Glucuronide, detoxication

Kappus, H., 1986, Overview of enzyme systems involved in bioreduction of drugs and in redox cycling. Biochem. Pharmacol. 35 1-6 Kasper, C.B. and Henton, D., 1980, Glucuronidation. In Enzymatic basis of detoxication. 

Lindroth, R. L. and Batzli, G. 0. (1983). Detoxication of some naturally occuring pheno-lics by prairie voles a rapid assay of glucuronidation metabolim. BiochemicalSystem-atics and Ecology 11,405-409. 

The series of publications from Williams laboratory, entitled Studies in Detoxication, in the Biochemical Journal (London) should be consulted for details of the isolation procedures for many D-glucuronides. 

The enzyme UDP-glucosyltransferase is involved in the detoxication of xeno-biotics. Whereas vertebrates carry out glucuronidation by using UDP-glucuronic acid, invertebrates and plants form the glucoside derivatives with UDP-glucose as the donor of the glucosyl moiety. 

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... 

Metabolism of foreign compounds is not necessarily detoxication. This has already been indicated in examples and will become more apparent later in this book. This may involve activation by a phase 1 or phase 2 pathway or transport to a particular site followed by metabolism. Thus, sulphate conjugation and acetylation may be involved in the metabolic activation of /V-hydroxy aromatic amines, glutathione conjugation may be important in the nephrotoxicity of compounds, methylation in metal toxicity, glucuronidation in the carcinogenicity of /1-naphthylamine and 3, 2 -dimethyl-4-aminobiphenyl. 

In contrast to the enhanced reactivity and toxicity of the various glucuronide, sulfate, acetyl, and glutathione conjugates, amino acid conjugates have not proven to be toxic. It has been proposed that amino acid conjugation is a detoxication pathway tor reactive acyl CoA thioesters. 

The functions of the many and varied plant glycosides are unclear they do not serve as major food reserves or as structural material. Animal cells, particularly in liver and kidney, convert numerous alcohols, amines, and carboxylic acids to 9-glucuronides, which can be transported in the blood and excreted in urine or bile. This is a major route of detoxication of foreign substances. In plants, glucuronides are rare, and glucosides are the predominant sugar derivatives. (See reference 12.)... 

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