THE MECHANISM OF IRON TRANSFERRIN INTERACTIONS - UPTAKE OF THE IRON NITRILOTRIACETIC ACID COMPLEX

The role of the protonation of the transferrin amino acid ligands invo lved in complex formation with iron in the presence of nitrilotriaceta te has been elucidated. The C-terminal site of transferrin binds to Fe (nta) to produce FeH3Tc; second-order rate constant k1 = (7.00 +/- 0.0 5) x 10(3) dm3 mol-1 s-1, stability constant K1 (1.00 +/- 0.10) x 10(- 5) mol dm-3. This lowers the deprotonation pK(a) of probably the pheno lic side-chain of one tyrosine which loses a proton and, thereby, lead s to FeH2Tc; dissociation constant K1a = (4.50 +/- 0.50) x 10(-7) mol dm-3 and a possible complex stability constant K1' almost-equal-to 2.3 x 10(-9) mol dm-3. As for the N-terminal site, it binds to Fe(nta) by a process controlled by a slow proton transfer; second-order rate con stant k2a = (4.50 +/- 0.30) x 10(6) dm3 mol-1 s-1, a reverse rate cons tant k-2 = 0.40 +/- 0.05 s-1, proton dissociation constant K2a = (8.5 +/- 1.1 ) x 10(-8) mol dm-3. It remains to be shown whether this slow proton transfer controls a change of the conformation of the binding s ite or if it occurs because of the particular conformations of the bin ding sites in neutral media.