Cytochrome P450 oxidases

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 most important group of liver enzymes that are responsible for the oxidative metabolism of most drugs are the microsomal cytochrome P450 oxidases. There are many subtypes (termed isozymes). 

The protease inhibitors are partiaiiy metaboiized by the cytochrome P450 oxidase system and have a potentiai for serious interactions with a large number of commonly prescribed drug products metabolized by the same pathway. 

En route from the intestinal lumen to the general circulation, the ingested substance is broken down enzymatically, e.g., by cytochrome P450 oxidases. 

Gene regulation can be induced or inhibited. Bacteria may Slow become resistant to penicillin because enzymes called /S-lactamases are induced which hydrolyse the crucial /S-lactam ring within the penicillin molecule. Cytochrome P450 oxidases in the liver are induced in response to drug metabolism. 

DNA can also be a target for alkaloids planar and lipophilic alkaloids, such as berberine and sanguinarine (Figure 1.6) are intercalating compounds that assemble between the stacks of paired nucleotides in the DNA double helix [2,3,18,23]. DNA intercalation can disturb replication, DNA repair, and DNA topoisomerases. Frameshift mutations are one of the adverse consequences of intercalating compounds. Some alkaloids, such as pyrrolizidine alkaloids, aristolochic acids, cycasin, and furoquinoline alkaloids, are known to form covalent adducts with DNA bases. Mutations and tumor formation can be the result of such interactions. DNA alkylation occurs in some alkaloids only after activation by liver enzymes, such as cytochrome p450 oxidases (pyrrolizidine alkaloids, aristolochic acids) [17,18,24]. 

As with other HIV-1 protease inhibitors, saquinavir may be associated with drug interactions as a result of the effect of saquinavir on the hepatic cytochrome P450 oxidase system. Although compared with other HIV protease inhibitors, saquinavir has less of an inhibitory effect on cytochrome P450 isozymes clinically relevant interactions can nevertheless occur. Drug interactions with saquinavir have been reviewed (3). 

After absorption, octane is most likely converted to a hydroxy derivative (e.g., alcohol) via the cytochrome P450 oxidase system. 

The justification for these constituents can be seen in the structures of the primary metabolites of fungi. Many metabolic processes utilize phosphates, often with a magnesium ion. It has been estimated that a quarter to a third of all enzymes contain a metal ion as a functional component. Iron is particularly important in the cytochrome P450 oxidases which are involved in the biosynthesis of many fungal metabolites. Other metal ions, particularly zinc, play a... 

Synergistic effects of cytochrome P450 oxidase inhibitors... 

Caffeine (a trimethylxanthine ) is metabolized in the human liver by cytochrome P450 oxidase enzymes, which rip methyl groups off the caffeine molecule, producing three dimethylxanthines called paraxanthine (84%), theobromine (12%) and theophylline (4%) -followed by further demethylation and oxidation, leading to urates and uracil derivatives. 

Toxicological studies have shown that nearly 90% of orally received ethyl carbamate is excreted as carbon dioxide by the action of cytochrome P450 oxidase complex. In the minor pathway, illustrated in Figure 12.40, however, ethyl N-hydroxycarbamate, vinyl carbamate and oxiran-2-yl carbamate arise as minor products. 

El Autunmaline cytochrome P-450 oxidase E2 0-Methylandrocymbine methyl transferase E3 0-Methylandrocymbine cytochrome P450 oxidase [yJeO E4 A-Formyldemecolcine deformylase E5 Colchicine A-acetyl transferase... 

Cytochrome P450 oxidases, cytochrome b5, and NADPH cytochrome P450 reductase are connected with the electron transport chain of the endoplasmic reticulum. This transport chain also represents an important ROS generator. 

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