Tension'' on Heme by the Proximal Base and Ligand Reactivity: Conclusions Drawn from Model Compounds for the Reaction of Hemoglobin

• Published in: Proceedings of the National Academy of Sciences - PNAS 1978-08, Vol.75 (8), p.3747-3750
• Main Authors: Sharma, V. S., Geibel, J. F., Ranney, H. M.
• Format: Article
• Language: English
• Subjects: Carbon Monoxide; Chemical bases; Combination rates; Heme; Hemoglobins; Iron; Kinetics; Ligands; Models, Chemical; Nitric Oxide; Oxygen; Phosphates; Porphyrins; Reactivity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.75.8.3747

The kinetic data on model compounds of hemoglobin indicate that in oxy derivatives ligand dissociation rates are sensitive to the ``tension'' exerted by the proximal base on the metal-to-ligand bond; the corresponding rates for carboxy derivatives are not sensitive to the tension. It is suggested that the metal-to-ligand bond becomes weaker with increased ``pull'' (or tension) on Fe from the proximal base due to the steric and/or electronic interaction between the ligand, the porphyrin ring, and the proximal base. In model compounds the linear heme Fe-to-CO bond vis-a-vis the bent heme Fe-to-O2bond probably makes such interactions less significant in carboxy derivatives. It is proposed that the kinetic α ,β -chain nonequivalence in Hb4(O2)4is due to the difference in the tension in the two chains on Fe by the proximal base. The absence of α ,β -chain differences large enough to show up in CO dissociation rates from Hb4(CO)4is explained on the basis of lack of sensitivity of the Fe-CO bond to tension from the proximal base. The implications of the results for the observed cooperative effects in ligand combination (for CO) and dissociation (for O2and NO) rates of hemoglobin have also been discussed.