Hemoglobin model systems

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Chemical model systems, in particular the picket fence 33 (Figure 10.13), have been particularly useful in the studies on hemoglobin. The small chemical models may be crystallized and their structures determined with far higher precision than the structures of the actual proteins can be. Binding measurements may be made on the models without the complications that arise from the protein structure. The precise displacement of the iron atom from the heme and the geometry of iron-ligand bonds were first measured in the models.29,33,34 The Fe—02 bond is bent, whereas the Fe—CO bond is linear (structures 10.15). The Fe—02 bond is bent at 156° in hemoglobin.35... 

An iron porphyrin is the prosthetic group in the oxygen transport and storage proteins, hemoglobin and myoglobin. Consequently there has been much interest in porphyrin complexes, especially of first row transition metals, as model systems for oxygen transport and storage. Much interest has also been shown in metal porphyrins as models for oxidases, in particular cytochrome P-450. 

The situation for Fe11 porphyrin is rather similar, with the existence of 5 = 0, 1 and 2 states. The iron in Fe(TPP)(THF)2 lies in the plane of the porphyrin.647 This result is of considerable relevance to model systems for hemoglobin and the question of the trigger for the conformational change associated with the cooperative uptake of dioxygen. In this example the presence of a symmetrical weak axial field is the crucial factor. While this particular situation probably does not occur in any natural hemoprotein, these results demonstrate conclusively that high-spin Fe11 will fit into the porphyrin plane. 

Love and Pearson (6) have described a model meat system in which bovine muscle was ground and extracted with distilled, deionized water at 4°C until it was devoid of color, indicating the removal of all meat pigments, i.e., myoglobin and hemoglobin. Other water-soluble components would also be partially or completely extracted by this procedure. The remaining extracted muscle was then used as a model system to which purified myoglobin, ferrous iron and ferric iron were added back to ascertain their role in WOF. 

Because erythrocytes (red blood cells) do not contain any subcellular organelles (they are essentially a membranous sac for carrying hemoglobin) their plasma membrane is a convenient model system for studies of membrane structure as it can readily be isolated from other membranes and intracellular components. One of the major glycoproteins in the plasma membrane of erythrocytes is glycophorin A a 131 amino acid protein that was the first integral protein to be sequenced (see Topic B9). This revealed that the polypeptide chain of glycophorin consists of three domains ... 

Buehler PW, Alayash AI,Toxicities of hemoglobin solutions in search of in vitro and in vivo model systems. Transfusion 2004 44 1516-30. 

The kinetics of misonidazole degradation in a model system (a solution hemoglobin and vitamin C) has been investigated [874], The formed RAs react with molecular oxygen, its superoxide radical anions, having been formed here, and can be the additional reason of the compound toxicity in the presence of oxygen. 

The dioxygen-carrying proteins, hemoglobin and myoglobin, as well as the many synthetic model systems that have been developed recently,44 will not be considered here in this chapter since their chemistry is mainly that of iron in the + 2 oxidation state. The present chapter is therefore restricted to a brief description of the structure and reactivity of some cytochrome and peroxidase proteins. 

The initial step (ultrafast CO loss within 50 fs) of the photodissociation process of CO-ligated iron porphyrin imidazole (Scheme 3), the model system for the CO-Ligated hemoglobin and myoglobin, has been investigated by means of TD-DFT. On the basis of the one-dimensional PEC... 

The combination of metal ion, ligand and chemical environment (sudi as solvent or polymer) determines the chemical and physical properties of the metal dielates. Biological metal porphyrins occuring in hemoglobin, chlorophyll, vitamin B12 and some metallo-enzymes show this extremly well. Model systems seems to be useful in order to elucidate th f ors and to construct artificial systems for practical use. 

Biological cell membranes are mainly made up of lipids and proteins. It is therefore obvious that such mixed model systems should be investigated. Mixed monolayers of hemoglobin, ovalbumin, xanthan, and virus with Mg-(stearate)2 collapsed films have been studied as LB titms on graphite. This provides a means of investigating biopolymers as found in their biological environment in the cell lipid-bilayer medium. 

Model systems for carbonmonoxy (also called carbonyl) hemoglobin show a geometry similar to that of the Fe—C = 0 group, linear or nearly so and essentially perpendicular to the porphyrin plane. " The biochemical literature is littered with reports that this is not the geometry adopted by CO in binding to hemoglobins. We will return to this topic later in this chapter, since the physiological consequences are potentially important. 

In the next section the structures of various derivatives of hemoglobin and its models are presented, and the relationship of structure to ligand-binding properties is examined. Although there is now a wealth of thermodynamic data available from model systems, attention is focused primarily on those for which structural data are also available. 

CO and O2 affinities of a selection of hemoglobins and model systems. Affinities are given as P,/2, and the scale is logarithmic. One order of magnitude corresponds to 1.2 kcal/mol at 25°C-... 

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