Coagulation Party - FXII, HNWK, PK

[Gammon1]

Factor XII is a contact factor which autoactivates on negatively charged surfaces *in the presence of PK and HMWK.* It activates prekallikrein to kallikrein, which in turn cleaves High Molecular Weight Kininogen to liberate bradykinin.

FXII may then go on to activate factor XI.

However, I also read PK can cleave HMWK, and that HMWK may be surface bound.

It's all rather confusing when material states that PK/HMWK as well as FXI/HMWK circulate as complexes in the blood as 1:1 and 1:2 molecule ratios, respectively.

So, to my question. Could one of you fine ladies and/or gentlemen please put the contact pathway into a sensible order for me, separating the factor XII dependent and independent activation of the kallikrein-kinin system?

*Side questions:

1. If HMWK bound PK or FXI is activated, will they separate from the HMWK?

2. Are FXII, PK, and HMWK bound as a complex, and if so what does it look like?

3. If HMWK can be surface bound, is it bound as a complex or as a single molecule - and if the latter is the case, is there any rebinding with PK?

4. When stated that FXII is activated *in the presence of* PK and HMWK - what exactly does this mean?

It seems to imply that theres no binding going on, but if so, where is the interaction?

Disclaimer: I am a self studying student with a very weak base in Chemistry, so forgive my ignorance.

Huge thanks in advance.