Xenobiotic metabolism amino acids, conjugation with

Xenobiotics that contain a free or potential carboxyl group can be metabolized by amino acid conjugation in both plants and animals. This reaction is illustrated by the conjugation of 2,4-D with aspartic acid (Equation 31). In higher plants, amino acid conjugation is... 

With some of the phase 2 metabolizing enzymes, there may be strict ontogenetic patterns of expression. Sulfate conjugation ability occurs early in rats, whereas glucuronidation (of xenobiotics), and conjugation with glutathione and amino acids, only develop over about 30 days from birth. 

Modulation of liver and kidney function. Nutrients and xenobiotics (such as secondary metabolites) are transported to the liver after resorption in the intestine. In the liver, the metabolism of carbohydrates, amino acids, and lipids takes place with the subsequent synthesis of proteins and glycogen. The liver is also the main site for detoxification of xenobiotics. Lipophilic compounds, which are easily resorbed from the diet, are often hydroxylated and then conjugated with a polar, hydrophilic molecule, such as glucuronic acid, sulfate, or amino acids (312). These conjugates, which are more water soluble, are exported via the blood to the kidney, where they are transported into the urine for elimination. 

Rich in both phase I (principally the cytochromes P450, catalyzing hydrolysis, reduction, and oxidation reactions) and phase II (catalyzing conjugation of xenobiotic molecules with hydrophilic moieties) biotransforming enzymes, the liver is the metabolic center of the body. In fact, most of the field of biochemistry is concerned with its metabolic reactions. The liver essentially converts ingested food into a balanced cell culture medium via metabolic interconversion of amino acids, carbohydrates, and lipids and synthesizes many substances that are subsequently exported for use in other areas of... 

Conjugation with amino acids is an important route of Phase 2 metabolism for xenobiotics containing a carboxylic acid functional group. The amino acids involved include glycine, glutamine and taurine (an aminosulfonic... 

Although, as already discussed, aromatic carboxylic acids can be excreted as ester glucosides by many organisms, the major alternative mechanism for metabolizing such xenobiotics is through conjugation with an amino acid. 

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... 

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