Specific nickel(II)-transfer process between the native sequence peptide representing the nickel(II)-transport site of human serum albumin and L-histidine.

The kinetics and mechanism for Ni(II)-transfer of the native sequence tripeptide, L-aspartyl-L-alanyl-L-histidine-N-methylamide (AAHNMA), representing the Ni(II)-transport site of human serum albumin (HSA) and L-histidine (L-His) was studied in forward and reverse reactions in the pH range 6.5 to 9.0 at I = 0.2 and 25 degrees C. For the Ni(II)-transfer from Ni(II)-(L-His)2 to native sequence peptide, the rate-determining step is the formation of a mixed-ligand complex of NiH-1AB by deprotonation of peptide nitrogen from NiAB where A and B denote the anionic forms of AAHNMA and L-His, respectively. For the Ni(II)-transfer from Ni(II)-peptide to L-His, the rate-determining step is a bond breaking between Ni(II) and peptide nitrogen to form NiH-1A by protonation to a peptide nitrogen of NiH-2A. The equilibrium constants for the metal-transfer reaction of MH-2A + 2HB in equilibrium MB2 + A (A = Ni(II), Cu(II] were 10(3.29) and 10(0.78) for Ni(II) and Cu(II), respectively. NiB2 is 324 times as stable as CuB2. Furthermore, the ratio of Ni(II)/Cu(II) in the rate constants for the reaction of MB2 with A was found to be 2.8 x 10(-4). Thus, despite the similarities of Cu(II) and Ni(II) in the metal-binding sites of HSA and in reaction mechanism, Ni(II)-(L-His)2 complex is so stable thermodynamically and kinetically, compared to the Cu(II)-(L-His)2 complex, that Ni(II) is hardly transferred from Ni(II)-(L-His)2 to native sequence peptide. These findings may support specificities in the Ni(II)-transfer, its organ distribution, and its excretion through urine in vivo.