The mechanism of iron transferrin interactions. Uptake of the iron nitrilotriacetic acid complex

Abstract

The role of the protonation of the transferrin amino acid ligands involved in complex formation with iron in the presence of nitrilotriacetate has been elucidated. The C-terminal site of transferrin binds to Fe(nta) to produce FeH₃T_c; second-order rate constant k₁=(7.00 ± 0.05)× 10³ dm³ mol^–1 s^–1, stability constant K₁(1.00 ± 0.10)× 10^–5 mol dm^–3. This lowers the deprotonation pK_a of probably the phenolic side-chain of one tyrosine which loses a proton and, thereby, leads to FeH₂T_c; dissociation constant K_1a=(4.50 ± 0.50)× 10^–7 mol dm^–3 and a possible complex stability constant K₁′≈ 2.3 × 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 constant k_2a=(4.50 ± 0.30)× 10⁶ dm³ mol^–1 s^–1, a reverse rate constant k_–2= 0.40 ± 0.05 s^–1, proton dissociation constant K_2a=(8.5 ± 1.1)× 10^–8 mol dm^–3. It remains to be shown whether this slow proton transfer controls a change of the conformation of the binding site or if it occurs because of the particular conformations of the binding sites in neutral media.