Model of the function of the protein C anticoagulant pathway. All of the reactions of the coagulation and protein C anticoagulation pathway occur at
membrane surfaces, depicted below the factors. When tissue factor is exposed to blood, factor VIIa binds and the complex activates either factor IX (IX) or
factor X (X). The factor IXa-factor VIIIa complex activates factor X (X) to factor Xa (Xa). The Xa then forms a complex with factor Va to convert
prothrombin (pro) to thrombin (T). T then binds to thrombomodulin (TM) to form the protein C activation complex. Protein C (PC) binds to the endothelial
cell protein C receptor (EPCR), if present, and this complex is activated by the T-TM complex. In the capillary, where there is no EPCR, the protein C is
activated directly by the T-TM complex. Activated protein C (APC) can remain bound to EPCR, but this complex does not seem to be capable of
Source: Anticoagulant Protein C/Thrombomodulin Pathway, The Online Metabolic and Molecular Bases of Inherited Disease
inactivating factor Va, presumably an indication that it is targeted to as yet unidentified alternative substrates. When APC dissociates from EPCR, it can
Citation:SValle
Beaudet
AL,inactivates
Vogelstein factor
B, Kinzler
KW,
Antonarakis
Ballabio
A, Gibson
K, Mitchell
G. The Online
and Molecular
then bind to protein
(PS).D,
This
complex
Va or
factor
VIIIa, thusSE,
shutting
down
T formation
and preventing
bloodMetabolic
clot extension.
Factor
Bases
of
Inherited
Disease;
2014
Available
at:
http://mhmedical.com/
Accessed:
July
31,
2017
VIIIa inactivation is augmented by factor V in a process that also requires protein S. Factor V Leiden, a factor V mutation that impairs the function of the
Copyright
© 2017
McGraw-Hill
Education.
reserved
protein C pathway,
cannot
serve
in this role.
See the All
textrights
for further
discussion. (Modified from Esmon CT: Thrombomodulin as a model of molecular
mechanisms that modulate protease specificity and function at the vessel surface. FASEB 9:946. Used with permission.)