Types of metabolic reactions

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

Examples of toxicologically important species differences in metabolism will therefore be dealt with by considering the different types of metabolic reactions. 

Enzymes are organised into metabolic pathways which collectively constitute metabolism. Two types of metabolism are found in cells, catabolism (breakdown pathways) and anabolism (synthetic pathways). Linking these two types of metabolic reactions are the intermediary reactions of central metabolism. Cells, which contain many complex polymers, thus have the means to generate and convert monomeric materials into the complex biological structure. The sources of these materials are the simpler components from the cell s environment, such as inorganic salts and glucose (Fig. 5.9). 

Recognize the types of metabolic reactions that are common to the functional groups found in drugs... 

As summarized in Figure 7.4, the oxidation of nitrogen, sulfur, and phosphorus is an important type of metabolic reaction in xenobiotic compounds. It can be an important intoxication mechanism... 

Depending on the in vitro technique employed, only certain types of metabolic reactions are possible or require the addition of specific cofactors for reactions to occur. For example, microsomes do not have the ability to form sulfate metabolites due to the lack of both the sulfotransferase enzyme and the necessary cofactor. Table 3 illustrates the metabolic events that are possible within each in vitro system, assuming the necessary cofactors are added in the appropriate concentrations. The location of these enzymes will be important to remember when choosing an in vitro technique to use and which products (metabolites) to expect from each system. 

There are two general types of metabolic reactions, which are known as Phase 1 and Phase 2 reactions. Some drugs undergo both Phase 1 and Phase 2 reactions, but, depending on its chemical nature, it is possible for a drug to be metabolized by either type of reaction only. See Figure 2.4 for possible routes of metabolism of drugs. 

Oxidation Oxidation is the most important and commonest type of metabolic reaction, which involves the addition of oxygen to the drug molecule. 

These enzymes assist in two major types of metabolic reactions of foreign chemicals. The first type, known as Phase I biotransformation, involves only the enzyme and the foreign chemical, and slightly increases the water solubility of that chemical. The second type, known as Phase II biotransformation, requires another chemical known as a cofactor the increase in the water solubility of the chemical caused by these reactions leads to a much higher rate of elimination. 

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