Cytochrome reaction with carbon monoxide

Time-resolved resonance Raman studies of the detailed course of cytochrome interaction with carbon monoxide gives an idea of relaxation and conformational changes in the vicinity of the actual reaction site/ A brief conference report lists rate constants for forward and reverse rate constants for interaction of deoxy-hemerythrin with dioxygen, nitrogen monoxide, hydrazoic acid, formamide, and fluoride/ ... 

The reaction of 02 with cytochrome c oxidase to form the oxygenated species A (Fig. 18-11) is very rapid, occurring with apparent lifetime T (Eq. 9-5) of -8-10 is.139 Study of such rapid reactions has depended upon a flow-flash technique developed by Greenwood and Gibson.136/140/141 Fully reduced cytochrome oxidase is allowed to react with carbon monoxide, which binds to the iron in cytochrome a3 just as does 02. In fact, it was the spectroscopic observation that only half of the... 

Spencer and Schaumburg 2000). Although the primary reaction of carbon monoxide is with hemoglobin, it also interacts with myoglobin, cytochromes, and metalloenzymes (e.g., cytochrome c oxidase and cytochrome P450) (WHO 1999). The health importance of these secondary reactions is not well understood. 

Studies of the mammalian cytochromes of the a type have raised at least three problems (1) the identity of cytochromes a and (2) the presence of copper in the cytochrome molecule and (3) the mechanism of oxygen reduction. Again, the preferred theory postulates the existence of two different cytochromes, but this concept is not accepted by all biochemists, and some still believe in a Unitarian theory which postulates that cytochromes a and are actually a single molecule. For example, it was demonstrated that cytochrome a, provided it is in the ferrous form, can also react with carbon monoxide furthermore, the presence of cytochrome c renders cytochrome a autoxi-dizable. Finally, the oxidation of reduced cytochrome Cl requires cytochromes a and c, and the rate of the reaction is optimal if the ratio of a/c is equal to 1. 

In its reduced form, cytochrome P-4S0 combines with carbon monoxide to form a complex having an absorption maximum at 430 mn (Fig. 4) For this reason, the oxidative reactions catalysed by cytochrome P-430 are inhibited by carbon monoxide. Since monochromatic light of 430 nm causes photodissociation of the cytochrome P-430-CO complex, however, strong light of this wave-length partially reverses the inhibition of the oxidative reactions by carbon monoxide. In fact for... 

Cleavage of the oxirane C-0 bond produces a zwitterionic intermediate (Fig. 10.22), which that can undergo chloride shift (Pathway a) to 2,2-dich-loroacetyl chloride (10.90) followed by hydrolysis to 2,2-dichloroacetic acid (10.91). Furthermore, the zwitterionic intermediate reacts with H20 or H30+ (Pathway b) by pH-independent or a H30+-dependent hydrolysis, respectively. The pH-independent pathway only is shown in Fig. 10.22, Pathway b, but the mechanism of the H30+-dependent hydrolysis is comparable. Hydration and loss of Cl, thus, leads to glyoxylyl chloride (10.92), a reactive acyl chloride that is detoxified by H20 to glyoxylic acid (10.93), breaks down to formic acid and carbon monoxide, or reacts with lysine residues to form adducts with proteins and cytochrome P450 [157], There is also evidence for reaction with phosphatidylethanolamine in the membrane. 

Wharton, D. C., and Gibson, Q. H. (1976). Cytochrome oxidase from Pseudomonas aeruginosa. IV. Reaction with oxygen and carbon monoxide. Biochim. Biophys. Acta430, 445-453. 

The most numerous and most complex monooxygenation reactions are those employing a type of heme protein called cytochrome P-450. This cytochrome is usually present in the smooth ER rather than the mitochondria. Like mitochondrial cytochrome oxidase, cytochrome P-450 can react with 02 and bind carbon monoxide, but it can be differentiated from cytochrome oxidase because the carbon monoxide complex of its reduced form absorbs light strongly at 450 ran—thus the name P-450. 

Carbon monoxide reacts with [Fe(TPP)] to form a five-coordinate complex [Fe(TPP)CO], which can be reduced electrochemically to the corresponding iron(I) species from which, however,245 CO spontaneously dissociates. The Fe—CO interaction is stabilized by the,presence of hydrocarbon chains bound by amide linkages to the ortho position of the TPP phenyl rings. Carbon monoxide adducts of iron(I) complexes of a number of these superstructured porphyrins have been reported.245 The chemistry of these highly reduced species is of relevance to understanding240 the reactions of cytochrome P-450 and the peroxidases. 

Conversion of reticuline to salutaridine by rat liver, the critical step that generates the morphine skeleton, was later realized (263), and ambiguities clarified (271). This firmly established that mammalian liver is capable of converting (/ )-reticuline to (-i-)-salutaridine in a coupling reaction which occurs with the help of a microsomal cytochrome P-450 enzyme. The reaction was found to be NADPH dependent and enantiospecific since it did not proceed with (S)-reticuline. The pH optimum was found to be 7.8, and omission of oxygen or NADPH rendered the enzyme complex inactive. Typical inhibitors of P-450 enzymes, as well as exposure to carbon monoxide, halted the formation of (-l-)-salutaridine. These findings, together with a report that intravenous administration of (-l-)salutaridine. 

Cytochrome c peroxidase is reversibly inhibited by ligands that can combine with ferric heme—such as fluoride, azide, and cyanide—but it is not inhibited by carbon monoxide, which indicates that the formation of the ferrous form of the enzyme is not involved in its reaction cycle. The activities of cytochrome c oxidase and cytochrome c peroxidase in tissue may be readily differentiated by the use of carbon monoxide since only the former enzyme is selectively inhibited by carbon monoxide (.19). 

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