Glucuronic acid, detoxification

Phenol O-methyltransferase (POMT) is a membrane-bound methyltransferase that is responsible for the methylation of phenolic compounds that are more commonly recognized as substrates for glucuronic acid or sulfate conjugation (e.g., acetaminophen). Phenol O-methylation is typically regarded as a minor catalytic processes with respect to xenobiotic detoxification. 

Figure 12.2. Interrelationships among Phase I (hydroxylation). Phase II (glucuronic acid, sulfate, and glutathione conjugation), and Phase III (ABC transporter-mediated efflux) detoxification processes leading to the inactivation and elimination of xenobiotics.

Since mutism with olanzapine has been reported in cases of overdose, and detoxification of bilirubin by conjugation with glucuronic acid, the pathway olanzapine uses, is altered in Gilbert s syndrome, which affects 10% of the population, the authors claimed that we should keep in mind idiopathic unconjugated hyperbilirubinemia when prescribing olanzapine. 

Transfer of a glucuronic acid moiety from UDP-glucuronic acid is a common reaction in drug metabolism and detoxification pathways. Spahn (1988) described an assay method that is applicable to arylpropionic acids and is capable of separating and quantitating enantiomers. 

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. 

From the preceding discussion, it is clear that there is very little difference in the type of detoxification reactions used by the different species. One of the major exceptions to this has already been mentioned—the use of glucose instead of glucuronic acid in the... 

Vest, M.F. Rossier, R. (1963) Detoxification in the newborn the ability of the newborn infant to form conjugates with glucuronic acid, glycine, acetate and glutathione. Annals of the New York Academy of Sciences, 111, 183-197. 

---