442 CORH.MX) HACLIOXI 



Huelins and Shooter (1961) have shown by recombination that Hb-Ao 

 dissociated into «..'^ and 8-/'^= subunits and that the ay'' dimors can combine 

 with ^o-^ diniers to give a h('nu)gU)bni ch'cti'ophoi'otically identical to 

 II1)-A. In Di'der to obtain recombination of Ilb-A.., piolongt^l exposure to 

 acid pi I is necessaiy and equilibrium in the exchange of sul)units is not 

 reached after 72 hours. The rate of exchange of Hb-Aj sul)units is con- 

 sidei'ably inci'cased by dissociation in acid buffers of higher ionic 

 strength (Weatherall and Boyer, 19()1). These findings suggest that the 

 chemical bonds between the subunits of Ilb-Ao are proljably different 

 from the ones iin'oh-ed in stabilizing the (luaternary sti'ucture of Hb-A. 



The ways in which the exchange of subunits occurs upon dissociation 

 and recombination merits further experimentation. A conti'adiction exists 

 between the fairly rapid change in molecular weight of the hemoglobin 

 molecule at acid pH and the relatively long time required to reach 

 equilibrium in the exchange of subunits (J. R. Vinograd, personal com- 

 munication). Itano et (d. (1959) considered two possible mechanisms to 

 explain the results of dissociation and reassociation experiments: (1) 

 Hemoglol)in dissociates symmetrically into half-molecules, but only 

 identical half-molecules recombine to re-form the original components; 

 (3) hemoglobin dissociates asymmetrically into pairs of identical chains. 

 Mechanism (2) is in agreement with the recombination experiments, 

 while mechanism (/) would explain the rapid reduction in molecular 

 weight of hemoglobin in acid solutions, which is not followed by recom- 

 bination of subunits. The factors which may prevent aggregation of 

 non-identical half-molecules obtained by symmetric dissociation are not 

 understood at all. We are still far from having a clear-cut explanation 

 of the physicochemical phenomena involved in dissociation and reas- 

 sociation of hemoglobin molecules. 



E. Hb-F VARL\NTS; 



Electrophoretically abnormal fonns of Hb-F luu'e been reported by 

 Fessas and Papaspyrou (1957), by Vella (1959), and by Fessas et al. 

 (1961). These variant forms of Hb-F have not been chemically investi- 

 gated, so that they are still rather undefined. They are thought to have 

 altered y peptide chains; this would prove that the y peptide chain is 

 under independent genetic control. The occurrence of mutant forms of a 

 y chain gene has not been shown experimentally; the existence of this 

 gene is predicted l)y the one gene-one peptide chain hypothesis (Ingram, 

 1959a). 



1. The a Chains of Hb-F 



Minnich et al. (1962) have reported the occui'rence in the cord blood 

 of two Negro babies of a hemoglobin with an electrophoretic mobility 



