JEFFRIES WYMAN, JR. 



Such a picture of the intact horse haemoglobin molecule, though 

 somewhat arbitrary, accords remarkably well with conclusions reached 

 by Perutz on the basis of x-ray studies of haemoglobin in the crystalline 

 state, which are discussed in another chapter of this volume. According 

 to Perutz the molecule is a right circular cylinder 34 A high and 57 A 

 in diameter, having a twofold axis of symmetry perpendicular to the 

 cylinder axis and consisting of two structurally and chemically identical 

 halves. The two haems occur in pairs on the surface of the molecule 

 with their planes parallel to one another and to the axis of symmetry 

 and the cylinder axis. However the rectangular model suffers in one 

 respect from the same difficulty as the original Pauling model : it leads 

 to a symmetrical curve of Y vs log p, as indeed does any model in which 

 the haems are all equivalent to one another and the interaction energies 

 are additive. To account for the observed asymmetry we might postulate 

 either that the free energies of interaction in the molecule were not 

 simply additive or that the two identical pairs of haems occupied some 

 arrangement other than a rectangle, which, while satisfying the sym- 

 metry conditions, did not make the individual haems all equivalent. 

 For example this would be so if the four haems were situated at the 

 corners of a parallelogram whose plane was perpendicular to the axis 

 of symmetry. 



Very similar conclusions as to the existence of the haems in pairs of 

 strongly interacting members are suggested by studies of oxidation- 

 reduction phenomena, to which we can only refer hastily. The theory 

 involved is in all essentials identical with that for the oxygen reaction, 

 the n of the oxidation equation being identical in interpretation with 

 the n in equation (6) and the oxidation voltage E corresponding to 

 log p. In the intact molecule the curve of fractional oxidation vs E is 

 asymmetrical with n, as given by the slope of the curve at its mid point, 

 close to 2*. In strong urea solutions the curve becomes exactly sym- 

 metrical with n very nearly equal to 2 though apparently slightly less. 

 Thus here again we have evidence that the haems occur in pairs, with 

 very strong interactions between members of the same pair. In the 

 case of this equilibrium however it appears that there is no significant 

 net interaction between members of different pairs. 



The oxidation behaviour of haemoglobin is to be regarded as a 

 more general instance of the stepwise oxidation illustrated by the two 

 step oxidation of organic molecules such as hydroquinone, which has 

 been studied so extensively by Michaelis. In these molecules, where 

 the intermediate form is known to be a free radical, the interaction 



* This statement is based on experiments by Taylor and Hastings, /. biol. Chem. 131 

 (1942) 649. More recent experiments by R. Havermann, Biochem. Zs. 314 (1943) 118 

 indicate that the curve is symmetrical with n — 1-12. 



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