Cytochrome inducers

An oxometalloporphyrin is probably the actual oxidizing agent the threo erythro ratio (35 65) of the diastereomeric sulphoxides obtained from racemic sulphides is close to that obtained for the corresponding oxidation using cytochrome P450 oxidase and differs from that (58 42) obtained by the oxidation using periodate in the absence of the porphyrin [27]. The cytochrome-induced demethylation of N,N-dimethylaniline can also be mimicked with periodate and the metalloporphyrin. 

The Q-cycle hypothesis and other alternative versions of it were attempts to explain the two important reactions occurring during electron transport and proton translocation in the mitochondrial cytochrome be complex and also in the chloroplast cytochrome complex by the so-called oxidant-induced reduction of Cyt b and the interheme electron transport in the Cyts b. Abundant experimental work to obtain evidence for these two reactions as well as other aspects relating to the structure and function of the be complexes has been performed. In addition to what has been mentioned above, we will present several selected examples to elucidate the oxidant-induced reduction of Cvt b and the need for two quinone-binding sites, using the chloroplast CyX-b(f complex or the Cyi-bcx complex from photosynthetic bacteria as examples, all monitored by absorbance changes of cytochromes induced by either steady or flash illumination. 

Both attractive forces and repulsive forces are included in van der Waals interactions. The attractive forces are due primarily to instantaneous dipole-induced dipole interactions that arise because of fluctuations in the electron charge distributions of adjacent nonbonded atoms. Individual van der Waals interactions are weak ones (with stabilization energies of 4.0 to 1.2 kj/mol), but many such interactions occur in a typical protein, and, by sheer force of numbers, they can represent a significant contribution to the stability of a protein. Peter Privalov and George Makhatadze have shown that, for pancreatic ribonuclease A, hen egg white lysozyme, horse heart cytochrome c, and sperm whale myoglobin, van der Waals interactions between tightly packed groups in the interior of the protein are a major contribution to protein stability. 

Anthracyclins. Figure 2 Mechanisms of anthracycline-induced apoptosis of tumor cells. ROS, reactive oxygen species topo II, topoisomerase II cyt c, cytochrome c. 

Mitochondrial permeability transition involves the opening of a larger channel in the inner mitochondrial membrane leading to free radical generation, release of calcium into the cytosol and caspase activation. These alterations in mitochondrial permeability lead eventually to disruption of the respiratory chain and dqDletion of ATP. This in turn leads to release of soluble intramito-chondrial membrane proteins such as cytochrome C and apoptosis-inducing factor, which results in apoptosis. 

Asymmetric oxidation of this sulphide was also catalyzed by two isocytochromes P 450 purified from phenobarbital induced rat liver309. Both P 450 isocytochromes, termed PB-1 and PB-4, when reconstituted with purified rat liver NADPH-cytochrome P 450 reductase and cytochrome b5 afforded ethyl p-tolyl sulphoxide with S-configuration at the sulphur atom. In the case of PB-1 optical purity of this sulphoxide was 58% whereas with PB-4 it was 78%. 

Two main apoptotic pathways have been identified in mammalian cells the extrinsic pathway that is activated by the binding of ligands to cell-surface death receptors, and the intrinsic pathway that involves the mitochondrial release of cytochrome cP The activation of extrinsic and intrinsic apoptotic pathways promotes the cleavage into the active form of the pro-caspase-8 and pro-caspase-9, respectively, that mainly determine the activation of effector caspase-3. ° The intrinsic pathway is the main apoptotic pathway activated by chemotherapeutic drugs, while the cytotoxic drug-induced activation of the extrinsic pathway is a more controversial issue. ... 

Evidence suggests that endosulfan can induce microsomal enzyme activity. Increased liver microsomal cytochrome P-450 activity was observed in male and female rats after single and multiple administrations of endosulfan (Siddiqui et al. 1987a Tyagi et al. 1984). Increased enzyme activity was observed in hepatic and extrahepatic tissues. Based on the increase in aminopyrine-A-demethylase and aniline hydroxylase activity, endosulfan has been shown to be a nonspecific inducer of drug metabolism (Agarwal et al. 1978). 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

Most isoforms of cytochrome P450 are inducible. For instance, the administration of phenobar-bital or of many other drugs causes hypertrophy of the... 

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