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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
20
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pubmed:dateCreated |
1988-8-8
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pubmed:abstractText |
Binding interactions between the membrane-associated vitamin K-dependent carboxylase and its prothrombin and factor X substrates have been investigated in liver microsomes. Both substrates are firmly attached to microsomal membrane fragments which also harbor the carboxylase. In vitro 14CO2 gamma-carboxylation of these substrates, triggered by reduced vitamin K1H2, resulted in release of 14C-labeled prothrombin precursors from the membrane fragments, but no release of 14C-labeled factor X precursors could be demonstrated, which suggested a difference in early processing of these substrates by the carboxylase. Warfarin treatment of rats resulted in a 3-fold increase in the membrane concentration of factor X antigens and a 20-fold increase in 14C gamma-carboxylation of the membrane pool of factor X carboxylase substrates. There was a dose-response relationship between the amount of drug administered to the rats and 14C labeling of the membrane pool of factor X carboxylase substrates. On the other hand, the membrane concentration of prothrombin antigens did not increase in response to the drug, and 14CO2 gamma-carboxylation of the membrane pool of prothrombin carboxylase substrates was the same in warfarin and saline-treated rats. The results demonstrate significant differences in the interaction between the carboxylase and its prothrombin and factor X substrates. It appears that the different interactions result from binding of the prothrombin and the factor X precursors to separate microsomal membrane proteins that are involved in the gamma-carboxylation reaction. Warfarin appears to induce the factor X precursor-specific but not the prothrombin precursor-specific binding proteins, which suggests a new mechanism for the action of warfarin. These binding proteins may be under different genetic control. Treatment of the prothrombin and the factor X carboxylase substrates with endonuclease H showed that the rat prothrombin and the human factor X carboxylase substrates are high mannose glycoproteins. The human prothrombin and the rat factor X carboxylase substrates did not, on the other hand, change their migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels after endonuclease H treatment. The data demonstrate differences in the glycoprotein nature of the rat and the human carboxylase substrates.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-((3-cholamidopropyl)dimethylammoni...,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Carbon Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Cholic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Factor X,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hexosaminidases,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Mannose,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Prothrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Warfarin,
http://linkedlifedata.com/resource/pubmed/chemical/glutamyl carboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/imidazole
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9994-10001
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3290218-Animals,
pubmed-meshheading:3290218-Buffers,
pubmed-meshheading:3290218-Carbon-Carbon Ligases,
pubmed-meshheading:3290218-Cholic Acids,
pubmed-meshheading:3290218-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:3290218-Factor X,
pubmed-meshheading:3290218-Glycoproteins,
pubmed-meshheading:3290218-Hexosaminidases,
pubmed-meshheading:3290218-Humans,
pubmed-meshheading:3290218-Imidazoles,
pubmed-meshheading:3290218-Immunoassay,
pubmed-meshheading:3290218-Immunosorbent Techniques,
pubmed-meshheading:3290218-Ligases,
pubmed-meshheading:3290218-Male,
pubmed-meshheading:3290218-Mannose,
pubmed-meshheading:3290218-Microsomes, Liver,
pubmed-meshheading:3290218-Molecular Weight,
pubmed-meshheading:3290218-Peptide Fragments,
pubmed-meshheading:3290218-Protein Precursors,
pubmed-meshheading:3290218-Prothrombin,
pubmed-meshheading:3290218-Rats,
pubmed-meshheading:3290218-Warfarin
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pubmed:year |
1988
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pubmed:articleTitle |
Early processing of prothrombin and factor X by the vitamin K-dependent carboxylase.
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pubmed:affiliation |
Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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