Abstract
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.
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Rigalli, A., Esteban, L., Pera, L. et al. Binding of monofluorophosphate to α2-macroglobulin and C3. Calcif Tissue Int 60, 86–89 (1997). https://doi.org/10.1007/s002239900190
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DOI: https://doi.org/10.1007/s002239900190