title: Inhibition of human blood coagulation factor XIa by C-1 inhibitor.
abstract: The inactivation of activated factor XI (factor XIa) and of its isolated light chain by C-1 inhibitor was studied. Irreversible inhibition was observed in a reaction in which no reversible enzyme-inhibitor complex was formed. The second-order rate constants for the inactivation of factor XIa or its light chain by C-1 inhibitor were 2.3 X 10(3) and 2.7 X 10(3) M-1 s-1, respectively. High molecular weight kininogen did not affect the rate of inactivation. The nature of the complexes formed between factor XIa or its light chain and C-1 inhibitor was studied by using sodium dodecyl sulfate gradient polyacrylamide slab gel electrophoresis. Under nonreducing conditions, two factor XIa-C-1 inhibitor complexes were observed with apparent molecular weights of 230,000 and 300,000. Reduction of these complexes resulted in the formation of a single band with a molecular weight of 130,000. This band is also formed in the reaction of the isolated light chain of factor XIa with C-1 inhibitor. These results demonstrate that two C-1 inhibitor molecules can become bound to the light chains of a factor XIa molecule. In addition, the mechanism of interaction of factor XIa or its isolated light chain with C-1 inhibitor appears identical, and the rate of inactivation of the enzyme by C-1 inhibitor is very similar. Neither the heavy chain of factor XIa nor high molecular weight kininogen is significantly involved in the inactivation of factor XIa by C-1 inhibitor.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Meijers
authors.forename: R A
authors.initials: RA
authors.lastname: Vlooswijk
authors.forename: B N
authors.initials: BN
authors.lastname: Bouma
mesh_terms: D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D004789:Enzyme Activation; D005172:Factor XI / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015945:Factor XIa; D006801:Humans; D007700:Kinetics; D007704:Kininogens / Q000502:physiology; D008970:Molecular Weight
chemical_list: D003174:Complement C1 Inactivator Proteins; D007704:Kininogens; D005172:Factor XI; D015945:Factor XIa