Cytochrome catalysis

Chemical mechanisms of catalysis by cytochromes P-450 towards a unified view. F. P. Guengerich andT. L. Macdonald, Acc. Chem. Res., 1984,17, 9-16 (68). 

Catalysis. Cytochrome P-450 model compounds catalyze the epoxidation of alkenes by hypochlorite ions.16 A typical catalyst is OMn(TMP)L+. 

Cosme J, Johnson EF. Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding. /FtoZ Chem 2000 275 2545-53. 

Li S, LP Wackett (1993) Reductive dehalogenation by cytochrome P450(,j jy[ substrate binding and catalysis. Biochemistry 32 9355-9361. 

Rao, S. B. K., A. M. Tyryshkin et al. (2000). Inhibitory copper binding site on the spinach cytochrome bf complex Implications for Q0 site catalysis. Biochemistry 39 3285-3296. 

It has the heme prosthetic group covalently bonded to protein cytochrome c does not lose its heme catalytic group in these systems, while peroxidases do (catalysis in organic solvents)... 

Recently, a ternary complex of cytochrome c with a polyanionic /1-cyclodextrin has been reported (85). A self-assembled supra-molecular bidentate N,P ligand for aqueous organometallic catalysis was also described (86). Although related, such systems are out of the scope of this review and will not be discussed further here. 

While cytochrome P-450 catalyzes the interaction with substrates, a final step of microsomal enzymatic system, flavoprotein NADPH-cytochrome P-450 reductase catalyzes the electron transfer from NADPH to cytochrome P-450. As is seen from Reaction (1), this enzyme contains one molecule of each of FMN and FAD. It has been suggested [4] that these flavins play different roles in catalysis FAD reacts with NADPH while FMN mediates electron... 

In the field of enzyme catalysis, heme-proteins such as cytochrome P450, for example, exhibit both types of 0-0 bond cleavages in organic hydroperoxides and peroxy acids (178). Heterolytic cleavage of HOOH/ROOH yields H20 or the corresponding alcohol, ROH and a ferryl-oxo intermediate (Scheme 4). Homolytic 0-0 bond cleavage results in the formation of a hydroxyl (HO ) or an alkoxyl (RO ) radical and an iron-bound hydroxyl radical. 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

Vaz ADN, Roberts ES, Coon MJ. Olefin Formation in the oxidative deformylation of aldehydes by cytochrome-P-450—mechanistic implications for catalysis by oxygen-derived peroxide. J Am Chem Soc 1991 113(15) 5886-5887. 

Roberts ES, Vaz AD, Coon MJ. Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism deformylation with olefin formation. Proc Natl Acad Sci USA 1991 88(20) 8963-8966. 

Zhou L, Erickson RR, Hardwick JP, Park SS, Wrighton SA, et al. 1997a. Catalysis of the cysteine conjugation and protein binding of acetaminophen by microsomes from a human lymphoblast line transfected with the cDNAs of various forms of human cytochrome P450. J Pharmacol Exp Ther 281 785-790. 

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