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I have studied this in almost every physiology book but I just can't understand how carbon monoxide can affect oxygen's affinity to Hemoglobin. I know that there is left shift in oxygen dissociation curve but why?

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Affinity for any ligand to a protein is a function of the shape of the protein which provides some place for the ligand to bind/interact.

Hemoglobin typically exists in tetrameric form: it is a collection of 4 subunits that each bind 1 molecule of oxygen.

The shape of hemoglobin is affected by CO2/pH, which is important for having high affinity for oxygen in the lungs and lower affinity for oxygen in tissues where a lot of CO2 is released (i.e., where there is a high rate of metabolism).

The shape is also affected by binding oxygen itself: binding oxygen to one subunit causes conformational change in the other subunits of the tetramer, increasing their affinity for oxygen. This is called "cooperative binding."

So, how does any of this relate to CO? Well, it turns out that not only does CO bind very tightly to hemoglobin in the place oxygen would normally bind, taking up space and reducing the capacity for oxygen, it also very strongly increases the affinity of the other subunits for oxygen. It increases the affinity enough that even in the low-oxygen high-CO2 environment of the capillaries, carboxyhemoglobin (hemoglobin bound to CO) continues to hang on to rather than release oxygen. This is represented by a shift in the dissociation curve to the left: oxygen stays bound even when the concentration is low.

This means that fewer CO molecules are necessary to cause deficits in oxygen transport than would be needed if it was only taking up space: one CO molecule binding to a hemoglobin tetramer effectively prevents transport of up to 4 molecules of oxygen.

As a quick caveat, I believe some of the biophysics here are still incompletely understood, so please consider this answer to be an approximation and an explanation of experimental findings to a level of precision sufficient to understand the pathophysiology of CO poisoning. More depth is necessary for a biophysical approach.


Roughton, F. J. W., & Darling, R. C. (1944). The effect of carbon monoxide on the oxyhemoglobin dissociation curve. American Journal of Physiology-Legacy Content, 141(1), 17-31.

Eaton, W. A., Henry, E. R., Hofrichter, J., & Mozzarelli, A. (1999). Is cooperative oxygen binding by hemoglobin really understood?. Nature Structural & Molecular Biology, 6(4), 351.

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  • $\begingroup$ Genuine question, as this is one aspect of Hb I never loved at in my teaching. On the tense/relaxed equilibrium model, can CO be considered as affecting the equilibrium in the opposite direction to hydrogen ions? If so it might be helpful to show that in a diagram. $\endgroup$ – David May 11 at 7:36
  • $\begingroup$ @David Very generally speaking yes that's accurate, but I'm not sure how the other contributors to the TR equilibrium are affected by CO, or how similar or different the states are in terms of actual structure as opposed to O2 affinity. Not really my area of research but my loose understanding is that the TR model is a good but simplified model, similar to other models I'm more familiar with like the HH gating constants for voltage gated channels. $\endgroup$ – Bryan Krause May 11 at 16:12
  • $\begingroup$ @David This paper says that CO stabilizes the R-state and thereby increasing oxygen affinity. However, it would be interesting to see if this shift is simply because of less oxygen per Hb i.e. reduced co-operativity or some active mechanism of R-state stabilization by CO. I could not find any structural biology articles on this topic. $\endgroup$ – WYSIWYG May 13 at 12:52
  • $\begingroup$ @WYSIWYG That makes sense. If CO binds well to the same site as oxygen it would be expected to shift the equilibrium to the R form that binds oxygen (as the poster said, although annoyingly without citation). However the oxygenated Hb is no use to the organism as the effect of CO on the equilibrium prevents or decrease its release. I suppose the point to emphasize is that this occurs where there is a greater concentration of oxygen than CO. $\endgroup$ – David May 13 at 17:23
  • $\begingroup$ @David I think the Eaton paper would be of interest to you. $\endgroup$ – Bryan Krause May 13 at 18:02
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It doesn’t. Carbon monoxide has a higher affinity to hemoglobin (as in, binds better to the protein), that’s why it prevents oxygen from binding to hemoglobin.

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  • $\begingroup$ I would also think this is the case, but could you add sources? $\endgroup$ – AliceD May 10 at 6:59
  • $\begingroup$ This is part of the toxicity of CO but does not answer the OPs question about oxygen dissociation. $\endgroup$ – Bryan Krause May 10 at 14:15
  • $\begingroup$ To be precise CO binds to Fe atom. It is almost a very well known fact in co-ordination chemistry that CO (carbonyl) is a very strong ligand. It can therefore "poison" the metalloproteins by binding to the metal. CO can also poison the mitochondrial enzymes but I guess the toxic effects due to Hb poisoning start acting faster. $\endgroup$ – WYSIWYG May 13 at 12:14

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