Hemoglobin tetramers

Proteins that have more than one peptide chain are called oligomers. The individual chains are called subunits. A protein with a single subunit is called a monomer, one with two subunits is called a dimer, one with three subunits is called a trimer, and one with four subunits is called a tetramer. Hemoglobin is an example of a tetramer. It has two different kinds of subunits and two of each kind. The quaternary structure of hemoglobin is shown in Figure 23.13. 

Gastrointestinal Binding of nitric oxide by tetramer hemoglobin leads to smooth muscle dysfunction and gastrointestinal adverse effects such as abdominal pain, diarrhea, nausea, and vomiting [28, 31 ]. 

Collision Cross Sections (A ) of a P Dimer, a P Dimer, and (a P >2 Tetramer Hemoglobin Species... 

These findings of excess chains in the rabbit reticulocyte, the presence of large numbers of excess chains in / thalassemic reticulocytes (Fessas and Loukopoulos, 1964 Weatherall et al., 1965 Bank and Marks, 1966) and the finding that some 40% of the total hemoglobin in a thalassemia may exist as y8 chain tetramers (hemoglobin H), provide ample evidence that neither nor y8 chains are essential for the release of the other. This evidence is at variance with the model of Colombo and Baglioni (1966) in which yS chains are required for the release of completed chains from the polyribosomes. It is possible that an a or yS chain may facilitate the release of the complementary ehain but neither is essential for release of the other. 

The abihty of iron to exist in two stable oxidation states, ie, the ferrous, Fe ", and ferric, Fe ", states in aqueous solutions, is important to the role of iron as a biocatalyst (79) (see Iron compounds). Although the cytochromes of the electron-transport chain contain porphyrins like hemoglobin and myoglobin, the iron ions therein are involved in oxidation—reduction reactions (78). Catalase is a tetramer containing four atoms of iron peroxidase is a monomer having one atom of iron. The iron in these enzymes also undergoes oxidation and reduction (80). 

In 1982 a study of the usefulness of DBBF in the production of a blood substitute was reported (99). A single modification achieved the dual goals of reduced oxygen affinity and restricted tetramer—dimer dissociation. This work was confirmed in 1987 (98). The product, called aa-hemoglobin, was formulated in Ringer s lactate. P q under physiologic conditions is 3.7 kPa (28.0 torr). Hill s parameter is 2.2, and the Bohr effect was reduced (100). Plasma retention was increased, and the product appeared to be less heterogeneous than some of the other derivatives under study. Its production was scaled up by Baxter Healthcare Corp., under contract to the U.S. Army. 

Hemoglobin is a tetramer built up of two copies each of two different polypeptide chains, a- and (5-globin chains in normal adults. Each of the four chains has the globin fold with a heme pocket. Residue 6 in the p chain is on the surface of a helix A, and it is also on the surface of the tetrameric molecule (Figure 3.13). 

FIGURE 15.23 The myoglobin and hemoglobin molecules. Myoglobin (sperm whale) one polypeptide chain of 153 aa residues (mass = 17.2 kD) has one heme (mass = 652 D) and binds one O9. Hemoglobin (human) four polypeptide chains, two of 141 aa residues (u) and two of 146 residues (/3) mass = 64.45 kD. Each polypeptide has a heme the Hb tetramer binds four O9. (Irving Geis)... 

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

Hemoglobins bind four molecules of Oj per tetramer, one per heme. A molecule of Oj binds to a hemoglobin tetramer more readily if other Oj molecules are already bound (Figure 6-4). Termed cooperative binding, this phenomenon permits hemoglobin to maximize both the quantity of O2 loaded at the PO2 of the lungs and the quantity of O2 released at the PO2 of the peripheral tissues. Gooperative interactions, an exclusive property of multimeric proteins, are critically important to aerobic life. 

The subunit composition of hemoglobin tetramers undergoes complex changes during development. The... 

Myoglobin is monomeric hemoglobin is a tetramer of two subunit types ((X2P2 m HbA). Despite having... 

The 02-binding curve for myoglobin is hyperbolic, but for hemoglobin it is sigmoidal, a consequence of cooperative interactions in the tetramer. Cooperativ-ity maximizes the ability of hemoglobin both to load O2 at the PO2 of the lungs and to deliver O2 at the PO2 of the tissues. 

Preparation of mixed-metal hemoglobin hybrids is achieved by separation of hemoglobin into its constituent a and P chains, followed by demetallation of one of the chains, reconstitution with MP, and chain recombination, yielding the tetrameric [a2(MP), P2(Fe P)] or [a2(Fe P), P2(MP)] species [11]. Thus, MP FeP electron transfer might in principle occur between aj/Pj or ai/P2 subunits. However, the distance between aj and Pj hemes is over 10 A greater than the and P2. This extra distance is expected, and indeed is found, to reduce ET rates by several orders of magnitude. Hence, for all practical purposes we may treat the a2P2 tetramer in terms of two independent [otj, P2] electron transfer complexes. 

Hemoglobin is a tetramer with four polypeptide chains two identical a chains (141 residues) and two identical p chains (146 residues). 

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