Mechanism of the cytochrome

The mechanism of the cytochrome P450i4D]y conversion of a C14 methyl sterol into formate and the was studied using 02, and it could be shown that the hydroxyl oxygen atom in the formate that was produced contained one atom of (Shyadehi et al. 1996). 

Korzekwa KR, Trager WF, Nagata K, et al. Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed formation of delta 6-testosterone from testosterone. Drug Metab Dispos 1990 18(6) 974-979. 

Mitchell, P. (1975) Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain protonmotive ubiquinone cycle, FEBS Lett., 56, 1-6. 

Chemical Mechanisms of the Cytochrome P-450 Monooxygenase-Catalyzed Metabolism of Phosphorothionate Triesters... 

Contents Low-molecular-weight organosulfur compounds in nature / Eric Block—Chemical mechanisms of the cytochrome P-450 monooxygenase-catalyzed metabolism of phosphorothionate triesters / R. A. Neal —Sulfur in propesticide action / T. R. Fukuto and M. A. H. Fahmy—[etc.]... 

Figure 1. The Q-cycle mechanism of the cytochrome bc complex (cf. section 1.1). The points of inhibition of three classes of inhibitors are indicated.

Reaction mechanism Based on the observation of reaction intermediates in the crystal structure and on quantum chemical calculations Einsle et al. [148] propose an outline of the first detailed reaction mechanism of the cytochrome c Nir from W. succinogenes. Nitrite reduction starts with a het-erolytic cleavage of the weak N-O bond, which is facilitated by a pronounced backbonding interaction between nitrite and the reduced active site iron. The protons come firom a highly conserved histidine and tyrosine. Elimination of one of both amino acids results in a significant reduced activity. Subsequently, two rapid one-electron reductions lead to a FeNO form and, by protonation, to a HNO adduct. A further two-electron two-proton step leads to hydroxylamine. The iron in the hydroxylamine complex is in the Fe(III) state [149], which is unusual compared to synthetic iron-hydroxylamine complexes where the iron is mainly in the Fe(II) state. Finally, it readily loses water to give the product, ammonia. This presumably dissociates firom the Fe(III) form of the active site, whose re-reduction closes the reaction cycle. 

The same aldehyde is formed in the oxygenation of quadricyclane catalyzed by cytochrome P-450 [88]. The mechanism of the cytochrome P-450-catalyzed reaction has been reported as follows the oxygenation is initiated by one electron transfer from quadricyclane to an electron deficient iron-oxene intermediate, which is followed by insertion of an oxygen atom into a C-C bond rather than a C-H bond. The electron transfer from substrate to the iron-oxene intermediate may be reasonable because of a high ionization potential of quadricyclane. Since the diagnostic aldehyde is a sole product in both sMMO and cytochrome P-450 systems, it is likely that the same reaction mechanism is applicable to these two enzymatic reactions. A plausible mechanism for the sMMO-catalyzed oxygenation of quadricyclane is shown in Scheme 4. 

Cytochrome c did not inactivate hypertensin in the absence of kidney extract. The mechanism of the cytochrome action remains to be explained. 

By the procedure described in the foregoing section, cytochrome a is purified and no other cytochrome components are observed spectro-photometrically, so that the sample is sufficiently pure to investigate the mechanism of the cytochrome oxidase reaction. However, there is sometimes a small absorption shoulder at about 430 m/A. To remove... 

Figure 7. Mechanism of the proton-translocating ubiquinol cytochrome c reductase (complex III) Q cycle. There is a potential difference of up to 150 mV across the hydrophobic core of this complex (potential barrier represented by the vertical broken line). Cytochromes hour and b N are heme groups on the same peptide subunits of complex III which can transfer electrons across the hydrophobic core. The movement of two electrons provides the driving force to transfer two protons from the matrix to the cytosol. Diffusion of UQ and UQHj, which are uncharged, in the hydrophobic core, and lipid bilayer of the inner membrane is not influenced by the membrane potential (see Nicholls and Ferguson, 1992).

Mitchell, P. (1976). Possible molecular mechanisms of the proton motive function of cytochrome systems. J. Theoret. Biol. 62. 327-367. 

Scheme 3. Flavins are capable to undergo both 1 e and 2 e input/output redoxreactions as indicated. Since cytochrome b is a typical 1 e redox reagent, Hemmerich and Schmidt86) suggest a radical mechanism of the sensory transduction (assuming that the cyt b photoreduction is photo-tropically relevant). The nature and fate of the flavin-photosubstrate XH remains obsure. For the case X = cyt b the scheme represents a reversed respiration electron pathway...

J.M. McCord and I. Fridovich, Utility of superoxide dismutase in studying free radical reactions. II. Mechanism of the mediation of cytochrome c reduction by a variety of electron carriers. J. Biol. Chem. 245,1374-1377 (1970). 

Nastainczyk W, Ahr H, Ulrich V, et al. 1982a. The mechanism of the reductive dehalogenation of polyhalogenated compounds by microsomal cytochrome P450. 799-808. 

Jousserandot, A., Boucher, J. L., Henry, Y., Niklaus, B., Clement, B., Mansuy, D., Microsomal cytochrome P450 dependent oxidation of N-hydroxyguanidines, amidoximes, and ket oximes mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides, Biochemistry 37 (1998),... 

Fig. 9.6. Postulated mechanisms in the cytochrome P450 catalyzed reductive denitration of organic nitrates. Pathway a shows the hypothetical mechanism for the reduction of organic nitrates to organic nitrites, whereas Pathway b presents the same reaction for organic nitrites.

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. 

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