Mechanism of Action of Factor D of the Alternative Complement
نویسندگان
چکیده
Factor D, also referred to as C3 proactivator convertase, constitutes the activating enzyme of the C3 convertase of the alternative pathway (2) . As such, it is an essential component of initiation and amplification of the pathway (3, 4) . The enzyme cleaves factor B, or C3 proactivator, into the activation fragment Ba (30,000 daltons) and the active site bearing fragment Bb (62,000 daltons) (5, 6) . This reaction proceeds only when factor B is in Mg"-dependent association with C3b and results in the formation of C3b,Bb which is endowed with C3 cleaving activity (2, 7) . Unlike other alternative pathway components, factor D has escaped unequivocal elucidation as to its mode of action, probably because it is a trace protein in human serum and its function is mimicked by certain tryptic enzymes which are unrelated to complement . Uncertainty persists as to whether factor D (a) is absolutely required for C3/C5 convertase formation, (b) is physically incorporated into this multimolecular enzyme, and (c) occurs in plasma and serum in zymogen form, in which case the mode of activation is unknown . We wish to report that factor D occurs in human plasma and serum only as an active enzyme and that it is absolutely required for C3/C5 convertase formation under physiological conditions without becoming a subunit of this complex enzyme . Thus, factor D, which is responsible for the first enzymatic event of the alternative pathway, necessitates no activation and is subject to no consumption . Its function depends entirely upon proper presentation of its substrate . It may be of biomedical significance that the enzyme that plays an essential role in the initiation and amplification of the alternative pathway is available in the circulation of the host in active form only .
منابع مشابه
Mechanism of action of factor D of the alternative complement pathway
Factor D (C3 proactivator convertase) of human serum has been shown to be absolutely necessary for alternative pathway function, for activation of the C3/C5 convertase of that pathway and not to be a subunit of this enzyme. Factor D was found to be present in human plasma in active form only, at a concentration of 2 microgram/ml, and not to be controlled by plasma protease inhibitors or by spon...
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