The Role of High Molecular Weight Kininogen (Fitzgerald Factor) in the Activation of Various Plasma Proteolytic Enzyme Systems

Bovine high molecular weight kininogen (bHMWK) partially corrects the aPTT of Fitzgerald-trait plasma, which is congenitally deficient in HMWK. The relationship between the structure and activity of HMWK was clarified by studying the effects of different fragments of bHMWK on the aPTT of Fitzgerald-trait plasma. The peptides studied, all in equimolar concentrations, were lys-bradykinin-free HMWK, bradyk In In-fragment 1-2-tree HMWK, heavy chain, fragment 1 -2-Hght chain, and light chain. Bradykinin- fragment 1-2-free HMWK, heavy chain, and light chain have little or no correcting activity upon Eitzgeraldtrait plasma aPTT. Fragment 1-2 light chain has the same correcting activity as intact bHMWK, while that of lysbradykinin-free HMWK appears to be higher. Both fragment 1-2 and fragment 2 inhibit the clotting time of normal human plasma. On a molar basis, fragment 2 is a more active inhibitor than fragment 1-2. Bovine plasma kallikrein released kinins from both bHMWK and hHMWK; however, while the correcting activity of bHMWK was completely destroyed after sixty minutes of incubation, that of hHMWK was fully retained. These data suggest that: (1) the active part of bHMWK is comprised of the fragment 1-2 light chain portion; (2) fragment 1-2 or fragment 2 is the binding site to negatively charged surfaces, while the light chain interacts with other components of the surface-mediated reactions; and (3) bovine plasma kallikrein releases kinins but probably does not cause the release of fragment 1-2 from hHMWK