Kinetics and regulation of coagulation factor X activation by intrinsic tenase on phospholipid membranes.
J Theor Biol
; 582: 111757, 2024 04 07.
Article
in En
| MEDLINE
| ID: mdl-38336240
ABSTRACT
BACKGROUND:
Factor X activation by the phospholipid-bound intrinsic tenase complex is a critical membrane-dependent reaction of blood coagulation. Its regulation mechanisms are unclear, and a number of questions regarding diffusional limitation, pathways of assembly and substrate delivery remain open.METHODS:
We develop and analyze here a detailed mechanism-driven computer model of intrinsic tenase on phospholipid surfaces. Three-dimensional reaction-diffusion-advection and stochastic simulations were used where appropriate.RESULTS:
Dynamics of the system was predominantly non-stationary under physiological conditions. In order to describe experimental data, we had to assume both membrane-dependent and solution-dependent delivery of the substrate. The former pathway dominated at low cofactor concentration, while the latter became important at low phospholipid concentration. Factor VIIIa-factor X complex formation was the major pathway of the complex assembly, and the model predicted high affinity for their lipid-dependent interaction. Although the model predicted formation of the diffusion-limited layer of substrate for some conditions, the effects of this limitation on the fXa production were small. Flow accelerated fXa production in a flow reactor model by bringing in fIXa and fVIIIa rather than fX.CONCLUSIONS:
This analysis suggests a concept of intrinsic tenase that is non-stationary, employs several pathways of substrate delivery depending on the conditions, and is not particularly limited by diffusion of the substrate.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phospholipids
/
Factor X
/
Neoplasm Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
J Theor Biol
Year:
2024
Document type:
Article