Interaction of hementin with fibrinogen and fibrin.
The giant Amazon leech Haementeria ghilianii manufactures blood anticoagulant which is present in the posterior and anterior salivary glands. The mechanism of blood anticoagulation by Haementeria ghilianii is completely different from that used by Hirudo medicinalis. The anticoagulant is mostly associated with a fibrinogen-degrading proteinase, hementin. However, other inhibitors of blood coagulation are also present in the salivary glands. The salivary gland extract inhibits platelet aggregation that is mostly attributable to the degradation of fibrinogen. Hementin purified by various methods has a molecular weight in the range of 80,000-120,000 and appears to be a metalloproteinase that is regulated by calcium ions. The enzyme degrades both fibrinogen and fibrin. The Michaelis constant for human fibrinogen is 1 microM. The cleavage of the isolated chains of fibrinogen is inefficient implying that the native conformation of the substrate may play a role in the recognition mechanism. The pattern of fibrinogen degradation by hementin resembles that caused by plasmin since products analogous to fragments Y, D and E are generated. However, the unique action of hementin on fibrinogen is in the initial proteolytic attack in the coiled-coil connector region while proteolysis of the alpha-chain is very slow. In consequence, unique fibrinogen fragments are formed that contain the entire COOH-terminus of the alpha-chain. The mechanism of blood anticoagulation by hementin is very efficient since the cleavage of only three peptide bonds in the fibrinogen molecule disassembles its bivalent structure and renders it non-functional.
Budzynski
A Z
AZ
Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.
D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007865:Leeches / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism*
D000925:Anticoagulants; D005337:Fibrin; D005340:Fibrinogen; D008666:Metalloendopeptidases; C040192:hementin; D002118:Calcium