Flow dependence of factor X activation by tissue factor-factor VIIa.
Blood coagulation is initiated after blood is exposed to the transmembrane glycoprotein Tissue Factor (TF). The continuous flow reactor has been used to study the flow-dependent activation of factor X by the complex of TF and factor VIIa. The apparent Km value of X for TF-VIIa in vesicles of 16 nM is low compared to the value of > 600 nM on a macroscopic surface. At 17 to 70 fmoles TF-VIIa/cm2, the steady state Xa production rate was fairly insensitive to the enzyme density, which is in contrast with classical Michaelis-Menten kinetics. The X activation rate was linear with the cube root of the flow rate. These results show that X activation is limited by transport of factor X across a boundary layer towards the enzyme complex.
Contino
P B
PB
Department of Medicine, Mount Sinai School of Medicine of the City University of New York, N.Y.
Andree
H A
HA
Nemerson
Y
Y
D001775:Blood Circulation / Q000502:physiology*; D001777:Blood Coagulation / Q000187:drug effects; D004058:Diffusion; D004789:Enzyme Activation / Q000187:drug effects; D004800:Enzymes, Immobilized; D015942:Factor VIIa / Q000494:pharmacology*; D005170:Factor X / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D010743:Phospholipids / Q000737:chemistry; D013925:Thromboplastin / Q000494:pharmacology*
D004800:Enzymes, Immobilized; D010743:Phospholipids; D005170:Factor X; D013925:Thromboplastin; D015942:Factor VIIa