ISSN:1424-8832    

DOI:10.1159/000215290

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215291

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215292

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Vitamin K is required as a cofactor for a microsomal enzyme that converts glutamyl residues in precursor proteins to γ-carboxyglutamyl residues in completed proteins. These residues are essential for the biological function of prothrombin, factors VII, IX, and X, protein C, and protein S. Current data suggest that recognition of protein substrates by the carboxylase requires an unidentified protein-protein interaction in addition to the Glu substrate binding site. The primary vitamin K-dependent event has now been shown to be the abstraction of the γ-hydrogen of the substrate Glu residue with the concurrent formation of vitamin K 2,3-epoxide. Coumarin anticoagulants appear to inhibit the microsomal vitamin K epoxide reductase and one of a number of microsomal quinone reductases. They therefore block vitamin K action by preventing the recycling of vitamin K epoxide to the quinone and to the active cofactor form, the hydroquinone. Excess vitamin K can reverse a coumarin anticoagulant effect as the nonsensitive quinone reductase can continue to furnish the active coenzym

ISSN:1424-8832    

DOI:10.1159/000215293

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Kinetic studies of prothrombin activation and intrinsic factor X activation carried out in the absence and presence of phospholipids and the protein cofactors Va or Villa have provided insight in the mechanism by which the accessory components enhance coagulation factor activation. In intrinsic factor X and prothrombin activation, phospholipids cause a drastic drop of Km for the substrates factor X and prothrombin, whereas the protein cofactors factor Va and factor Villa increase Vmax of the prothrombin- and factor X-activating reactions. The mode of action of factor Va in prothrombin activation is however somewhat more complex. Besides its stimulatory effect on the catalytic activity of factor Xa, Factor Va also plays an important role in the assembly of the prothrombin-activating complex at phospholipid surfaces especially when the latter have a low affinity for vitamin-K-dependent coagulation factors. This effect is likely accomplished by promoting the binding of both prothrombin and factor Xa to the procoagulant surface.

ISSN:1424-8832    

DOI:10.1159/000215294

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Using recombinant DNA techniques, DNA fragments coding for bovine prothrombin mRNA have been cloned and characterized. Structural studies have revealed that prothrombin mRNA encodes a precursor protein having an amino-terminal extension of 43 amino acid residues. Using bovine prothrombin cDNA as a hybridization probe, the genes coding for human and bovine prothrombin have been isolated and partially characterized. The organization of the prothrombin gene is similar, but not identical to the organization of the genes coding for the other vitamin-K-dependent clotting factors.

ISSN:1424-8832    

DOI:10.1159/000215295

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

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 isoenzy

ISSN:1424-8832    

DOI:10.1159/000215296

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

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 (16mg/l) in human urine is well above the concentration required for the in vitro inhibition of salt precipitat

ISSN:1424-8832    

DOI:10.1159/000215297

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Osteocalcin is an abundant Ca2+-binding protein indigenous to the organic matrix of bone, dentin, and possibly other mineralized tissues. This protein contains 47–50 amino acid residues (molecular weight 5,200–5,900) depending on the species. Osteocalcin is distinguished by its content of three gamma-carboxyglutamic (Gla) residues. The vitamin-K-dependent biosynthesis of osteocalcin occurs in bone, and the protein is not homologous to the Gla-containing regions of known vitamin-K-dependent blood coagulation proteins. The two major structural features of osteocalcin which appear to control its function include: (1) the ‘Gla helix’, a compact Ca2+-dependent alpha-helical conformation, in which the three Gla residues are aligned to facilitate adsorption to hydroxyapatite, and (2) the ‘COOH-terminal beta-sheet’ which exhibits chemoattractant activity toward mononuclear leukocytes, specifically monocytes, the putative precursors of osteoclasts. While the biological function of osteocalcin is unknown, it appears to be a highly specific osteoblastic marker produced during bone formation, and is rapidly becoming a clinically important diagnostic parameter of bone pathology. This article reviews recent advances in the understanding of

ISSN:1424-8832    

DOI:10.1159/000215298

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Tumor cells are known to interfere with blood coagulation pathways of the host by producing procoagulants and other substances, thereby deriving certain advantages relating to tumor growth, metastasis, and angiogenesis. Anticoagulants may diminish these advantages under certain conditions. The interaction between coumarin anticoagulants and tumor cells has been reviewed with respect to procoagulants and their vitamin K-dependent properties. Evidence is also presented which suggests that vitamin K-dependent protein carboxylation is a general property of tumor cells.

ISSN:1424-8832    

DOI:10.1159/000215299

出版商:S. Karger AG    

年代:1986

数据来源: Karger