{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=curation_notes.txt"],"Pdf":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.pdf"],"Owl":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359-biopax2.owl","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359-biopax3.owl"],"Svg":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.svg"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=manifest.xml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359_url.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=curation_image.png","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359-matlab.m","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.vcml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.sci","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359-octave.m","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=metadata.rdf","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.png","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359_url.sedml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.ode","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000359?filename=BIOMD0000000359.m"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Michael Schubert"],"curationStatus":["Manually curated"],"modellingApproach":["ordinary differential equation model"],"levelVersion":["L2V4"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/BIOMD0000000359"],"publication_pubmed":["11985578"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["Panteleev2002 TFPImechanism schmema3"],"publication_year":["2002"],"submissionId":["MODEL1108260008"],"publication_authors":["Mikhail A Panteleev, Veronica I Zarnitsina, Fazoil I Ataullakhanov"],"first_author":["Mikhail A Panteleev"],"publication":["11985578,\n                            We have analyzed several mathematical models that describe inhibition of the factor VIIa-tissue factor complex (VIIa-TF) by tissue factor pathway inhibitor (TFPI). At the core of these models is a common mechanism of TFPI action suggesting that only the Xa-TFPI complex is the inhibitor of the extrinsic tenase activity. However, the model based on this hypothesis could not explain well all the available experimental data. Here, we show that a good quantitative description of all experimental data could be achieved in a model that contains two more assumptions. The first assumption is based on the hypothesis originally proposed by Baugh et al. [Baugh, R.J., Broze, G.J. Jr & Krishnaswamy, S. (1998) J. Biol. Chem. 273, 4378-4386], which suggests that TFPI could inhibit the enzyme-product complex Xa-VIIa-TF. The second assumption proposes an interaction between the X-VIIa-TF complex and the factor Xa-TFPI complex. Experiments to test these hypotheses are suggested.. 8, 269.\n                            National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia."],"submitter_mail":["schubert@ebi.ac.uk"],"submitter_affiliation":["EBI"],"publicationId":["BIOMD0000000359"],"pubmed_abstract":["Tissue factor (TF) pathway inhibitor (TFPI) regulates factor X activation through the sequential inhibition of factor Xa and the VIIa.TF complex. Factor Xa formation was studied in a purified, reconstituted system, at plasma concentrations of factor X and TFPI, saturating concentrations of factor VIIa, and increasing concentrations of TF reconstituted into phosphatidylcholine:phosphatidylserine membranes (TF/PCPS) or PC membranes (TF/PC). The initial rate of factor Xa formation was equivalent in the presence or absence of 2.4 nM TFPI. However, reaction extent was small (<20%) relative to that observed in the absence of TFPI, implying the rapid inhibition of VIIa.TF during factor X activation. Initiation of factor Xa formation using increasing concentrations of TF/PCPS or TF/PC in the presence of TFPI yielded families of progress curves where both initial rate and reaction extent were linearly proportional to the concentration of VIIa.TF. These observations were consistent with a kinetic model in which the rate-limiting step represents the initial inhibition of newly formed factor Xa. Numerical analyses of progress curves yielded a rate constant for inhibition of VIIa.TF by Xa.TFPI (>10(8) M-1.s-1) that was substantially greater than the value (7.34 +/- 0.8 x 10(6) M-1.s-1) directly measured. Thus, VIIa.TF is inhibited at near diffusion-limited rates by Xa.TFPI formed during catalysis which cannot be explained by studies of the isolated reaction. We propose that the predominant inhibitory pathway during factor X activation may involve the initial inhibition of factor Xa either bound to or in the near vicinity of VIIa.TF on the membrane surface. As a result, VIIa.TF inhibition is unexpectedly rapid, and the concentration of active factor Xa that escapes regulation is linearly dependent on the availability of TF.","We have analyzed several mathematical models that describe inhibition of the factor VIIa-tissue factor complex (VIIa-TF) by tissue factor pathway inhibitor (TFPI). At the core of these models is a common mechanism of TFPI action suggesting that only the Xa-TFPI complex is the inhibitor of the extrinsic tenase activity. However, the model based on this hypothesis could not explain well all the available experimental data. Here, we show that a good quantitative description of all experimental data could be achieved in a model that contains two more assumptions. The first assumption is based on the hypothesis originally proposed by Baugh et al. [Baugh, R.J., Broze, G.J. Jr & Krishnaswamy, S. (1998) J. Biol. Chem. 273, 4378-4386], which suggests that TFPI could inhibit the enzyme-product complex Xa-VIIa-TF. The second assumption proposes an interaction between the X-VIIa-TF complex and the factor Xa-TFPI complex. Experiments to test these hypotheses are suggested."],"pubmed_title":["Tissue factor pathway inhibitor: a possible mechanism of action.","Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor."],"pubmed_authors":["Baugh R J RJ, Broze G J GJ, Krishnaswamy S S","Panteleev Mikhail A MA, Zarnitsina Veronica I VI, Ataullakhanov Fazoil I FI"],"additional_accession":[]},"is_claimable":false,"name":"Panteleev2002_TFPImechanism_schmema3","description":"\n      \n        This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.\nFor more information see the terms of use.\nTo cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.\n      \n    \n  ","dates":{"last_modification":"2024-08-21","publication":"2024-09-02","submission":"2011-08-26"},"accession":"BIOMD0000000359","cross_references":{"pubmed":["11985578","9468488"],"biomodels__db":["MODEL1108260008","BIOMD0000000359"],"go":["GO:0007596"],"taxonomy":["2759"],"uniprot":["P13726","P08709","P00742","P10646"]}}