Cyanide binding to human plasma heme-hemopexin: a comparative study

Hemopexin (HPX) displays a pivotal role in heme scavenging and delivery to the liver. In turn, heme-Fe-hemopexin (HPX-heme-Fe) displays heme-based spectroscopic and reactivity properties. Here, kinetics and thermodynamics of cyanide binding to ferric and ferrous hexa-coordinate human plasma HPXheme-Fe (HHPX-heme-Fe(III) and HHPX-heme-Fe(11), respectively), and for the dithionite-mediated reduction of the HHPX-heme-Fe(III)-cyanide complex, at pH 7.4 and 20.0 C, are reported. Values of thermodynamic and kinetic parameters for cyanide binding to HFIPX-heme-Fe(111) and HHPX-herneFe(II) are K= (4.1 +/- 0.4) x 10(-6) M. = (6.9 +/- 0.5) x 10(1) M-1 s(-1) and k(off) = 2.8 x 10(-4) s(-1); and H = (6 +/- 1) x 10(-1) M, h(on) = 1.2 x 10(-1) M-1 s(-1), and h(off) = (7.1 +/- 0.8) x 10(-2) s(-1), respectively. The value of the rate constant for the dithionite-mediated reduction of the HHPX-heme-Fe(II1)-cyanide complex is l = 8.9 0.8 M-1/2 s(-1). HHPX-heme-Fe reactivity is modulated by proton acceptor/donor amino acid residue(s) (e.g., His236) assisting the deprotonation and protonation of the incoming and outgoing ligand, respectively.