Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1988-8-8
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
263
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9994-10001
pubmed:dateRevised
2007-11-14
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
pubmed:year
1988
pubmed:articleTitle
Early processing of prothrombin and factor X by the vitamin K-dependent carboxylase.
pubmed:affiliation
Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.