434 CORRAIH) UA(.I.1()M 



tions have Ix'cii located, hut none of these substitutions causes the 

 formation of a stable inetheinoji;lobin l)y forming; an internal complex as 

 the Ilb-M's do. This is the situation also when the substitution involves 

 an amino acid with a reactive side chain, like Hb-Xoi'folk. where an 

 aspartic acid substitutes for the glycine next to the histidine in 

 IIb-]\I„„s,„„ (Baglioni, 19()2a). The reactive side chain of the aspartic 

 acid veiy likely does not point toward the heme group and camiot 

 complex with the iron atom (see Fig. 6). 



In the (3 chain a different Hb-M (MMiiwaukee-i) has been found to 

 have a glutamic acid substituting for a valine in position 67, four resi- 

 dues apart from the histidine in position 63, substituted in Hb-lNIsaskatoon- 

 The side chain of the glutamic acid probably points toward the heme 

 and complexes with the iron atom. 



The abnormal hemoglobin H])-Zui-ich has I'ccently been investigated 

 by ]\Iuller and Kingma (1961); in Hb-Zurich the same histidine substi- 

 tuted by tyrosine in Hb-Msaskatoon is substituted by arginine. In Hb- 

 Zurich apparently there is no interaction between the arginine residue in 

 position 63 and the heme group (see Fig. 7). In order to have an interac- 

 tion the requirement is not only the appropriate geometrical position of 

 a residue in the secondaiy and tertiaiy configurations of the hemoglol)in 

 chain, but also the presence of a reactive side chain. The Hb-Zurich 

 carriers show a puzzling phenomenon: severe hemolytic crisis and inclu- 

 sion bodies in the red cells after sulfanilamide administration (Hitzig 

 et ciL, 1960). The presence of Hb-Zurich appears thus to be associated 

 with a drug-induced inclusion body anemia; this abnormal hemoglobin 

 is presumably altered following sulfanilamide administration, and pre- 

 cipitates, forming inclusion bodies. 



3. The Nucleotide Base Code and the Amr'jio Acid Su})stihitioiis in 

 Abnormal Ilemoqlohins. 



Nirenberg and Matthaei (1962) have recently discovered that poly- 

 uridylic acid directs the synthesis of polyphenylalanine in a cell-free 

 protein-synthesizing system, dependent upon the addition of messenger 

 RNA. This indicated that the nucleotide sequence coding for phenyl- 

 alanine in messenger RNA is made up of uridylic acid only. The effect of 

 randomly ordered polyribonucleotides upon the incorporation of other 

 amino acids has been investigated by Lengyel et al. (1961), by Matthaei 

 et al. (1962), and by Speyer ef al. (1962), in order to determine the 

 composition of RNA coding units. The work of the above-mentioned 

 authors has elucidated the four letter nucleotide code, which specifies 

 the primary sequence of amino acids in proteins. This code is pre- 

 sumably a comma-less, non-overlapping code, as suggested by the 



