-------► Activated Factor X +
1 4 3
1 9 5
4 4 8
T_________I __ I________
■ ■ ■
C H A P T E R 3 6 , F IG U R E 12
Activation of factor X. Factor X is
activated by factor Vila through a single peptide bond cleavage,
Arg5I-IIe52 in the heavy chain of the proenzyme. The activation peptide
is highly glycosylated as are many of the activation peptides of the pro-
coagulant proenzymes. Factor X is converted to factor Xa by factor IXa
through cleavage of the same peptide bond that is cleaved by Factor
Vila. Motifs and domains are color coded as follows: Gla domain (blue),
EGF-like domain (magenta), activation peptide (yellow), and proteinase
domain (green). Light chains are indicated in dark gray, heavy chains in
light gray. Regions connecting the motifs are black.
F a cto r IX —
► F a cto r IXa + P e p tid e
1 8 0
4 1 5
■ ■ ■
C H A P T E R 3 6 , F I G U R E 1 3
Activation of factor IX. Factor IX is acti-
vated by cleavage of two peptide bonds, Arg145 and Arg180-Val181. The acti-
vation peptide that is released is composed of 35 amino acid residues and is
highly glycosylated. The same peptide bonds are cleaved by factor Vila and
factor XIa. Glycosaminoglycans, particularly heparin, can increase the rate
of activation as the result of the binding of both factor XIa and factor IX to
the heparin molecule to form a ternary complex. Color coding is as
described in Figure 36-12.
C H A P T E R 3 6 , F I G U R E 14
Contact phase of
coagulation. The contact phase reactions involve two pro-
teinase precursors—factor XII and prekallikrein—and one cofactor protein—plasma high-molecular-weight kininogen
(HAWK). The structures, in bar diagrams, show the presence of EGF-like fibronectin type I and type II, kringle, cys-
tatin-like, and “apple” motifs. The cleavage site for proteolytic activation of factor XII is Arg353 and for prekallikrein
Arg371. The cofactor protein, HMWK, is cleaved by kallikrein at Arg362 and Arg371 to release bradykinin (yellow).
HMWK contains a unique His-rich region that is associated with binding to the contact surface (shown in light blue).
Factor XI is a dimer of two identical polypeptide chains that are linked by a single disulfide bridge. In the circulating
blood, factor Xlla cleaves the two Arg369Tle370 peptide bonds in factor XI to form factor XIa. Other motifs and
domains are color coded as follows: apple domains (cyan), EGF-like motifs (magenta), fibronectin motifs (yellow),
kringle (orange), and proteinase domain (green). Light chains are indicated in dark gray, heavy chains in light gray.
Regions connecting the motifs are black.