Cytochrome P-450 Fe

The various redox states of cytochrome P-450 (Fe ", Fe " " RH, Fe " " RH) as well as the metastable oxyferrous compound [(O2—Fe " ") RH] are obtained in ethylene glycol-water mixture their absorption spectra and formation rates are similar to those recorded in pure aqueous media. These identical spectra demonstrate that the intermediates obtained in the mixed solvent at normal and subzero temperatures are similar to those found in the productive enzyme pathway under normal conditions. This is an essential observation since the low-temperature procedure permits one to stabilize and accumulate intermediates and offers the opportunity of obtaining structural information about such intermediates—a result unattainable by classical fast-kinetic techniques. 

Pessayre D, Larrey D, Vitaux J, et al. Formation of an inactive cytochrome P-450 Fe(II)-metabolite complex after administration of troleandomycin in humans. Biochem Pharmacol 1982 31(9) 1699-704. 

Metalloenzymes or metallocoenzymes are involved in a great deal of enzymatic activity, which depends on the presence of metal ions at the active site of the enzyme or in a key coenzyme. Of the latter, the best known is vitamin B12, which contains cobalt. Important metalloenzymes include carboxypeptidase (Zn), alcohol dehydrogenase (Zn), superoxide dismutase (Cu, Zn), urease (Ni), and cytochrome P-450 (Fe). 

Mansuy, D., P. Beaune, T. Cresteil, C. Bacot, J.C. Chottard, and P. Cans (1978). Formation of complexes between microsomal cytochrome P-450-Fe(II) and nitrosoarenes obtained by oxidation of... 

Larrey, D., M. Tinel, and D. Pessayre (1983). Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats. Biochem. Pharmacol. 32, 1487-1493. 

O-insertion from 02 (high-redox potential) Fe Cytochrome P-450... 

Considerably less work has been reported on an electrocatalytic approach to modeling cytochrome P-450 utilizing an electrochemically reduced metalloporphyrin (Fe or Mn) in the presence of... 

Cytochrome P-450 has been characterized in four stable states [Fe, Fe " RH, Fe RH, (O2—Fe ) RH (metastable)] during its oxygenase reaction cycle. In the complete native system a flavoprotein and a redoxin (putidaredoxin) act as electron donors but also as effectors that complement the cytochrome. In the more complex microsomal system the sequence and intermediates are less well defined the electron-transfer chain contains two flavoproteins and one cytochrome, whose interactions with cytochrome P-450 are still the subject of great controversy. 

Fe Cytochrome oxidase reduction of oxygen to water Cytochrome P-450 0-insertion from O2, and detoxification Cytochromes b and c electron transport in respiration and photosynthesis Cytochrome f photosynthetic electron transport Ferredoxin electron transport in photosynthesis and nitrogen fixation Iron-sulfur proteins electron transport in respiration and photosynthesis Nitrate and nitrite reductases reduction to ammonium... 

These generally bind to enzyme that produces them and destroy or inhibit it. For example, olefins and acetylenes bind to nitrogen atoms in the pyrrole part of cytochrome P-450. This may lead to the release of the Fe and destruction of the enzyme. The intermediate can be detected as bound to the enzyme protein or active site. 

Biologically, hydrocarbons are oxidized to alcohols or epoxides by molecular oxygen in the presence of cytochromes P-450, which contain Fe(PPIX) as a prosthetic group coordinated by a cysteinyl mercaptide (Scheme 29). 

The porphyrin-iron(III)-peroxo complex [Fe(TPP)02] (163) was prepared by the reaction of K02 with Fen(TPP) in the presence of a crown ether, and characterized by spectroscopic methods [p(0—O) = 806 cm-1]542. This peroxo complex (163) was found to be inactive toward hydrocarbons. However, addition of excess acetic anhydride to (163) dissolved in a benzene-cyclohexane mixture results in the formation of cyclohexanol and cyclohexanone. This reaction is thought to proceed via acylation of the peroxo group, giving iron percarboxylate (164), which decomposes to an Fev-oxo compound (165) capable of hydroxylating alkanes.543 Such a mechanism has been suggested for the hydroxylation of camphor by Pseudomonas cytochrome P-450.544... 

In relation to enzymic cytochrome P-450 oxidations, catalysis by iron porphyrins has inspired many recent studies.659 663 The use of C6F5IO as oxidant and Fe(TDCPP)Cl as catalyst has resulted in a major improvement in both the yields and the turnover numbers of the epoxidation of alkenes. 59 The Michaelis-Menten kinetic rate, the higher reactivity of alkyl-substituted alkenes compared to that of aryl-substituted alkenes, and the strong inhibition by norbornene in competitive epoxidations suggested that the mechanism shown in Scheme 13 is heterolytic and presumably involves the reversible formation of a four-mernbered Fev-oxametallacyclobutane intermediate.660 Picket-fence porphyrin (TPiVPP)FeCl-imidazole, 02 and [H2+colloidal Pt supported on polyvinylpyrrolidone)] act as an artificial P-450 system in the epoxidation of alkenes.663... 

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