Effects of pH and Anions on Functional Properties of Hemoglobin from Lemur fulvus fulvus

Abstract

Abstract Hemoglobin of the prosimian primate Lemur fulvus fulvus is quite similar to human hemoglobin in its primary structure but is significantly different in its functional behaviour. Equilibrium and kinetic studies show that the sequence differences in Lemur hemoglobin do not affect cooperativity, but do produce a decreased oxygen affinity, a decreased Bohr effect, and a decreased response to organic phosphates. The decreased effect of organic phosphates on Lemur hemoglobin may be partially accounted for by the presence of leucine at the β2 position. This constitutes the first experimental verification of the involvement of β2 histidine in 2,3-diphosphoglycerate binding (proposed on the basis of a recent x-ray crystallographic study). The other functional differences cannot be readily accounted for in terms of the current stereochemical model. Tetramers of Lemur hemoglobin have an increased tendency to dissociate into dimers relative to human hemoglobin. In addition, there are greater functional differences between the α and the β chains within tetramers of Lemur hemoglobin than in human hemoglobin tetramers. Kinetic analysis shows that only one type of chain, tentatively identified as β, contributes to the pH dependence of deoxygenation of Lemur hemoglobin. This is the major kinetic expression of the pH dependence of oxygen binding observed in equilibrium studies. Comparative studies show that the exaggerated chain differences and low oxygen affinity of stripped Lemur hemoglobin are closely paralleled by the behavior of human hemoglobin in the presence of saturating amounts of inositol hexaphosphate.