Hemoglobin denaturation

Tesoriere L, Allegra M, D Arpa D et al (2001) Reaction of melatonin with hemoglobin-derived oxoferryl radicals and inhibition of the hydroperoxide-induced hemoglobin denatur-ation in red blood cells. J Pineal Res 31 114-119... 

The accumulation of hydrogen peroxidase affects many intracellular processes and results in hemolysis. These include the cross-linking of membrane proteins hemoglobin denaturation (manifest as Heinz body formation), which in turn affects the physical properties of the erythrocyte and lipid peroxidation, which may affect the cell membrane to cause direct hemolysis (Fig. 11-8). The resultant damage leads to a mixture of intravascular hemolysis and extravascu-lar hemolysis (by which hemolysis occurs in the reticuloendothelial system). In acute hemolytic episodes, the clinical picture is of predominantly intravascular hemolysis, while predominantly extravascular hemolysis is seen in patients with chronic hemolysis. 

Gabay, T., and Ginsburg, H. (1993). Hemoglobin denaturation and iron release in acidified red blood cell lysate - a possible source of iron for intraerythrocytic malaria parasites. 

Dependence of the kinetic constant K] of the met hemoglobin denatur-ation reaction upon isotopic composition of the solvent. Met-hemoglobin concentration M (tetramer) 0.1 M phosphate... 

Dependence of the kinetic constant of met-hemoglobin denaturation reaction upon pH near neutrality. 

The LjD ratio is the relationship between the HC50 and the hemoglobin denaturation index (DI). This ratio is used to predict the potential ocular irritation of these surfactants relating to the SDS compound (L/Z>sds 0.44 irritant). According to the results of the LjD ratio first and by the in vivo eye irritation Draize test later (see Table 2), these linear arginine-based surfactants have no irritant effect in the eyes (non-eye irritants, LjD > 100). 

New ribbon models of proteins for alpha helices, beta-pleated sheets, myoglobin, hemoglobin, denatured protein, prions in mad cow disease, and enzymes are added. 

Denatured globin-ferriheme-HjOz + hemoglobin---------> denatured globin +... 

Winterboum, C. C., and Carrell, R. W., 1974, Studies of hemoglobin denaturation and Heinz body formation in the unstable hemoglobins, /. Clin. Invest. 54 678. 

In an analogous way the influence of alcohol on the kinetics of thermal denaturation of met-hemoglobin was studied successfully144). 

Figure 12, Heat denaturation curves of hemoglobin from three members of a family with Hb-Leslie, a newly discovered unstable variant with a deletion of residue 131 of the p-chain, G.P.Sr. has Hb-Leslie p-thalassemia the %Hb-Leslie is 85% (DEAE-Sephadex chromatography) Gr.P. has Hb-LesUe- Hb-C %Hb--Leslie is 28% M.B. fm Hb LesUe trait %Hb Leslie is 28%,...

The most important product of the hexose monophosphate pathway is reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Another important function of this pathway is to provide ribose for nucleic acid synthesis. In the red blood cell, NADPH is a major reducing agent and serves as a cofactor in the reduction of oxidized glutathione, thereby protecting the cell against oxidative attack. In the syndromes associated with dysfunction of the hexose monophosphate pathway and glutathione metabolism and synthesis, oxidative denaturation of hemoglobin is the major contributor to the hemolytic process. 

Apart from its natural occurrence, Co may find its way into other proteins either adventitiously or deliberately. A study was undertaken where the blood, serum, and plasma of workers occupationally exposed to Co were analyzed for the element.1189 When separated by gel electrophoresis under denaturing conditions, the Co fractions in all blood, serum, and plasma samples showed a similar protein pattern. A variety of proteins of differing size were found to bind Co in fractions collected at pFl 5, whereas only hemoglobin was found in the pH 7 fractions. The conclusions were that in vivo Co is bound to plasma proteins, perhaps albumin and hemoglobin. 

Piper and Fenton [10] indicated that extreme acidity or basicity of the gastric juice denaturalize the enzymatic activity of the pepsin, which shows has a higher activity at a pH = 2. At pH = 5 the enzyme starts to deactivate and at pH= 7, the enzyme irreversibly lose its activity. Fig. 3 shows the pepsin UV-visible spectra before and after interaction with the zeolites while Fig 4 shows the enzymatic activity of the denatured hemoglobin proteolysis versus reaction time. 

Figure 4. Enzymatic activity of the denatured hemoglobin proteolysis vs reaction time with selected samples (samples 5 and 6).

Given that hydroxylamine reacts rapidly with heme proteins and other oxidants to produce NO [53], the hydrolysis of hydroxyurea to hydroxylamine also provides an alternative mechanism of NO formation from hydroxyurea, potentially compatible with the observed clinical increases in NO metabolites during hydroxyurea therapy. Incubation of hydroxyurea with human blood in the presence of urease results in the formation of HbNO [122]. This reaction also produces metHb and the NO metabolites nitrite and nitrate and time course studies show that the HbNO forms quickly and reaches a peak after 15 min [122]. Consistent with earlier reports, the incubation ofhy-droxyurea (10 mM) and blood in the absence of urease or with heat-denatured urease fails to produce HbNO over 2 h and suggests that HbNO formation occurs through the reactions of hemoglobin and hydroxylamine, formed by the urease-mediated hydrolysis of hydroxyurea [122]. Significantly, these results confirm that the kinetics of HbNO formation from the direct reactions of hydroxyurea with any blood component occur too slowly to account for the observed in vivo increase in HbNO and focus future work on the hydrolytic metabolism of hydroxyurea. 

To get from the amino acid analysis of the protein to its structure, its molecular weight had to be estimated. As early as 1885 Zinoffsky had reported a minimum molecular weight for hemoglobin of 16.73 kDa based on its elementary composition and assuming one atom of iron/ mole, a remarkably accurate figure. For most proteins because of their large size and ease of denaturation, classical cryoscopic or ebulliscopic methods were impracticable. Osmotic pressure measurements were... 

Reactive oxygen species react with and denature cellular components, particularly hemoglobin, leading to premature RBC death and hemolysis unless they are reduced by glutathione, which is dependent on NADPH for its regeneration. 

The presence of precipitates of oxidized, denatured hemoglobin (Heinz bodies) helps distinguish the hemolytic anemia caused by of G6PD deficiency from that caused by pyruvate kinase deficiency. 

WOF is a problem associated with the use of precooked meat products such as roasts and steaks. The term WOF was first used by Tims and Watts (2) to describe the rapid development of oxidized flavors in refiigerated cooked meats. Published evidence indicates that the predominant oxidation catalyst is iron from ntyoglobin and hemoglobin, which becomes available following heat denaturation of the protein moiety of these complexes. The oxidation of the lipids results in the formation of low molecular weight components such as aldehydes, adds, ketones and hydrocarbons which may contribute to undesirable flavor. 

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