-1 mission. The amount of Gla-residues was reduced by more than 50% in the post-flight samples. It seems probable, that an increased vitamin K-intake by the astronauts will correct the observed abnormality, but whether this will lead to a decrease of the microgravity-induced bone-loss remains to be seen.

1-Carboxyglutamic Acid↗
PubMed1986

Vitamin K-dependent carboxylase in skin.

Vitamin K-dependent carboxylase is demonstrated in skin microsomes from humans, rats, rabbits, and mice. This enzyme converts a number of distinct protein-bound glutamic acid residues into gamma-carboxyglutamic acid residues, which strongly interact with Ca++ ions. The enzymatic activity (expressed per mg protein) in skin is about 20% of that in liver. Vitamin K-dependent carboxylase is present in both epidermal and dermal tissue. It is demonstrated that warfarin treatment in mice results in an accumulation of noncarboxylated precursor proteins in both dermal and epidermal microsomes. Most probably this effect of warfarin is not restricted to mice, but occurs also in the skin of patients under oral anticoagulant therapy. A possible relation between vitamin K-dependent skin carboxylase and the gamma-carboxyglutamic acid-containing protein in calcified nodules from patients with scleroderma and dermatomyositis is discussed.

Animals↗
PubMed1986

Comparison between hepatic and nonhepatic vitamin K-dependent carboxylase.

Vitamin K-dependent carboxylase is a microsomal enzyme system involved in the carboxylation of protein-bound glutamic acid residues. In mammals, the enzyme is found in many different types of tissue. Hence carboxylated ('Gla-containing') proteins are widely distributed in nature. Neither in vitro nor in vivo differences have been observed with respect to the vitamin K-binding sites of the various carboxylases. Differences between the substrate-binding sites could only be compared after suitable substrates became available. These substrates were prepared from descarboxyprothrombin, osteocalcin and a sperm Gla protein. Substantial differences were detected between the Michaelis constants of various carboxylases for the three substrates mentioned above. It is concluded that vitamin K-dependent carboxylase is a group name for a family of isoenzymes.

Animals↗
PubMed1986

Vitamin K and the urogenital tract.

Solubilized microsomes from bovine liver, kidney and testis were compared with regard to their content of vitamin-K-dependent carboxylase, the presence of endogenous vitamin K as well as that of endogenous carboxylatable precursor proteins. The isolation and purification of these protein substrates was not successful. Using antibodies against various well characterized proteins containing gammacarboxyglutamic acid (Gla), we were able to identify precursors of the blood coagulation factors II, IX and X in liver microsomes. The nonhepatic proteins could not be identified in this way. Gla-containing proteins, however, were isolated from human sperm, urine and renal stones. It was demonstrated that - like osteocalcin - also the urinary Gla protein inhibits the precipitation of various calcium salts from supersaturated solutions. The concentration of the urinary Gla protein (16 mg/l) in human urine is well above the concentration required for the in vitro inhibition of salt precipitation.

Animals↗
PubMed1986

gamma-Glutamyl carboxylase activity in experimental tumor tissues: a biochemical basis for vitamin K dependence of cancer procoagulant.

Rabbit V2 carcinoma tissues have been described to possess a procoagulant activity with specific characteristics; this material has been purified and identified as a cysteine proteinase able to directly activate coagulation factor X. We have shown here that the procoagulant activity of V2 carcinoma extracts is depressed in warfarin-treated animals, thus suggesting that cancer procoagulant could represent a new vitamin K-dependent protein. The biochemical basis for this effect is offered by the identification of gamma-glutamyl carboxylase in the microsomal fraction of tumor tissues. The V2 carcinoma has a carboxylase activity which is increased in warfarin-treated animals. An endogenous substrate of tumor carboxylase, the nature of which has not been identified, has been found 5-fold increased in warfarin-treated animals. The presence of gamma-glutamyl carboxylase was also described in several murine tumors including both carcinomas and fibrosarcomas. It is worth mentioning that all the tumors tested produce a procoagulant with the peculiar characteristics of that described in V2 carcinoma. It is conceivable that cancer procoagulant could represent at least one of the substrates for gamma-glutamyl carboxylase in these experimental tumor tissues.

Animals↗
PubMed1985

Discovery of a gamma-carboxyglutamic acid-containing protein in human spermatozoa.

Here we describe the identification of a gamma-carboxyglutamic acid-containing protein in human spermatozoa. After thermal decarboxylation the protein is a good substrate for vitamin K-dependent carboxylase from various origins. A quick purification procedure for the decarboxylated protein is presented and in a preliminary characterization we have established its Mr (28 000-30 000) and its amino acid composition.

1-Carboxyglutamic Acid↗
PubMed1985

Vitamin K-dependent carboxylase: the carboxylation of exogenous substrates in different systems.

Two types of solid-phase carboxylase, SPC-II and SPC-X, have been prepared from the livers of warfarin-treated cows. Their enzymatic activities were compared with substrate-free carboxylase in microsomes from normal cows and substrate-bound carboxylase in microsomes from warfarin-treated cows. A number of exogenous substrates for carboxylase have been purified and tested. We found that large substrates, such as descarboxyprothrombin, are carboxylated only by substrate-free carboxylase and not by the substrate-bound enzyme. No differences in apparent Km values between solid-phase carboxylases II and X were observed.

Animals↗
PubMed1985

Isoenzymes of vitamin-K-dependent carboxylase.

Vitamin-K-dependent carboxylase was prepared from bovine liver, kidney, lung and testis and it was checked that these systems obeyed the laws of normal enzyme kinetics. Four carboxylatable substrates were obtained from different sources and the apparent Michaelis constants of the various carboxylases for these four substrates were measured. From the results thus obtained we concluded that carboxylase is a group name for a number of isoenzymes which are present in hepatic as well as in various non-hepatic tissues.

Animals↗
PubMed1985

Vitamin K-dependent carboxylase.

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.

1-Carboxyglutamic Acid↗
PubMed1984

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.

1-Carboxyglutamic Acid↗
PubMed1984

Decarboxylated bone Gla-protein as a substrate for hepatic vitamin K-dependent carboxylase.

Bovine bone Gla-protein (B.G.P.) was prepared and decarboxylated into descarboxy-B.G.P. (d-B.G.P.). The latter was purified and identified as decarboxylated osteocalcin. Both crude and purified d-B.G.P. are good substrates for vitamin K-dependent carboxylase. Because the Km of this enzyme for d-B.G.P. is low, the latter is a better substrate than the frequently used pentapeptide FLEEL or exogenous protein substrates such as descarboxyprothrombin.

Ammonium Sulfate↗
PubMed1984

The vitamin K-dependent carboxylation reaction.

Gammacarboxyglutamic acid (Gla) is an abnormal amino acid, which occurs in a number of proteins. It was discovered about 10 years ago in the four vitamin K-dependent blood clotting factors and it could be demonstrated that Gla is formed in a post-translational modification step, which requires a carboxylating enzyme system (carboxylase) and vitamin K. Since at the time of this discovery the earlier mentioned clotting factors were the only proteins known to be synthesized in a vitamin K-dependent way, it has been assumed for many years that the blood clotting system was unique in this respect. Recently it has been demonstrated, however, that vitamin K-dependent carboxylase is not restricted to the liver (the place of synthesis of the clotting factors) but that it is also present in other tissues such as lung, kidney, spleen and testis. Moreover, numerous Gla-containing proteins have been detected, although in most cases their function is not wholly understood. It seems that (like for instance the glycosylation) the vitamin K-dependent carboxylation is a normal post-translational modification, which is required for the correct function of a certain class of Ca2+-binding proteins.

1-Carboxyglutamic Acid↗
PubMed1984

The separation of bovine prothrombin and descarboxyprothrombin by high-performance liquid chromatography.

Prothrombin contains 10 gamma-carboxyglutamic acid (Gla) residues which are absent in the warfarin-induced descarboxyprothrombin; hence prothrombin has 10 more negative groups than has descarboxyprothrombin. The two proteins can be separated by HPLC with the aid of an anion-exchange column. Plasma from warfarin-treated animals could be analyzed without pretreatment of the samples and a full analysis was obtained in 30 min.

Animals↗
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↗