Oxidation-reduction biotransformations

Biotransformation reactions can be classified as phase 1 and phase 11. In phase 1 reactions, dmgs are converted to product by processes of functionalization, including oxidation, reduction, dealkylation, and hydrolysis. Phase 11 or synthetic reactions involve coupling the dmg or its polar metaboHte to endogenous substrates and include methylation, acetylation, and glucuronidation (Table 1). 

Testai E, Gramenzi F, Di Marzio S, et al. 1987. Oxidative and reductive biotransformation of chloroform in mouse liver microsomes. Mechanisms and Models in Toxicology Arch Toxicol Suppl 11 42-44. 

The presence of multiple metabolites in the serum of neonates treated with chloramphenicol suggests that the biotransformation of chloramphenicol takes place by multiple routes to include oxidation, reduction, and conjugation. The presence of particular metabolites does not appear to correlate with toxicity. 

The introduction of fluorine atoms in a molecule can be used to modify the processes and the rates of metabolism of the drug, in order to extend the plasma half-life or avoid the formation of toxic metabolites. Due to the properties of the fluorine atom, in particular its electronic effects, it may interact differently during the biotransformation steps, according to the type of processes involved (oxidative, reductive, hydrolytic, etc), which allow the clearance of the exogen molecule (i.e., the elimination of the active substance from the organism). 

Reductive biotransformation of a contaminant can occur when the contaminant serves as the terminal electron acceptor. Many contaminants that are recalcitrant to bio-oxidation will undergo reductive biotransformations. These biotransformations can lead to detoxification, mineralization, or changes in the mobility of the targeted contaminant. Hexavalent chromium and tetra-chloroethene (PCE) have been investigated as candidates for reductive biotransformation. This technology may be most applicable for in situ remediation for the following scenarios PCE contamination, low-yield aquifers, areas contaminated by both alkylbenzenes and chlorinated ethenes, and deep aquifer contamination. 

Two types of enzymatic pathways, the so-called phase I and phase II pathways, are generally implicated in drug biotransformation. Phase I pathways correspond to functionalization processes, whereas phase II correspond to biosynthetic or conjugative processes. Phase I functionalization processes include oxidation, reduction, hydrolysis, hydration, and isomerization reactions. 

Free metabolites produced by addition, cleavage, oxidation and reduction biotransformations of the parent compound... 

The bio transformation of a chemical is determined by its structure, physicochemical properties, and enzymes in the tissues exposed. Biotransformation can be divided into phase 1 (oxidation, reduction, and hydrolysis) and phase 2 (conjugation). Further metabolism of conjugates has been termed phase 3. 

The chemical reactions involved in drug biotransformation are also classified as either phase I or phase II reactions.27,28 52 60 Phase I reactions consist of those using oxidation, reduction, or hydrolysis. Phase II reactions involve conjugation of the parent drug or the metabolite of a drug that was already metabolized using a phase I reaction. 

Biotransformation refers to changes in xenobiotic compounds as a result of enzyme action. Reactions not mediated by enzymes may also be important. As examples of nonenzymatic transformations, some xenobiotic compounds bond with endogenous biochemical species without an enzyme catalyst, undergo hydrolysis in body fluid media, or undergo oxidation-reduction processes. However, the metabolic phase I and phase II reactions of xenobiotics discussed here are enzymatic. 

Biotransformation or metabolic inactivation of drugs occurs mainly in the liver and, to a lesser extent, in the plasma, kidney, and other tissues, depending on the enzyme system involved. In the liver, microsomal enzymes catalyze many of the metabolic processes involved in the biotransformation of drugs. These metabolic processes may involve nonsynthetic reactions such as oxidation, reduction, or hydrolysis, or synthetic reactions, including conjugation, whereby the drug is coupled with an endogenous substrate (53). 

Biotransformation of non-polar, non-volatile toxicants is a two-phase biochemical reaction. In the first phase (Phase I), the body s enzyme system introduces a polar group into the toxicant (e.g., by oxidation, reduction, or hydrolysis). See Figure 9.28. The enzymes responsible for these transformations are part of a mixed function oxidase system (MFO) of smooth endoplasmatic reticulum present in liver parenchyma cells and in other tissues (e.g., intestine and gill). 

Biotransformation of xenobiotics takes place in two phases. In phase I (= functionalization reactions), reactive groups are either activated or inserted into the substance molecule, thus providing the lipophilic molecule with a functional hydrophilic group. (In phase II, a hydrophilic residue is added to this group transferases hereby catalyze the conjugation with an endogenous substance.) Phase I elfects the insertion of reactive (polar) groups (such as -OH, -COOH, -SH, -NH2) by means of four chemical processes oxidation, reduction, hydrolysis, and hydration. 

Antipyrine is oxidized through biotransformation, independently of perfusion, predominantly in the micro-somes, and is excreted after hydroxylation and conjugation. After oral administration (15 or 18 mg/kg BW, respectively), the metabolic clearance ability of the liver (metabolic capacity of the microsomal monooxygenase system) can be assessed by computation of the concentration curve and the plasma half-life (after 3 and 24 hours). The serum half-life and plasma clearance are significantly enhanced/decreased, depending on the reduction in liver function. There is a close correlation with the galactose elimination capacity as well as with Quick s value. (58-60, 74, 88)... 

The hydroxyl group is present in many asymmetric drugs, natural products, environmental pollutants, etc. In addition, oxidative, reductive, and hydrolytic biotransformations can introduce hydroxyl groups into... 

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