APC-catalyzed and nonproteolytic schemes for factor VIIIa decay.

Heterotrimeric factor VIIIa is represented as A1/A3-C1-C2/A2. A1336 and A2N + A2C represent fragments derived from cleavage of A1 and A2 subunits, respectively. Fragment A2N possesses an A1-interactive site.36 Constants k1 and k2 represent the dissociation and association rate constants, respectively, for reversible interaction of factor VIIIa and A1/A3-C1-C2 dimer plus A2 subunit. Constants k3 and k4 represent initial rate constants for cleavage of factor VIIIa at Arg562 and Arg336, respectively. Constants k5 and k8 represent rate constants for cleavage of A1/A3-C1-C2 to A1336/A3-C1-C2 and are likely equivalent to k4. Constants k6 and k7 represent the association and dissociation rate constants for interaction of fragment A2N with A1/A3-C1-C2 and may be similar to k2 and k1, respectively. Constant k9, the rate constant for cleavage of free A2 by APC, is negligible.13