Fibrinogen degradation by hementin, a fibrinogenolytic anticoagulant from the salivary glands of the leech Haementeria ghilianii
Research article published in The Journal of laboratory and clinical medicine (1984)
Abstract
The leech Haementeria ghilianii contains the anticoagulant hementin in its salivary glands, which renders ingested blood incoagulable. The loss of thrombin-coagulability of human fibrinogen, plasma, and blood was dependent on both dose and time, and it was attributable to direct proteolytic degradation of fibrinogen (Mr 340,000) by hementin. Using purified fibrinogen as the substrate, it was demonstrated that the enzyme cleaved with equal probability either through all three chains in the connector region between the D and E structural domains or in the COOH-terminal of the A alpha chain. The degradation pattern of fibrinogen in blood and purified counterpart was the same in respect to the types of degradation products formed and the rate of proteolysis. Three pairs of fibrinogen degradation products characterized by Mr were distinguished: 320,000 and 300,000, 225,000 and 200,000, 157,000 and 132,000. In each pair, the heavier product had the intact COOH-terminals of the A alpha, B beta, and gamma chains. Of special interest was the derivative of Mr 225,000 because it contained the intact A alpha, B beta, and gamma chains of the original fibrinogen. Hementin cleaved non-cross-linked and cross-linked fibrin clots; however, the rate of proteolysis was much slower than that of fibrinogen. Individual carboxymethylated chains of fibrinogen were not degraded by the enzyme. Hementin abolished coagulability of fibrinogen by a limited proteolysis that disassembled functionally bivalent polymerization sites. In addition, fibrin clot formation was inhibited by fibrinogen fragments generated by hementin. The enzyme appeared to have a unique and limited specificity for a few peptide bonds projected in the tertiary structure of the native fibrinogen molecule.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Peer-reviewed clinical and outcomes research relevant to medicinal leech therapy and its biology. Indexed in PubMed and verified against the NCBI record.
Почему это важно для гирудотерапии
Это биохимическое исследование in vitro (Malinconico et al., 1984) охарактеризовало гементин — антикоагулянт из слюнных желёз пиявки Haementeria ghilianii, показав, что он устраняет тромбин-обусловленную свёртываемость человеческого фибриногена, плазмы и крови посредством дозо- и время-зависимого прямого протеолитического расщепления фибриногена, а не через ингибирование тромбина, и что он также способен лизировать не-сшитые и сшитые фибриновые сгустки, хотя и медленнее. Это основополагающая запись в истории поиска лекарств на основе секретома медицинских пиявок, документирующая фибриногенолитический механизм, отличный от ингибиторов тромбина hirudin-типа, более привычных по Hirudo medicinalis, и иллюстрирующая химическое разнообразие антикоагулянтов пиявочного происхождения. Оговорка: это эксперименты с очищенным ферментом и на крови ex vivo от немедицинского вида пиявок, без данных на животных или клинических данных, поэтому выводы говорят о механизме и потенциале для поиска лекарств, а не о клинической гирудотерапии.
Цитирование
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
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