Tissue factor (coagulation factor III) inhibition by apolipoprotein A-II

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Abstract

Apolipoprotein A-II (apoA-II) has been shown to inhibit tissue factor participation in the activation of coagulation factor X by factor VIIa. The magnitude of inhibition was dependent on the concentration of the enzyme (factor VIIa) and substrate (factor X) present in the reaction. With factor VIIa at 0.86 nM, 0.41 μM apoA-II inhibited factor X activation as much as 50% at 200 nM factor X, with inhibition decreasing to 39% at 3 nM factor X. When factor X was held constant at 100 nM, 0.41 μM apoA-II inhibited its activation by 80% when factor VIIa was present at 26.7 pM, but the inhibition decreased to 47% when factor VIIa was increased to 1.75 nM. Kinetically, increasing apoA-II decreased the reaction V(max.). ApoA-II produced little effect on the apparent K(m), but the apparent K( 1/2 ) for factor VIIa in the reaction increased as apoA-II concentration increased. In the presence of 0.75 pM bovine tissue factor, reconstituted with 4.31 μM phosphatidylserine-phosphatidylcholine (30:70, w/w) vesicles, and in the absence of apoA-II, the apparent K(m) was near 7 nM factor X when factor VIIa was present at 0.86 nM. Under the same conditions with factor X at 100 nM, the apparent K( 1/2 ) was near 56 pM factor VIIa. As apoA-II was added to 0.41 μM, the apparent K( 1/2 ) increased to about 200 pM factor VIIa. The aggregate results support a model in which apoA-II inhibits tissue factor potentiation of factor VIIa activity. Because the apparent K( 1/2 ) increases when apoA-II is added, the factor VIIa can apparently protect tissue factor from the effects of apoA-II. Thus, apoA-II appears to inhibit factor X activation by preventing the appropriate association of tissue factor with factor VIIa.

Original languageEnglish (US)
Pages (from-to)718-721
Number of pages4
JournalJournal of Biological Chemistry
Volume262
Issue number2
StatePublished - Jan 1 1987

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Apolipoprotein A-II
Factor VIIa
Thromboplastin
Factor X
Chemical activation
Phosphatidylserines
Phosphatidylcholines

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tissue factor (coagulation factor III) inhibition by apolipoprotein A-II. / Carson, Steven D.

In: Journal of Biological Chemistry, Vol. 262, No. 2, 01.01.1987, p. 718-721.

Research output: Contribution to journalArticle

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title = "Tissue factor (coagulation factor III) inhibition by apolipoprotein A-II",
abstract = "Apolipoprotein A-II (apoA-II) has been shown to inhibit tissue factor participation in the activation of coagulation factor X by factor VIIa. The magnitude of inhibition was dependent on the concentration of the enzyme (factor VIIa) and substrate (factor X) present in the reaction. With factor VIIa at 0.86 nM, 0.41 μM apoA-II inhibited factor X activation as much as 50{\%} at 200 nM factor X, with inhibition decreasing to 39{\%} at 3 nM factor X. When factor X was held constant at 100 nM, 0.41 μM apoA-II inhibited its activation by 80{\%} when factor VIIa was present at 26.7 pM, but the inhibition decreased to 47{\%} when factor VIIa was increased to 1.75 nM. Kinetically, increasing apoA-II decreased the reaction V(max.). ApoA-II produced little effect on the apparent K(m), but the apparent K( 1/2 ) for factor VIIa in the reaction increased as apoA-II concentration increased. In the presence of 0.75 pM bovine tissue factor, reconstituted with 4.31 μM phosphatidylserine-phosphatidylcholine (30:70, w/w) vesicles, and in the absence of apoA-II, the apparent K(m) was near 7 nM factor X when factor VIIa was present at 0.86 nM. Under the same conditions with factor X at 100 nM, the apparent K( 1/2 ) was near 56 pM factor VIIa. As apoA-II was added to 0.41 μM, the apparent K( 1/2 ) increased to about 200 pM factor VIIa. The aggregate results support a model in which apoA-II inhibits tissue factor potentiation of factor VIIa activity. Because the apparent K( 1/2 ) increases when apoA-II is added, the factor VIIa can apparently protect tissue factor from the effects of apoA-II. Thus, apoA-II appears to inhibit factor X activation by preventing the appropriate association of tissue factor with factor VIIa.",
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