Kinetic evidence for a role of heme geometry on the modulation of carbon monoxide reactivity in human hemoglobin.
Kinetics of CO binding to human hemoglobin (Hb) has been followed below neutrality. With respect to the behavior observed at pH 7.0, CO binding to deoxy-Hb at pH 2.3 displays a much faster second-order combination rate constant (1.2 x 10(-7) M-1 s-1) and loss of the autocatalytic character of the kinetic progress curve. The spectroscopic features of the transient deoxy-Hb at pH 2.75 indicate the phenomenon to be related to the cleavage of the proximal histidine N epsilon-Fe bond, as reported for monomeric hemoproteins (Coletta, M., Ascenzi, P., Traylor, T. G., and Brunori, M. (1985) J. Biol. Chem. 260, 4151-4155). The faster CO binding rate constant, higher than that characteristic of the R state, cannot be attributed to either (i) an enhanced dimerization of deoxy-Hb at low pH, or (ii) a quaternary switch of the unliganded form to the R0 state. The data indicate that interaction(s) of the heme on the proximal side is crucial in accounting for the difference in the CO binding rate constant between the two quaternary conformations of hemoglobin.
Coletta
M
M
Consiglio Nazionale delle Ricerche Center for Molecular Biology, University of Rome La Sapienza, Italy.
Ascenzi
P
P
Brunori
M
M
D002248:Carbon Monoxide / Q000097:blood*; D002263:Carboxyhemoglobin / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011487:Protein Conformation
D006454:Hemoglobins; D006418:Heme; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin