Oxidation, reduction, and hydrolysis

The mechanism for the formation of siUca is complex because oxidation, reduction, and hydrolysis pathways are all possible. 

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. 

Over the years, research efforts in biomedical sciences from academia, industry, and government institutions have underpinned a wealth of detailed knowledge regarding metabolism and physiology in humans and vertebrates, and many TK models have been developed. A critical aspect for the development of such models is the identification of the specific enzymes involved in the metabolism of a particular compound. For vertebrates these enzymes are well characterized, at least in terms of structure, if not also in terms of function, but such detailed knowledge is not available for invertebrates. In humans, metabolic routes can be split into phase I, phase II, and renal excretion. However, the relatively recent characterization of transporters such as P-glycoprotein has introduced them in the system as phase 0 or phase III because they can transport the parent compound or the metabolite. Major metabolic routes include phase I enzymes responsible for initial oxidation, reduction, and hydrolysis... 

Fig. 1.—Products Resulting from Periodate Oxidation, Reduction, and Hydrolysis of (1 - 6), (1 - 4), and (1 — 3) Linkages in Dextran.

Oxidation, reduction, and hydrolysis usually produce metabolites which have a reactive functional group. Several of the more common conjugation reactions which mask these functional groups have been mentioned above and are now described in more detail. 

Although the ring system of monocyclic 1,2,3-triazoles shows a remarkable stability towards oxidation, reduction and hydrolysis, under forced conditions thermal extrusion of nitrogen can be achieved at elevated temperatures. Some such reactions are reviewed in (B-76MI41103). Similarly, photochemical extrusion of nitrogen can be effected, and this is consistent with their behavior upon electron impact (cf. Section 4.11.3.2.8). 

Foreign compounds absorbed by mammals are subject to a variety of metabolic processes including functionalization and conjugation, also known as Phase I and Phase II metabolism, respectively. Common Phase I transformations indude oxidation, reduction, and hydrolysis while Phase II metabolism involves the biosynthesis of polar adducts (1). In general the metabolites of foreign compounds are more difficult to identify and quantitate than their parent structures due to their polarity and lower volatility. 

The process of xenobiotic metabolism contains two phases commonly known as Phase I and Phase II. The major reactions included in Phase I are oxidation, reduction, and hydrolysis, as shown in Figure 10.1. Among the representative oxidation reactions are hydroxylation, dealkylation, deamination, and sulfoxide formation, whereas reduction reactions include azo reduction and addition of hydrogen. Such reactions as splitting of ester and amide bonds are common in hydrolysis. During Phase I, a chemical may acquire a reaction group such as OH, NH2, COOH, or SH. 

These reactions are classed as phase I reactions in the overall process of drug metabolism. They generally involve oxidation, reduction, and hydrolysis (Fig. 8.1). 

Reactions of biotransformation of xenobiotics are usually divided into Phase I and Phase II reactions. In Phase I reactions a polar group, such as hydroxyl (-OH), carboxyl (-COOH), thiol (-SH) and amino (-NH2) group, is introduced into the molecule through the reactions of oxidation, reduction and hydrolysis. Metabolites formed can be more toxic than parent compounds (i.e. paraoxon compared to parathion), but some other nontoxic metabolites can be formed as well. In Phase II reactions polar metabolites are conjugated with endogenous substrates such as glucuronides, sulfates, acetates and amino acids, which form hydrosoluble products that can be readily excreted in urine. However, in the case of OPC it is acceptable to divide reactions of biotransformation to activation and detoxication processes. In these metabolic processes significant role have diflerent enzyme... 

The major phase 1 reactions are oxidation, reduction and hydrolysis. 

Biotransformation can be divided into phase 1 (oxidation, reduction and hydrolysis) and phase 2 (conjugation). 

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