Hemoglobin constant

A 20-year-old anemic man is found to have an abnor mal form of (3-globin (Hemoglobin Constant Spring) that is 172 amino acids long, rather than the 141 found in the normal protein. Which of the following point mutations is consistent with this abnormality ... 

Hemoglobin Constant Spring is commonly found in combination with a -thalassemia especially the —mutation. The clinical presentation of this combination results in a severe form of Hb H disease. 

Unfortunately, hemoglobin forms a complex with carbon monoxide that is considerably more stable than oxyhemoglobin. The equilibrium constant for the reaction... 

Thermodynamically it would be expected that a ligand may not have identical affinity for both receptor conformations. This was an assumption in early formulations of conformational selection. For example, differential affinity for protein conformations was proposed for oxygen binding to hemoglobin [17] and for choline derivatives and nicotinic receptors [18]. Furthermore, assume that these conformations exist in an equilibrium defined by an allosteric constant L (defined as [Ra]/[R-i]) and that a ligand [A] has affinity for both conformations defined by equilibrium association constants Ka and aKa, respectively, for the inactive and active states ... 

Unzai S et al Rate constants for O2 and CO binding to the alpha and beta subunits within the R and T states of human hemoglobin. J Biol Chem 1998 273 23150. 

Hb-Constant Spring (18, 19) was the first variant discovered that has 31 additional residues at the COOH-termlnus of the a-chaln Comparable hemoglobins are Hb-Icarla and Hb-Koya-Dora, and Hb-Tak which has 10 additional residues at the COOH-termlnus... 

A series of enzyme and proteins (met-myoglobin, lysozyme, met-hemoglobin, glucose oxidase, a-chymotrypsin) was also immobilized in a-ZrP by Kumar et al. [134]. Binding constant values clearly confirm the high affinity of the various proteins with the host structure (Table 15.4). 

Upon reaction of 4-nitrosobiphenyl with thiols, its negative Hammett constant (op+ = —0.1855) is expected to facilitate formation of a sulfenamide cation that may delocalize its positive charge partly to C(3), C(2q and C(4/). Hence formation of aminophenols and acid-stable hemoglobin adducts would be conceivable. 

Reversible electron transfer within Mg and Zn-substituted hemoglobin hybrids is initiated by flash photoproduction of the long-lived triplet state ( MP). According to Scheme I, the triplet return to the ground state involves two pathways, intrinsic triplet decay (with rate constant kp) and electron transfer quenching (with rate constant k,). 

The structural stability of mixed-metal hemoglobin hybrids also has allowed us to study low-temperature electron transfer in this system. We first reported the temperature dependence of triplet-state quenching within the [ (ZnP), Fe (H20)P] hybrids, which we attributed to the ZnP Fe P ET reaction [7d]. The rate constant dropped smoothly as the temperature was lowered from room temperature to 200 K. Below this temperature the rate constant remained roughly constant with a tunnelling rate constant of kt 9 s (Fig. 7). 

Metal-substituted hemoglobin hybrids, [MP, Fe " (H20)P] are particularly attractive for the study of long-range electron transfer within protein complexes. Both photoinitiated and thermally activated electron transfer can be studied by flash excitation of Zn- or Mg-substituted complexes. Direct spectroscopic observation of the charge-separated intermediate, [(MP), Fe " P], unambiguously demonstrates photoinitiated ET, and the time course of this ET process indicates the presence of thermal ET. Replacement of the coordinated H2O in the protein containing the ferric heme with anionic ligands (CN , F , Nj ) dramatically lowers the photoinitiated rate constant, k(, but has a relatively minor effect on the thermal rate, kg. 

Activities of the RBC enzymes depend on a constant supply of reduced nicotinamide dinucleotides. Purified hemoglobin is not associated with RBC-like protection because most of the enzymes and cofactors are lost... 

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