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RESEARCH PRODUCT

Negative cooperativity in Root-effect hemoglobins: role of heterogeneity.

subject

description

In some animals, the oxygen transport capacity of blood decreases when pH is lowered, yielding oxygen binding curves with Hill-coefficients smaller than unity. This so-called Root effect is observed in several fishes and is important for creating large oxygen partial pressures locally, for example in the swim bladder. While there is general agreement on the physiological advantages of this effect, its molecular basis remains ambiguous. Various studies show that isoforms of hemoglobins usually are present in the hemolymph, when the Root effect is observed. Here, we show that in such a case the mixture of these isoforms can exhibit apparent negative cooperativity, although each component taken separately can be described by the MWC model. In other cases, isolated isoforms exhibit true negative cooperativity. The well established MWC model describes many cooperative phenomena of enzymes and respiratory proteins but is not capable of describing negative cooperativity. In order to model negative cooperativity within a single molecular species a decoupling model might be employed, as pointed out previously. However, simulations show that it is not mandatory to have species with negative cooperativity, in order to obtain the binding curves typically seen for whole blood. These two aspects of the Root effect will be discussed on the basis of data from the literature.