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When 2,3-bisphophoglycerate (2,3-BPG) binds to haemoglobin, a higher partial pressure of oxygen is needed to bring about 50% saturation of with oxygen.

What is the physiological significance of this and its molecular basis?

How would this affect the oxygen dissociation curve of haemoglobin and would it alter the Bohr effect?

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In its original form this was a multiple choice question that had remained unanswered for a year, possibly because the detractors are very bad. Because the topic it covers is thought to be of general interest it has been reformulated as a standard question. For the record, the original question asked which of the following were correct: (1) 2,3-BPG in red blood cells causes the oxygen dissociation curve to shift to the left. (2) The binding of 2,3-BPG to haemoglobin lowers the affinity of the haemoglobin for oxygen. (3) Binding of 2,3-BPG to haemoglobin reduces the Bohr effect. (4) When 2,3-BPG is absent, oxy-haemoglobin is less likely to unload oxygen. The ‘correct’ answer was given as (2), but the poster thought that (4) was also correct.

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  • $\begingroup$ What research have you done before asking it here? $\endgroup$
    – another 'Homo sapien'
    Jan 27, 2017 at 11:53
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    $\begingroup$ I've studied oxygen dissociation curves and the Bohr effect; it's just this one question that I don't understand. 2,3BPG obviously shifts the curve to the right and this means that haemoglobin associates with oxygen less easily but dissociates from it more easily. It basically reduces haemoglobin's affinity for oxygen. So if you remove 2,3BPG, the affinity for oxygen should increase and this means that haemoglobin dissociates from the oxygen less easily. I feel that I am missing some very obvious point here so could you please help me. $\endgroup$
    – user29428
    Jan 27, 2017 at 15:28
  • $\begingroup$ I think you're correct. $\endgroup$
    – JM97
    Jan 27, 2017 at 15:55
  • $\begingroup$ No I checked the mark scheme and statement 4 is definitely wrong but I don't know why. $\endgroup$
    – user29428
    Jan 27, 2017 at 16:45
  • $\begingroup$ I have formulated this as a standard question for the reasons explained. I have removed the "homework" tag for this reason and because the original poster will have progressed to other things. I think that although this question overlaps two others, it is unique in addressing the interaction between the Bohr Effect and that of 2,3-BPG, $\endgroup$
    – David
    Jan 28, 2018 at 21:34

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The oxygen dissociation curve for haemoglobin (Hb) in the absence and presence of 2,3-BPG is shown in (i) below: Bohr Effect and 2,3-BPG on Hb It can seen that the curve has shifted to the right (MC-1 incorrect) and the oxygen affinity is obviously decreased, as it takes a higher concentration (pressure) of oxygen to achieve the same percentage saturation (MC-2 correct — and so is option MC-4 as far as I and @JM97 can see, agreeing with the poster. MCQs are an educational abomination!).

The physiological significance of this is considered in detail in my answer to another question, but, in short, it ensures that an adequate proportion of the (smaller) amount oxygen taken up at the lower pressure in the lungs is released in the tissues (3 minus 4, cf. 1ʹ minus 2).

To address the interaction between the effect of 2,3-BPG and the Bohr Effect one needs to consider the corresponding curves for the effect of hydrogen ions (falling pH), shown in (ii), above (see also my detailed answer to this question). It can be seen that the effect of hydrogen ions is similar to that of 2,3-BPG. Can these two have independent (additive) effects? It is known from molecular studies that they both interact with and stabilize deoxy-haemoglobin at different positions (see ii, below), and in one model of the allosteric mechanism they can be considered as shifting the equilibrium from the tense (deoxy-) to the relaxed (oxy-) state of haemoglobin: Tense and relaxed states of Hb (i) Generalized diagram of allosteric equilibrium of tetrameric protein between relaxed state (where it can bind substrate/ligand) and tense state. Negative effectors favour the tense state. (ii) Illustration of this for haemoglobin, where H+ ions protonate His-146 of the β-subunits and 2,3-BPG forms ionic bridges between the two β-subunits.

So it would appear that Bohr effect can still augment the 2,3-BPG effect, but I would imagine that the extent of this augmentation would depend on the initial position of equilibrium, and I would not expect it to be additive — I may be wrong. (Is MC-3 correct or not? A school student can hardly be expected to know unless he had been fed the ‘correct’ answer. Perhaps he is intended to interpret the option as meaning “does the 2,3-BPG effect work in the opposite direction to the Bohr effect”. You may now understand why I loath MCQs.)

Bibliography

The diagrams are my own, based on various sources I have used over the years. To check whether what I have written is correct, the reader may wish to check any of the many accounts online, including the following which have references to original material:

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  • $\begingroup$ I would welcome comments on the question of the additive nature (or otherwise) of the effects of hydrogen ions and 2,3-BPG. There are better enzymologist/protein chemists on this list than me. $\endgroup$
    – David
    Jan 28, 2018 at 21:36

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