IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 421 



this peptide was shown to be glutathione on the basis of the amino acid 

 composition and of chromatographic and electrophoretic mobihty (]\Iul- 

 ler, 1961). Glutathione is not an integral part of the Hb-Ag molecule, 

 although it is rather stably attached; it is indeed released upon acid or 

 heat denaturation but it is not removed by extensive dialysis (Muller, 

 1961). The type of chemical bond established between glutathione and 

 hemoglobin is not known ; aging of hemoglobin is required to bind gluta- 

 thione, present in high concentration in red cells, to the hemoglobin 

 molecule. The heterogeneity of the Hb-Aj component can possibly be 

 explained by the binding of a different number of glutathione molecules 

 to the hemoglobin molecule. Glutathione has also been found in one of 

 the minor components isolated from cord blood hemogloinn (Muller, 

 1961). Undoubtedly, many instances of heterogeneity of hemoglobins 

 are likely to be explained by similar secondary modifications of the 

 hemoglobin molecule. Environmental factors probably play a decisive 

 role in modifying the hemoglobin molecule. 



F. EMBRYONIC HEMOGLOBIN 



A hemoglobin different from Hb-F has been reported in very early 

 fetuses. This hemoglobin has been designated primitive or embryonic 

 type hemoglobin (Allison, 1955). Drescher and Kiinzer (1954) have 

 reported a hemoglobin with intermediate alkali resistance in human 

 fetuses 7-12 weeks of age. Halbrecht and Klibansky (1956) have re- 

 ported a hemoglobin component with lower electrophoretic mobility than 

 Hb-F, but with an Hb-F type UV spectrum in very early fetuses. 

 Huehns et al. (1961a) have reported two hemoglobins with different 

 electrophoretic mobilities in a survey of human fetus hemoglobins; these 

 components were observed in the smallest fetuses examined, which had 

 a crown-rump measurement of only 3.5 cm. No chemical characterization 

 of these hemoglobins has, however, been reported. 



The evidence for the existence of an embryonic hemoglobin is still 

 unsatisfactory, since it has not been supported by careful chemical 

 investigations. These investigations may rule out the possibility that the 

 hemoglobins observed in very early fetuses correspond to artifacts or 

 that they may in some instances represent genetic variants of Hb-F. 

 It has been suggested by Matsuda et al. (1960), who failed to observe 

 any hemoglobin different from Hb-F in human fetuses, that the "em- 

 biyonic" hemoglobin is an artifact of the deterioration of Hb-F. 



IV. Abnormal Hemoglobins 



Abnormal hemoglobins are defined as the hemoglobins which differ 

 in their physical and chemical properties from the normal components. 



