Oxidative, Reductive, and Hydrolytic Metabolism of Drugs

The liver metabolizes drugs, other foreign chemical compounds (xenobiotics), and certain endogenous substances (e.g., steroid hormones, bilirubin) by a variety of pathways. They include hepatic microsomal-mediated oxidative reactions, reductive and hydrolytic reactions (phase I), and conjugation (synthetic) reactions with various endogenous substances (phase II) [58,59] j metabolic reactions occur ubiqui-... 

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). 

The hydrolytic and reductive capabilities of microorganisms, especially fungi, are extremely useful in evaluating the metabolic fate of drugs [18-21]. For instance, many pathways of oxidative reactions parallel the same ones in mammals. In addition, fungi have been shown to possess mono-oxygenase enzyme systems... 

Hydrolytic cleavages, along with oxidations, reductions, alkylations, and dealkylations, constitute phase I reactions of drug metabolism. These reactions subsume all metabolic processes apt to alter drug molecules chemically and take place chiefly in the liver. In phase II (synthetic) reactions, conjugation products of either the drug itself or its phase I metabolites are formed, for instance, with glucuronic or sulfuric acid... 

Phase I reactions, which often create anchor points in the xenobiotic molecule for subsequent conjugation, comprise oxidations (electron removal, dehydrogenation and hydroxylation), reductions (electron donation, hydrogenation and removal of oxygen), and hydrolytic reactions. Many metabolic reactions take place in the endoplasmic reticulum of the liver cells. Other organs, particularly kidneys and lungs, also participate in drug metabolism. In addition, a variety of other tissues (brain, skin, intestinal mucosa) have the capacity to metabolize xenobiotics. 

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