Sulfhydryl Groups and the Structure of Hemoglobin by Austen

Hemoglobins possess two very striking properties: they combine reversibly with oxygen, and this binding appears to be autocatalytic. Each molecule of vertebrate hemoglobin possesses four heine groups which combine reversibly with oxygen, and are so associated that the binding of oxygen by one heine greatly enhances the affinity of a second heine for oxygen. Two closely related proposals have been made to explain this interaction. Wyman and Allen (1951) suggest that the large energy of heine-heine interaction is associated with a substantial decrease in entropy produced by structural alterations in the protein accompanying oxygenation. St. George and Pauling (19.51) have found that the a~ni ty of hemoglobin for aikyl isocyarddes depends on the size of the aikyl group (the larger the group the lower the a ~ t y ) , and conclude that the heroes are imbedded in the protein. I t is imagined that oxygenation of one heine loosens the structure so that a second heine can more readily bind oxygen. These properties are entirely dependent upon the specific structure of the protein part of the molecule. Free ferroheme reacts with oxygen, bu t the reaction is not reversible since the ferroheme is at once oxidized to ferriheme. Thus the protein confers stability on the ferrous oxygen complex. Likewise the interaction between, the hemes depends on the specific protein structure. Denaturation by urea produces a large drop in interaction (Wyman, 1948). Furthermore, intact sulfhydryl groups in the protein are essential for hemeheme interaction (P,.iggs, 1952). We wish to report in this paper observations on the effects of several mercurials on hemoglobin which give new insight into the nature of heine-heine interactions and their dependence upon -SH groups of the protein.