418 CORRADO UA(;M()N1 



single chains; the changes in the 1I1)-A niolccult's exposed to ])I1 11.6 

 are not reversible and extensive denaturation occurs (Hasserodt and 

 Vinograd. 1959). The dissociation of Hb-F into half-molecules occurs 

 at higher pH's compared to Hb-A; the dissociation is completed at pH 

 11.6 and the Hb-F retains at this pH the spectroscopic characteristics 

 of undcnaturcd hemoglobin for some days (Charhvood et al., 1960). Since 

 denaturation of Hb-A occurs at pH's where the molecule appears to be 

 dissociated into single peptide chains, it may be supposed that Hb-F is 

 more resistant to alkali than Hb-A, because of the di.'ssociation equi- 

 librium of Hl)-F into single chains being shifted toward higher pH's 

 compared to Hb-A. 



The nature of the chemical bonds involved in stabilizing the hemo- 

 globin molecules is not known; it has been suggested that histidines, 

 lysines, and tyrosines provide the active groups involved (Hasserodt 

 and Vinograd, 1959). The different alkali resistance of Hb-A and Hb-F 

 may be due to different chemical bonds established between the peptide 

 chains of these hemoglobins. The higher alkali resistance of Hb-F may 

 not be peculiar of the y chains, but may rather result from the chemical 

 bonds established between the a and y cliains in Hb-F being different 

 from those established between the a and [3 chains in Hb-A. A number 

 of factors are involved in determining the higher alkali resistance of 

 Hb-F; aging of the Hb-F, oxidation of the heme group (Matsuda et al., 

 1960), and exposure to pH 5.0 (Huisman, 1961) are effective in lowering 

 the alkali resistance of Hb-F. Changes of the Hb-F molecule presumably 

 occur under these conditions, which alter the bonds involved in stabi- 

 lizing the quaternary structure of the molecule. 



C. Hb-Ao 



This minor component was first described and isolated by Kunkcl 

 and Wallenius (1955) ; it represents approximately 2.5% of the hemo- 

 globin of normal adults. Hb-Ao is easily separated from Hb-A since it 

 is characterized by an electrophoretic mobility at pH 8.6 considerably 

 lower than that of Hb-A. Hb-A and Hb-Ao have identical molecular 

 weights and UV spectra (Kunkel and Beam, 1957) and very similar 

 amino acid composition (Ingram and Stretton, 1961). Hb-Ao is not a 

 chemical derivative of Hb-A (Kunkcl and Beam, 1957). 



Kunkel et al. (1957) reported that the Hb-A^ level is approximately 

 doubled in thalassemia minor, the heterozygous, nonsymptomatic fonn 

 of the hereditary' anemia known as thalassemia major or Cooley's ane- 

 mia. This observation has been confirmed in a larger number of 

 individuals by other investigators (Ceppellini, 1959a; Silverstroni et al., 

 1957). 



