Cytochrome catalytic activity

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

For many solubilized enzymes the greatest catalytic activity and/or changes in conformation are found at R < 12, namely, when the competition for the water in the system between surfactant head groups and biopolymers is strong. This emphasizes the importance of the hydration water surrounding the biopolymer on its reactivity and conformation [13], It has been reported that enzymes incorporated in the aqueous polar core of the reversed micelles are protected against denaturation and that the distribution of some proteins, such as chymotrypsine, ribonuclease, and cytochrome c, is well described by a Poisson distribution. The protein state and reactivity were found markedly different from those observed in bulk aqueous solution [178,179],... 

The many redox reactions that take place within a cell make use of metalloproteins with a wide range of electron transfer potentials. To name just a few of their functions, these proteins play key roles in respiration, photosynthesis, and nitrogen fixation. Some of them simply shuttle electrons to or from enzymes that require electron transfer as part of their catalytic activity. In many other cases, a complex enzyme may incorporate its own electron transfer centers. There are three general categories of transition metal redox centers cytochromes, blue copper proteins, and iron-sulfur proteins. 

CcOs from various organisms, as well as CcOs and quinol oxidases, are fairly homologous stmcturally and functionally, and both are distinct from cytochromes ebbs. Most, if not all, CcOs and quinol oxidases require two subunits for catalytic activity (subunits I and II Fig. 18.4), although some, such as mammahan CcO, may contain as many as 11 more subunits of unknown functions [Abramson et al.. 

Only three steps of the proposed mechanism (Fig. 18.20) could not be carried out individually under stoichiometric conditions. At pH 7 and the potential-dependent part of the catalytic wave (>150 mV vs. NHE), the —30 mV/pH dependence of the turnover frequency was observed for both Ee/Cu and Cu-free (Fe-only) forms of catalysts 2, and therefore it requires two reversible electron transfer steps prior to the turnover-determining step (TDS) and one proton transfer step either prior to the TDS or as the TDS. Under these conditions, the resting state of the catalyst was determined to be ferric-aqua/Cu which was in a rapid equilibrium with the fully reduced ferrous-aqua/Cu form (the Fe - and potentials were measured to be within < 20 mV of each other, as they are in cytochrome c oxidase, resulting in a two-electron redox equilibrium). This first redox equilibrium is biased toward the catalytically inactive fully oxidized state at potentials >0.1 V, and therefore it controls the molar fraction of the catalytically active metalloporphyrin. The fully reduced ferrous-aqua/Cu form is also in a rapid equilibrium with the catalytically active 5-coordinate ferrous porphyrin. As a result of these two equilibria, at 150 mV (vs. NHE), only <0.1%... 

The catalytic activity of CYP enzymes requires functional coupling with its redox partners, cytochrome P450 NADPH oxidoreductase (OR) and cytochrome bs. Measurable levels of these two proteins are natively expressed in most cell lines. Therefore, introduction of only the CYP cDNA is generally needed for detectable catalytic activity. However, the levels of expression of the redox partner proteins may not support maximal CYP catalytic activity, and therefore enhancement of OR levels may be desirable. This approach has been used successfully with an adenovirus expression system in LLC-PKi cells [12],... 

Vazquez-Duhalt, R. Semple, K. M. Westlake, D. W. S., and Fedorak, P. M., Effect of Water-Miscible Organic-Solvents on the Catalytic Activity of Cytochrome-C. Enzyme and Microbial Technology, 1993. 15(11) pp. 936-943. 

Although it is still unclear whether the formation of oxidized and hydroxylated products, which is the main pathway of catalytic activities of cytochrome-R-450 reductase, is mediated by free radicals, mitochondrial enzymes are certainly able to produce oxygen radicals as the side products of their reactions. It has been proposed in earlier studies [14,15] that superoxide and hydroxyl radicals (the last in the presence of iron complexes) are formed as a result of the oxidation of reduced NADPH cytochrome-P-450 reductase ... 

The formation of nitric oxide in microsomes results in the inhibition of microsomal reductase activity. It has been found that the inhibitory effect of nitric oxide mainly depend on the interaction with cytochrome P-450. NO reversibly reacts with P-450 isoforms to form the P-450-NO complex, but at the same time it irreversibly inactivates the cytochrome P-450 via the modification of its thiol residues [64]. Incubation of microsomes with nitric oxide causes the inhibition of 20-HETE formation from arachidonic acid [65], the generation of reactive oxygen species [66], and the release of catalytically active iron from ferritin [67],... 

Kennedy, S.W. and Jones, S.P. 1994. Simultaneous measurement of cytochrome P4501A catalytic activity and total protein concentration with a fluorescence plate reader. Anal. Biochem. 222 217. 

Patten CJ, Ning SM, Lu AYH, et al. 1986. Acetone-inducible cytochrome P-450 Purification, catalytic activity, and interaction with cytochrome b5. Arch Biochem Biophys 251 629-638. 

The catalytic activity of cytochrome P450 is not restricted to oxidation. Under certain conditions, especially anaerobic conditions or with certain substrates, it can function as a reductase. For example, P450 can catalyze the reductive removal of halide from polyhalo-genated alkanes such as hexachloroethane or halothane (8,9). 

Bhamre S, Anandatheerathavarada HK, Shankar SK, Boyd MR, Ravindranath V. 1993. Purification of multiple forms of cytochrome P450 from a human brain and reconstitution of catalytic activities. Arch Biochem Biophys 301 251-255. 

Brzezinski MR, Boutelet-Bochan H, Person RE, Fantel AG, Juchau MR. 1999. Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain. J Pharmacol Exp Ther 289 1648-1653. 

Sundin M, Warner M, Haaparanta T, Gustafsson JA. 1987. Isolation and catalytic activity of cytochrome P -450 from ventral prostate of control rats. J Biol Chem 262 12293-12297. 

Tindberg N, Ingelman-Sundberg M. 1996. Expression, catalytic activity, and inducibility of cytochrome P450 2El (CYP2E1) in the rat central nervous system. J Neurochem 67 2066-2073. 

Yang M, Wang L, Xie G, et al. 1993. Effects of intermediate metabolites of 37 xenobiotics on the catalytic activities of reconstituted cytochrome P-45011B1 and P-4501A1 enzyme systems. Biomed Environ Sci 6 8-26. 

Henderson GL, Harkey MR, Gershwin ME et al (1999) Effects of ginseng components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 65 209-214... 

Celander, M. and Forlin, L. (1992). Quantification of cytochrome P450 lAl and catalytic activities in liver microsomes of isosafiol-treated and beta-naphthoflavone-treated rainbow trout Oncorhynchus mykiss). Marine Environmental Research, 34 123-126. 

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