Binding of monofluorophosphate to alpha2-macroglobulin and C3.
After administering an oral dose of monofluorophosphate (MFP) to human beings or rats, a fraction of the drug appears in plasma that is bound to proteins, establishing a previously undetected compartment of nondiffusible fluoride. This article documents experiments performed in vitro, describing the binding of MFP to two plasma globulins: alpha2-macroglobulin and C3 (a beta-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified alpha2-macroglobulin or to C3 with a molar ratio MFP: protein close to unity. MFP binding reduces significantly the biological activity of these proteins, which share in common a macrocyclic 4-residue ring thiolactone (Cys-Gly-Glu-Glu). The binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma of volunteers during the 5-7 hours following intake. Peak concentration of protein-bound MFP and maximal reduction of alpha2-macroglobulin activity was observed 2 hours after intake. Clearance of protein-bound MFP coincided with the return of alpha2-macroglobulin to basal levels.
Rigalli
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Laboratorio de Biología Osea, Facultad de Ciencias Mèdicas, Universidad Nacional de Rosario, Argentina.
Esteban
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Pera
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Puche
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RC
D000818:Animals; D003176:Complement C3 / Q000378:metabolism*; D005459:Fluorides / Q000378:metabolism*; D006801:Humans; D010710:Phosphates / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D000511:alpha-Macroglobulins / Q000378:metabolism*
D003176:Complement C3; D010710:Phosphates; D000511:alpha-Macroglobulins; C012980:fluorophosphate; D005459:Fluorides