Hemoglobin with pyridine

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). 

Dissociation of axial ligands has been followed by picosecond spectroscopy for a number of metalloporphyrins. For the well-known photodissociation of O2 and CO from hemoglobin and myoglobin the photoproducts appear very early < 10 psec. Dissociation of basic axial ligands such as pyridine and piperadine occurs within the lifetime of the excited state for Ni(II), Co(III) as well as for Fe(II) porphyrins. Whether the ejected species is "hot" with energy from the electronic deactivation of the porphyrin is not known, but the dissociation process does not appear to be dependent upon the wavelength of the excitation pulse (30,32). 

Several modifications of protoheme are indicated in Fig. 16-5. To determine which type of heme exists in a particular protein, it is customary to split off the heme by treatment with acetone and hydrochloric acid and to convert it by addition of pyridine to the pyridine hemochrome for spectral analysis. By this means, protoheme was shown to occur in hemoglobin, myoglobin, cytochromes of the b and P450 types, and catalases and many peroxidases. Cytochromes a and a3 contain heme a, while one of the terminal oxidase... 

The pocket is large enough to accommodate ligands such as imidazoles (though these appear to be somewhat different complexes from those seen with myoglobin and hemoglobin), nicotinic acid (pyridine-... 

A recent synthetic model of cobalt-substituted hemoglobin is shown in Scheme 6.1 (245). The long side chain facilitates the coordination of the pyridine ring to the central cobalt atom. The Co(II) complex of this so-called looping-over porphyrin reacts reversibly with molecular oxygen at low temperatures ( —30°C to — 60°C) but the side chain has a negligible en-... 

Hemin as a Prosthetic Group. The cytochromes often are associated with the flavoproteins. They are oxidoreductases because they transfer electrons. Iron is involved in the electron transport by a reversible change of its valency between Fe++ and Fe+++. The cytochromes contain a complex porphyrin system, which is either identical with or closely related to the heme of hemoglobin. Because of their importance, a separate chapter (Chapt. IX) has been devoted to hemo-proteins. The cooperation between pyridine nucleotides and the flavoproteins in the respiratory chain is discussed in Chapt. X-4. 

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