Binding of monofluorophosphate to α2-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: α₂-macroglobulin and C3 (a β-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified α₂-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 α₂-macroglobulin activity was observed 2 hours after intake. Clearance of protein-bound MFP coincided with the return of α₂-macro-globulin to basal levels. [ABSTRACT FROM AUTHOR]