Hemoglobin alpha chain

Figure 2.1S. Absorption spectra of intact (continuous ine) and oxidized (dotted line) hemoglobin alpha chain.

Positive-ion electrospray mass spectrum of human hemoglobin (a) as initially obtained with all the measured masses, and (b) after calculation of true mass, as in Figure 8.3. The spectrum transforms into two main peaks representing the main alpha and beta chains of hemoglobin with accurate masses as given. This transformation is fnlly automated. The letters A, B, C refer to the three chains of hemoglobin. Thus, A13 means the alpha chain with 13 protons added. 

The disease is caused by a mutation of a gene that controls hemoglobin production. A hemoglobin molecule consists of two types of amino acid chains alpha chains and beta chains. At the molecular level, the sickle-cell anemia mutation involves the replacement of one amino acid in the beta chains by another... 

The hemoglobin molecule contains four polypeptide chains and four heme groups. Two of the polypeptide chains, called the alpha chains, are chains of 141 amino-acid residues the other two, called beta chains, are chains of 146 amino-acid residues. In some anemic patients there are abnormal alpha chains or abnormal beta chains, such that the iron atom associated with the abnormal chains is easily converted to the ferric state, losing its power to combine with an oxygen molecule. This sort of anemia is called ferrihemoglobinemia or methemoglobinemia. 

International Hemoglobin Information Center, Variants of the alpha chain, beta chain, delta chain, gamma chain, deleted residues, fusion hemoglobins, extended chains, more than one point deletion. Hemoglobin 9, 229-298 (1985). 

First let us look at an interesting experiment which will only have a phenomenological interpretation until we examine a model of this molecule. We start with ferric hemoglobin A, the oxidized form of the normal hemoglobin that probably all of us have, consisting of two alpha chains... 

Figure 7. EPR spectra of low-spin forms of isolated ferric alpha chains of hemoglobin A...

Three components were found for the hemoglobin (6 Trp residues) and the tetrameric beta subunits (8 Trp residues), while the alpha chain (one Trp residue), its fluorescence decays with two components. What we may conclude from these results ... 

The two fluorescence lifetimes of the Trp residue of alpha chain in hemoglobin could be assigned to two spatial positions of the Trp residue relative to the heme. One of these positions favors energy transfer from the Trp to the heme giving a low fluorescence lifetime in the pieoseeond range. The second position is not in favor of the energy transfer yielding by that a fluoreseenee lifetime in the nanosecond scale. 

Yes. The example in the chapter is myoglobin, which is homologous with the alpha chain of hemoglobin, which is homologous with leghemoglobin. It is easy to understand this if one remembers that most homologous proteins have visibly similar shapes. 

Alpha-Thalassemia A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted, [nih]... 

Albumin alpha(l)-acid glycoprotein Albumin lysozyme ribonuclease a Amyloid precursor protein Beta lactoglobulin Botulinum neurotoxin Erythropoietin Erythropoietin Hemoglobin variants, mouse Hemoglobin variants, human Hemoglobin, globin chains HIV-1 reverse transcriptase Insulin trypsin... 

Hilse, K., and R. A. Popp. 1968. Gene duplication as the basis for amino acid ambiguity in the alpha-chain polypeptides of mouse hemoglobins. Proc. Nat. Acad. Sci. U.S.A., 61 930-936. 

Work on the amino-acid sequences in the polypeptide chains of human hemoglobin was begun in the California Institute of Technology by Dr. Walter Schroeder, and has been continued ever since by him and his associates. The first striking result of this work was the discovery that there are chains of two different kinds in normal adult human hemoglobin, the alpha chain and the beta chain, each doubly represented in the hemoglobin molecule (16). 

In bovine and porcine hemoglobin, sequence val-leu has been found to be N-ter-minal in one of the polypeptide chains. Both hemoglobins therefore contain alpha chains, according to the terminology introduced by Rhinesmith, Schroeder, and Martin.However, the cow alpha chain is different in several respects from the human alpha chain. Although the chains have not yet been separated, the peptide patterns indicate that the alpha chain peptides 5,10, and 17 are absent from bovine patterns, while the alpha chain peptides 12, 13, 18 and an alpha component of spot 16, detected by a positive Sakaguchi test, are present. Although the second chain by definition is not a beta chain, the human beta chain spots... 

The porcine alpha chain may be somewhat more similar to the human alpha chain since the alpha spots 10, 13, and 18 are seen, and the presence of the alpha spots 11, 17, and 23 is suspected. The presence of an alpha-component in the composite spot 15 is likely because of a positive cinnamaldehyde test, and the presence of an alpha-component in the composite spot 16 is indicated by a positive Sakaguchi test. The alpha spot 5 is absent. Among the beta spots, 14 (cinnamaldehyde positive), 26 (Sakaguchi positive), 4, 19, 24, and possibly 25 are present while 12 is absent. Like bovine hemoglobin, porcine hemoglobin does not contain beta chains however, there are a number of tryptic peptides similar to those from the human beta chain observed. 

Schroeder and his associates in Pasadena found that hemoglobin molecules usually consist of four polypeptide chains, two of one kind and two of another kind. The normal adult human hemoglobin molecule contains two alpha chains, which have the sequence val-leu-ser-pro-ala...(total 141 residues), measured from the free-amino end, and two beta chains, which have the sequence val-his-leu-thr-pro-glu-... (total 146 residues). Ingram and Schroeder found that the alpha chains of hemoglobin S are the same as those of hemoglobin A, but the beta chains are different the beta chain of hemoglobin S has valine in the sixth position, in place of glutamate the other 145 residues are the same. 

---