BINDING OF MONOFLUOROPHOSPHATE TO ALPHA(2)-MACROGLOBULIN AND C3

After administering an oral dose of monofluorophosphate (MFP) to human beings or mts, a fraction of the drug appears in plasma that is bound to proteins, establishing a previously undetected compartment of nond iffusible fluoride. This article documents experiments performed in vi tro, describing the binding of MFP to two plasma globulins: alpha(2)-m acroglobulin and C3 (a beta-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified alpha(2)-macrog lobulin or to C3 with a molar ratio MFP: protein close to unity. MFP b inding reduces significantly the biological activity of these proteins , which share in common a macrocyclic 4-residue ring thiolactone (Cys- Gly-GIu-Glu). The binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma of volunteers during the 5-7 hours followi ng intake. Peak concentration of protein-bound MFP and maximal reducti on of alpha(2)-macroglobulin activity was observed 2 hours after intak e. Clearance of protein-bound MFP coincided with the return of alpha(2 )-macroglobulin to basal levels.