| pubmed-article:9468488 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C0205101 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C0164707 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C0015520 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:9468488 | lifeskim:mentions | umls-concept:C1522492 | lld:lifeskim |
| pubmed-article:9468488 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:9468488 | pubmed:dateCreated | 1998-3-19 | lld:pubmed |
| pubmed-article:9468488 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:9468488 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9468488 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9468488 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9468488 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9468488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9468488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:9468488 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9468488 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:9468488 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:9468488 | pubmed:author | pubmed-author:BaughR JRJ | lld:pubmed |
| pubmed-article:9468488 | pubmed:author | pubmed-author:KrishnaswamyS... | lld:pubmed |
| pubmed-article:9468488 | pubmed:author | pubmed-author:BrozeG JGJJr | lld:pubmed |
| pubmed-article:9468488 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9468488 | pubmed:day | 20 | lld:pubmed |
| pubmed-article:9468488 | pubmed:volume | 273 | lld:pubmed |
| pubmed-article:9468488 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9468488 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9468488 | pubmed:pagination | 4378-86 | lld:pubmed |
| pubmed-article:9468488 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:meshHeading | pubmed-meshheading:9468488-... | lld:pubmed |
| pubmed-article:9468488 | pubmed:year | 1998 | lld:pubmed |
| pubmed-article:9468488 | pubmed:articleTitle | Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor. | lld:pubmed |
| pubmed-article:9468488 | pubmed:affiliation | Department of Medicine, Division of Hematology/Oncology, Emory University, Atlanta, Georgia 30322, USA. | lld:pubmed |
| pubmed-article:9468488 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:9468488 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:9468488 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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